Next Article in Journal
A Comparative Analysis of Aroma Profiles of Soju and Other Distilled Spirits from Northeastern Asia
Next Article in Special Issue
Impact of Fermentation of Pumpkin Leaves and Melon Varieties with Lactobacillus Strains on Physicochemical Properties, Antioxidant Activity, and Carotenoid Compounds
Previous Article in Journal
Effect of Litsea cubeba and Cinnamon Essential Oil Nanoemulsion Coatings on the Preservation of Plant-Based Meat Analogs
Previous Article in Special Issue
Okra (Abelmoschus esculentus L.) Flour Integration in Wheat-Based Sourdough: Effect on Nutritional and Technological Quality of Bread
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Bioactive Peptides from Fermented Foods: Production Approaches, Sources, and Potential Health Benefits

Institute of Agricultural Biology and Biotechnology, National Research Council, 56124 Pisa, Italy
*
Author to whom correspondence should be addressed.
Foods 2024, 13(21), 3369; https://doi.org/10.3390/foods13213369
Submission received: 30 September 2024 / Revised: 17 October 2024 / Accepted: 22 October 2024 / Published: 23 October 2024

Abstract

:
Microbial fermentation is a well-known strategy for enhancing the nutraceutical attributes of foods. Among the fermentation outcomes, bioactive peptides (BAPs), short chains of amino acids resulting from proteolytic activity, are emerging as promising components thanks to their bioactivities. Indeed, BAPs offer numerous health benefits, including antimicrobial, antioxidant, antihypertensive, and anti-inflammatory properties. This review focuses on the production of bioactive peptides during the fermentation process, emphasizing how different microbial strains and fermentation conditions influence the quantity and quality of these peptides. Furthermore, it examines the health benefits of BAPs from fermented foods, highlighting their potential in disease prevention and overall health promotion. Additionally, this review addresses the challenges and future directions in this field. This comprehensive overview underscores the promise of fermented foods as sustainable and potent sources of bioactive peptides, with significant implications for developing functional foods and nutraceuticals.

Graphical Abstract

1. Introduction

As consumers are becoming increasingly knowledgeable about health and nutrition, the interest in fermented foods providing a less processed, naturally based, and health-promoting option is growing accordingly [1,2]. The fermentation process consists of a microbial-driven enzymatic transformation of substrates derived from various foods, including dairy products, grains, vegetables, meat, and many others. The microbial activity results in the generation of several products such as amino acids, organic acids, short-chain fatty acids (SCFAs), and bioactive peptides (BAPs), which endow fermented foods with a wide range of bioactivities [3].
BAPs are peptides consisting of 2 to 20 amino acids originating from precursor proteins following an activation process involving multiple reactions such as chemical hydrolysis, enzymatic hydrolysis operated by proteolytic enzymes, or microbial fermentation by proteolytic bacteria [4,5]. The health-promoting potential of BAPs, of either plant or animal origin, has been recognized and linked with several useful bioactivities including antihypertensive, antioxidant, antimicrobial, and anti-inflammatory activities [4,6,7,8]. The most investigated BAPs are those present in milk and dairy products, legumes, cereals, meat, and fish [8].
Owing to their promising properties, research has focused on overcoming the challenges linked with the production and delivery of BAPs. Indeed, fermentation often results in low yields of BAPs, which can be increased by modulating physicochemical parameters such as time, temperature, and pH and using emerging green technologies [9]. Moreover, the stability and bioavailability of BAPs in biological systems can be increased through encapsulation strategies and physicochemical processes [10].
Noteworthily, the attention toward fermentation-produced BAPs has experienced a surge in recent years. As shown in Figure 1, the input ‘bioactive peptides from fermented foods’ generated 375 hits in PubMed, spread between the years 1995 and 2024, and reached a peak of publications in 2021. Thus, an up-to-date review of this relatively new field is offered.
The present review summarizes the available knowledge on BAPs originated in fermented foods, focusing on their generation, sources, and physiological effects and challenges and strategies to enhance their content and delivery. A better understanding of these aspects could open a path toward innovative food products that may contribute to improving human health and nutrition.

2. Fermentation Process for the Synthesis of BAPs

Fermentation is an ancient practice used across several cultures worldwide, from Asia to Europe and the Middle East, to preserve and enhance the nutritional value of foods [11]. This process not only alters the taste, smell, and texture of food but also improves its digestibility and nutritional profile [12]. By breaking down complex carbohydrates and proteins, fermentation increases the intestinal absorption of nutrients, vitamins, and minerals, making them more bioavailable [8,12,13]. Additionally, fermentation lowers the glycemic index of foods thanks to the activity of microbial enzymes such as maltase and α-amylase, which convert starches into simple sugars that are readily absorbed by microorganisms, resulting in a low carbohydrate content in the final product [14].
One of the most exciting outcomes of fermentation is the production of BAPs. These peptides are formed through proteolytic enzymatic reactions, where proteins are hydrolyzed into smaller aminoacidic chains with beneficial health effects [15]. Lactic acid bacteria (LAB) and some fungi such as Aspergillus oryzae are central to this biosynthetic process. The most cited LABs for their effectiveness in producing BAPs are Lactobacillus helveticus, Lactobacillus delbrueckii ssp. bulgaricus, Lactococcus lactis ssp. diacetylactis, L. lactis ssp. cremoris, and Streptococcus salivarius ssp. Thermophilus [16]. In addition to LAB, other microorganisms such as Bacillus species and certain fungi play a significant role in BAP production. For example, Bacillus subtilis and Bacillus licheniformis are known for their robust proteolytic activity, allowing them to hydrolyze proteins into bioactive peptides [17,18]. Fungi such as Aspergillus oryzae, Candida lipolytica, Saccharomyces cerevisiae, and Rhizopus oligosporus, among others, are also extensively used in BAP production due to their variety of enzymes, including protease, capable of breaking down specific types of proteins derived from plants or animals. Fungal strains exhibit a remarkable metabolic diversity, enabling them to utilize diverse carbon and nitrogen sources for the new synthesis of proteins and generation of BAP [19].
LAB species have a highly developed proteolytic system composed of cell envelope proteinases (CEPs), peptide transporters, and intracellular peptidases. CEPs initiate hydrolysis by cleaving proteins into peptides, which are then transported into the cell and further degraded into amino acids by various peptidases [20].
Four types of CEP genes (PrtB, PrtP, PrtR, and PrtH) have been characterized in Lactobacillus species [20,21]. As an example, L. helveticus is highly proteolytic due to the presence of up to four PrtH paralogs with different specificities, making it particularly efficient at generating diverse BAPs [21,22,23]. Several factors, including variations in CEP gene expression, mutations, and specific hydrolysis conditions, influence the variability in BAP profiles among LAB strains [24].
Besides the microbial species, to obtain peptides with enhanced bioactivity, it is crucial to carefully manage the choice of substrate and maintain favorable environmental conditions, including pH and temperature, throughout the fermentation process [8,25]. Additionally, the diversity of animal- and plant-derived proteins plays a significant role in determining the variety of BAPs produced and their bioactivities. For instance, BAP-rich fermented products such as camel milk, Panxian and Spanish dry-cured ham, natto, and tempeh have shown notable health benefits, including antioxidant, antihypertensive, antibacterial, and anti-inflammatory activities [26,27,28,29,30,31].
Microbial fermentation, in general, has emerged as an efficient and cost-effective way of producing BAPs. This process is more convenient compared to conventional enzymatic hydrolysis, being cheaper and simplifying production by avoiding the multiple purification steps through fermentation [32]. However, challenges like low peptide yields and lack of specificity remain obstacles in industrial applications. Ongoing research aims to optimize fermentation conditions, microorganism selection, and substrate management to enhance peptide bioactivity and maximize health benefits [8].

3. Fermented Foods as Sources of BAPs

3.1. Milk and Dairy Products

BAPs in milk play a crucial role in human health [33]. Milk proteins, primarily caseins (α-casein, β-casein, and κ-casein) and whey proteins (β-lactoglobulin, α-lactalbumin, and lactoferrin), are rich in BAPs released during fermentation and digestion [34]. The use of LAB for proteolytic activation enriches milk-derived foods with bioactive compounds [35,36]. Lactobacillus, Lactococcus, and Streptococcus species, and some yeast strains, such as Saccharomyces cerevisiae/paradoxus and Kluyveromyces marxianus, have been identified in fermented dairy products and demonstrate the ability to release BAPs with antioxidant, antihypertensive, and antimicrobial properties [37,38,39].
Ripening and in vitro digestion processes in dairy products like Parmigiano Reggiano (PR) cheese enhance the release of peptides with various health benefits, including antihypertensive, antioxidant, immunomodulatory, anti-inflammatory effects [40]. Similarly, kefir, prepared by adding 4% kefir grains to pasteurized whole milk and fermenting at room temperature for 24 h, led to a 19% inhibition of angiotensin-converting enzyme (ACE) activity and a 37 mmHg reduction in systolic arterial pressure in hypertensive rats [41]. Several studies have shown that milk fermented with L. helveticus is rich in two ACE inhibitory tripeptides, which exert an antihypertensive effect by reducing angiotensin formation [42,43,44]. Peptides derived from lactoferrin, a protein found in the milk of all mammals, have been shown to possess antimicrobial and immunosuppressive properties [45]. Antioxidant and ACE inhibitory peptides have also been identified in donkey milk by multidimensional liquid chromatography and nano high-performance liquid chromatography (HPLC)–high-resolution mass spectrometry [46].
The characteristics of peptides derived from milk can change depending on various factors, such as the hydrolysis method used and the animal producing the milk. For instance, bioactive proteins and peptides with different bioactivities can be achieved from buffalo, camel, goat, sheep, mare, and yak milk [47].

3.2. Meat

Meat and its derivatives are regarded as rich sources of BAPs due to their high protein content. Numerous BAPs have been found in meat and fermented meat products. Mora et al. [48] reported that the fermentation of a dry Spanish sausage, made with 75% lean pork and 25% pork back fat and supplemented with various additives (NaCl, lactose, dextrin, sodium caseinate, glucose, sodium ascorbate, sodium nitrite, and potassium nitrate), inoculated with Lactobacillus pentosus and Staphylococcus carnosus, and ripened in two stages (22 h at 15–20 °C followed by 43 days at 9 °C), generated peptides with ACE-inhibitory activity, such as YQEPLV, YQEPVLGPVR, and YQEPVLGPVRGPFPI, as well as the peptide YQEPVVLGPVRGPFPIIV, which is known for its antimicrobial activity.
Additionally, it was shown that camel meat sausages treated with a range of bacterial strains and cured for up to 28 days exerted a higher peptide concentration and an enhanced antioxidant and antihypertensive capacity compared to non-inoculated sausages, with results being positively affected by the ripening time [49]. The choice of the bacterial species and strain is vital for guaranteeing the best recovery of BAPs from meat, as demonstrated by Takeda et al. [50]. When studying the fermentation of sausages, they found that specific strains of Lactobacillus sakei and Lactobacillus curvatus exerted better proteolysis as well as antioxidant and ACE-inhibitory activities than both the non-treated and the type-strain-treated sausages. Furthermore, the generation of BAPs is also influenced by the kind of meat. For instance, uncured fallow deer sausages had a higher nutritional value than beef sausages, thanks to their greater peptide content, L-carnitine concentration, and antioxidant property [51].

3.3. Plant-Based Foods

Cereals are widely utilized to create novel foods and ingredients due to their high protein content (10–15%), making them a suitable substrate for probiotic fermentation [52]. Cereal proteins can be broken down by microbial enzymes during fermentation, producing BAPs [53]. Recent studies have highlighted the potential of fermented cereal products in improving human health.
Peptides from fermented rice displayed promising results in preventing cognitive decline and promoting brain health in mice by upregulating the levels of brain-derived neurotrophic factor [54]. Fermented oats, when processed with specific microbes like L. plantarum and Rhizopus oryzae, yielded more BAPs and showed higher ACE-I inhibitory activity than unfermented oats, which could be beneficial for hypertension [55]. Additionally, the less studied pseudocereals also benefit from fermentation. For instance, a 72 h solid-state fermentation of quinoa with L. plantarum K779 demonstrated an enhancement in its antioxidant and antihypertensive properties [56]. Likewise, fermenting amaranth using 40 strains of Lactobacillus species as starters at 30 °C for 16 h could potentially lead to the production of the cancer-preventive peptide lunasin [57].
Moreover, fermentation improves the nutritional qualities of legumes such as soybeans and red beans. For example, a solid-state fermentation of soybeans with Bacillus amyloliquefaciens led to a reduction in antinutritional factors and an increase in antioxidant activity [58]. Similarly, solid-state fermentation of red beans with Cordyceps militaris enhanced both protein digestibility and bioactivity [59]. These findings highlight the health benefits of fermented legumes, including their potential in managing conditions like obesity and diabetes.
Overall, microbial fermentation of cereals, pseudocereals, and legumes can significantly enhance their nutritional and functional properties, offering promising health promotion and disease prevention applications.

3.4. Marine Organisms

Fish and shellfish are renowned for their high protein content and are traditionally preserved through salting and fermentation. Fermented fish and shellfish, often used as savory condiments, are processed with starter cultures such as L. plantarum, Lactobacillus brevis, and Bacillus mojavensis [60,61,62].
Recent research has highlighted the bioactive potential of peptides derived from fermented fish and shellfish. For instance, fermentation of Ruditapes philippinarum clams with Bacillus natto for 36 h at 37 °C and pH 7.2 resulted in a peptide with notable ACE-I-inhibitory activity, which remained stable during gastrointestinal digestion. The inhibitory peptide was purified sequentially using ultrafiltration, gel filtration chromatography, and reverse-phase HPLC (RP-HPLC). This peptide not only enhanced nitric oxide (NO) release but also inhibited endothelin-1 secretion and scavenged reactive oxygen species, demonstrating its potential as a pharmaceutical agent [18]. Budu, a Malaysian fermented fish sauce made from anchovy (Ilisha Melastoma) through over 120 days of fermentation, produced BAPs with strong antioxidant properties, such as LDDPVFIH and VAAGRTDAGVH, identified through LC-ESI-TOF analysis. These peptides, rich in hydrophobic and acidic amino acids, are believed to contribute to the high antioxidant activity observed in Budu [63]. Similarly, Pekasam, a traditional Malaysian fermented fish product, was fermented with L. plantarum for 15 days at 27 °C, with a pH range of 4.9 to 5.6. The fermentation process yielded two novel antioxidant peptides, identified by HPLC connected to tandem mass spectrometry (LC/MS/MS), which exhibited significant radical scavenging activity, attributed to their high content of hydrophobic amino acids [64]. Furthermore, commercial Thai fermented shrimp pastes, aged for six months, were found to contain peptides with antioxidant and ACE-I-inhibitory activity, isolated through sequential anion exchange chromatography and solid-phase extraction using a C18 matrix [65].
In another study, Zebra blenny, fermented with Bacillus mojavensis A21 at 37 °C and 200 rpm for 4 to 48 h and then fractionated using Sephadex G-25 gel filtration and RP-HPLC, produced antimicrobial peptides identified by nano ESI-LC–MS/MS. These peptides demonstrated significant antibacterial activity against various pathogens, including Micrococcus luteus and Escherichia coli [62].
Overall, these studies illustrate the significant health benefits of BAPs from fermented fish and shellfish, including antimicrobial, antioxidant, and antihypertensive properties, suggesting their potential use in both food supplements and functional foods.

4. Bioactivities of BAPs Derived from Fermented Foods

BAPs originated in fermented foods perform several biological functions as highlighted by extensive research. In the next sections, the antimicrobial, antihypertensive, antioxidant, and anti-inflammatory activities of different BAPs will be discussed and summarized in Table 1.

4.1. Antimicrobial Activity

Antimicrobial peptides (AMPs) are a kind of BAP present in almost all life forms as part of the innate immune system, being the first defense line against a wide range of pathogens [66]. Most AMPs are characterized by a dominance of β-sheet and α-helix structures, a net positive charge ranging from +2 to +9, and a high proportion of hydrophobic amino acid residues [67]. The positive charge in AMPs is a consequence of the highly represented lysine and arginine residues, which interact with the negatively charged outer membranes of Gram-negative bacteria, leading to membrane perturbation and bacterial cell death [68,69].
In addition to the endogenous ones, AMPs are also derived from fermented foods. A significant example of food-derived AMP production is provided by the bacterium Lactiplantibacillus plantarum, which improves the nutritional quality, organoleptic characteristics, and antioxidant and antimicrobial activities of food, extending its shelf life and reducing the presence of undesirable compounds [70,71]. For instance, camel milk fermented with L. plantarum has demonstrated various health benefits, including antimicrobial, possibly due to the BAPs produced during fermentation [72]. A recent study identified a new low-molecular-weight AMP produced by L. plantarum FB-2, KMY15, which demonstrated a strong ability to inhibit the growth of S. aureus ATCC6538 and E. coli DH5. Furthermore, KMY15 maintained its efficacy against S. aureus ATCC6538, even in the presence of interfering substances such as proteins and lipids in contaminated milk [73]. In another study, antifungal peptides were released after the fermentation of kenaf seed proteins with L. pentosus RK3, identifying eight cationic peptides with molecular weights between 840 and 1876 Da. These peptides showed significant fungicidal activity against Fusarium sp. and Aspergillus niger, with a minimum inhibitory concentration (MIC) of 43 μg/mL and minimum fungicidal concentration (MFC) of 86 μg/mL, thus prolonging the latency phase of the fungi and increasing their membrane permeability [74]. All this evidence demonstrates the potential of AMPs as an alternative to traditional antibiotics due to their versatility, wide spectrum of activity, and the possibility of being modified to optimize their efficacy and stability under different conditions [75].

4.2. Antihypertensive Activity

ACE inhibitors work by blocking the enzyme ACE that converts angiotensin I into angiotensin II, a peptide that causes blood vessels to tighten. When angiotensin II is overproduced, it can lead to high blood pressure, which is a common problem in people with hypertension. Hypertension, characterized by persistently elevated blood pressure above 140/90 mmHg, is a prevalent risk factor associated with strokes and cardiovascular disease [76]. For this reason, ACE inhibitors are considered crucial for controlling blood pressure in hypertensive patients [77,78].
Recently, BAPs derived from food proteins have attracted significant interest as natural ACE inhibitors, offering a viable alternative to synthetic drugs, which often present relevant side effects [79]. Several ACE-inhibitory peptides (ACEIPs) have been isolated from fermented foods such as dairy products and vegetables [31,80,81,82,83]. In general, ACEIPs have similar primary structures, often featuring proline, tyrosine, cysteine, histidine, tryptophan, and methionine at the C-terminus, a factor that enhances their ACE inhibitory activity [84,85]. Moreover, the ACE active site contains a zinc coordination site and a hydrophobic pocket that allows interaction with aromatic residues, enhancing the binding of inhibitory peptides that contain them [86].
BAPs with all these features show strong ACE-inhibitory potential. They are likely absorbed by specific transporters across the intestinal epithelial wall, remain intact through gastrointestinal digestion, and maintain their ACE-inhibitory activities [87,88]. For instance, oral administration of the BAPs EAPLNPKANR and IVG, isolated from Cangkuk, a traditional Indonesian fermented beef, reduced blood pressure in spontaneously hypertensive rats 8 h after administration. The greatest effect was observed with IVG, due to its smaller size and the presence of isoleucine at the N-terminal, which facilitates its entry and binding to the active sites of ACE, thereby inhibiting the formation of angiotensin II and lowering blood pressure [89].
Among ACEIPs, the VPP (Valine–Proline–Proline) and IPP (Isoleucine–Proline–Proline) peptides have been extensively studied thanks to their potent ACE-inhibitory and pressure-lowering ability. These peptides were originally derived from the fermentation activity of bacteria like L. helveticus and yeasts like Saccharomyces cerevisiae in fermented milk and have since been demonstrated to yield marked antihypertensive activity in animal studies [90]. Additionally, clinical trials have shown that daily consumption of VPP/IPP tablets (10.2 mg/day) for 4 weeks decreased blood pressure levels and arterial stiffness in patients affected by metabolic syndrome [91]. Moreover, Moayedi et al. [92] used Bacillus subtilis to ferment tomato seeds and generate BAPs. Among the produced BAPs, the hexapeptide DGVVYY exhibited the strongest ACE-inhibitory activity, achieving an IC50 value of 2 µM.

4.3. Antioxidant Activity

BAPs derived from fermented foods have shown promising antioxidant activity by neutralizing reactive oxygen species (ROS) such as superoxide anions and hydroxyl radicals [93]. The body’s enzymatic and non-enzymatic antioxidant systems effectively neutralize harmful free radicals. However, environmental stress, lifestyle, and disease can disrupt this balance, leading to oxidative stress. This imbalance is associated with cell apoptosis and various diseases, including diabetes, atherosclerosis, and cancer [94].
It has been shown that BAPs can scavenge free radicals, reduce lipid peroxidation, and chelate metal ions, which helps prevent oxidative damage [30,95]. Their antioxidant properties are closely linked to their aminoacidic composition. For instance, peptides rich in hydrophobic amino acids have been observed to interact more effectively with cell membranes, thereby enhancing their antioxidant effects [96]. An example is represented by the peptide VLPVPQK from cheddar cheese fermented with L. helveticus, which contains proline residues at the N-terminus, exhibiting an antioxidant capacity of 5.71 ± 0.59 mmol of Trolox equivalents/mg in a Trolox equivalent antioxidant capacity (TEAC) assay [97]. Furthermore, pre-treatment of rat fibroblast cells with this peptide, followed by induction of oxidative stress, suppressed ROS production and increased antioxidant enzymes [98]. Another example is the peptide SNLCRPCG, derived from chicken feathers fermented with Bacillus subtilis, which exhibited strong antioxidant activity due to its hydrophobic amino acids and cysteine’s thiol (-SH) groups [99].
Furthermore, BAPs were found to modulate the antioxidant response by interacting with cellular signaling pathways. For instance, novel antioxidant peptides like LY-4, LP-5, and VL-9, identified from fermented broad bean paste, have been shown to activate the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, protecting liver cells (HepG2) from oxidative stress induced by 2,2′-Azobis(2-amidinopropane) dihydrochloride (AAPH), a radical generator [100]. Similarly, casein hydrolysate produced by Lactobacillus reuteri has been identified for its strong antioxidant potential, with the peptide VKEAMAPK showing significant effects by noncompetitively inhibiting Keap1, thereby activating the Nrf2 pathway, an essential protection mechanism against oxidative damage [101].
In another study, tomato seeds fermented with Bacillus subtilis produced antioxidant peptides such as GQVPP, which achieved a 97% 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity at 0.4 mM, demonstrating its potential in reducing oxidative stress [92]. A peptide fraction with antioxidant activity was isolated and purified from whey protein metabolites fermented by Lactobacillus rhamnosus B2-1. The final purified peptide, B11, showed significant antioxidant activity, with a 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical scavenging rate of 84.36%, a hydroxyl radical scavenging rate of 62.43%, and an oxygen radical absorbance capacity (ORAC) activity of 1726.44 μM Trolox equivalent/g. With an amino acid composition of 51.42%, dominated by glutamic and aspartic acids, B11 appears promising for food-based applications [102].
These findings highlight the diverse antioxidant mechanisms and health benefits of BAPs derived from fermented foods, making them promising natural alternatives to synthetic antioxidants.

4.4. Anti-Inflammatory Activity

The production of various immunomodulatory peptides with anti-inflammatory properties is facilitated by fermentation. They play a significant role in regulating immune response by modulating key interleukins such as IL-4 and IL-10 (anti-inflammatory), IL-1β and IL-2 (proinflammatory), IL-6 that can act as either, and cytokines such as tumor necrosis factor α (TNF-α) [103]. For instance, the hydrolysis of casein by the PrtB protease from Lactobacillus. delbrueckii subsp. bulgaricus 92,059 produced BAPs, which demonstrated immunomodulatory and anti-inflammatory effects in an in vitro assay of TNF-α-induced nuclear factor-κB (NF-κB) activation at concentrations of 5 mg/mL and 2.5 mg/mL, respectively [104]. Peptides from Xuanwei dry-cured ham have been found to reduce IL-6 and TNF-α levels in mice with dextran sodium sulfate-induced colitis, alleviating inflammatory bowel disease symptoms [105]. Moreover, soybean peptides have demonstrated beneficial effects in reducing LPS-induced intestinal inflammation in IEC-6 intestinal epithelial cells by decreasing NO production and downregulating the expression of inflammatory mediators, such as IL-1β, IL-6, and TNF-α [106].
Peptides with anti-inflammatory properties often feature positively charged and hydrophobic amino acids, especially at the C- and N-termini [107,108]. This structural composition facilitates their interaction with cell membranes and bacterial lipopolysaccharide (LPS), which is released from the wall of Gram-negative bacteria during infection and triggers inflammatory cytokines. However, the BAP’s N-terminal region can block the release of LPS, thus stopping the inflammatory response. In a study where L. plantarum A3 and L. rhamnosus ATCC7469 were used to ferment broccoli, 17 novel anti-inflammatory peptides were identified, including GDRW, KASFAFAGL, FGDFNPGGRL, and ADLAHLPF, rich in hydrophobic amino acids, and HFKQPW, RFR, and KWR, with positively charged amino acid residues [109].
Table 1. Summary of BAP release under specific fermentation conditions and their bioactivity.
Table 1. Summary of BAP release under specific fermentation conditions and their bioactivity.
Fermented FoodMicroorganismsFermentation ConditionsPeptide SequenceBioactivityReferences
MilkL. plantarum FB-237 °C for 20 hKMYKKGRLWLVAGLSAntimicrobial
S. aureus and L. monocytogenes
MIC = 256 μg/mL
E. coli MIC = 128 μg/mL
[73]
MilkL. helveticus CP790 and Saccharomyces cerevisiae37 °C for 24 hVPP
IPP
ACE-I
IC50 = 9 μM
IC50 = 5 μM
[110]
MilkLacticaseibacillus rhamnosus NCDC24Not specifiedAGWNIPM,
ALPMHIR,
VLPVPQKA YLGYLEQLLR
Antioxidant
ABTS+ radical scavenging activity
from 73.45 ± 0.57 (100 µg/mL)
to 1.44 ± 0.22 (10 µg/mL)
[111]
Miso pasteAspergillus oryzae30 °C for 40 hVPP, IPPAntihypertensive[112]
MilkBifidobacterium bifidum MF20/537 °C for 48 hVLPVPQK
LVYPFP
Antioxidant
ACE-I
IC50 = 132 μM
[113]
Sator bean (Parkia speciosa)L. fermentum ATCC933837 °C for 8 daysEAKPSFYLK
PVNNNAWAYATNFVPGK
Antioxidant
DPPH activity = 78.48 ± 3.16%
Antibacterial activity
S. typhi (73.41 ± 0.08%) and
S. aureus (64.70 ± 1.10%)
[114]
Skimmed milkEnterococcus faecalis CECT 572730 °C for 48 hLHLPLPAntihypertensive
IC50 = 59.6 μg/mL
[115]
Dry fermented
sausage
L. pentosus and Staphylococcus carnosusTwo stages: 20 °C for 22 h;
9 °C for 43 days
YQEPVLGPVR,
YQEPVLGPVRGPFPI,
YQEPLV
ACE-I
IC50 = 300 µM
[48]
Avena (Avena sativa L.)L. plantarum B1-6 and Rhizopus oryzae30 °C for 72 hNot specifiedACE-I
IC50 = 0.42 mg
protein/mL
[55]
Lupin, quinoa, and wheatL. reuteri K777 and L. plantarum K77935 °C for 72 hNot specifiedACE-I
from 25.3% to 58.9%
Antioxidant
DPPH radical scavenging activities from 25.0% to 65.0%
Antiproliferative
[56]
Wheat, soybean,
Barley, and
amaranth
L. curvatus SAL33 and L. brevis AM730 °C for 16 hLunasin (SKWQHQQDSCRKQLQGVNLTPCEKHIMEKIQGRGDDDDDDDDD)Cancer preventive[57]
BuduNot specifiedOver 120 daysVAAGRTDAGVH
LDDPVFIH
Antioxidant
DPPH radical scavenging activity
IC50 = 1.451 ± 0.873 (mg/mL)
IC50 = 0.844 ± 0.203 (mg/mL)
[63]
Zebra blenny (Salaria basilisca) muscle
protein
Bacillus mojavensis A21From 4 to 48 h at 37 °CGLPPYPYAG, LVDGLDVGIL,
ETPGGTPLAPEPD, LSYEEAITTY, HHPDDFNPSVH
Antibacterial
E. coli MIC = 0.62 ± 0.01 mg/mL
K. pneumoniae MIC = 1.23 ± 0.02 mg/mL ACE-I
Antioxidant
[62]
Pekasan (Loma fish)L. plantarum IFRPD P152 weeks at RTAIPPHPYP
IAEVFLITDPK
Antioxidant activity
DPPH radical scavenging activity IC50 (mg/mL) = 1.38 ± 0.25
IC50 (mg/mL) = 0.897 ± 0.84
[64]
Manila clam (Ruditapes philippinarum)Bacillus natto37 °C for 36 hVISDEDGVTHACE-I
IC50 = 8.16 μM
[18]
Thai shrimp pastesNot specifiedNot specifiedSV,
IF,
WP
ACE-I
IC50 = 60.68 ± 1.06 μM
Antioxidant
ABTS+ EC50 = 17.52 ± 0.46 μM
[65]
Kenaf seedL. casei37 °C for 72 hAKVGLKPGGFFVLK,
GSTIK, LLLSK, TAHDDYK
Antibacterial activity
from 42.07% to 77.38%
[116]
Tomato waste
proteins
Bacillus subtilis37 °C for 24 hDGVVYY
GQVPP
ACE-I
IC50 = 2 µM
Antioxidant
97% DPPH scavenging activity
at 0.4 mM
[92]
Cheddar cheeseL. helveticus and
Streptococcus thermophilus
Not specifiedEMPFPK, AVPYPQR,
VLPVPQK, AMKPWIQPK
Antioxidant
TEAC = 5.7 ± 0.6 mmol TE/mg
[97]
Feather hydrolysateBacillus subtilis S1-437 °C for 72 hSNLCRPCGAntioxidant
DPPH IC50 = 0.39 mg/mL
[99]
Whey proteinL. rhamnosus B2-137 °C for 48 hB11Antioxidant
ABTS+ radical scavenging activities = 84.36%
[102]
CaseinL. reuteriNot specifiedVKEAMAPKAntioxidant
Decreased ROS activity by 45%
[101]
BroccoliL. plantarum A3 and L. rhamnosus ATCC746937 °C for 24 hSIWYGPDRPAnti-inflammatory
Inhibits NO release from inflammatory cells at 25 µM, with an inhibition
rate of 52.32 ± 1.48
[109]
RT: room temperature. ACE-I: angiotensin-converting enzyme-inhibitory activity. TEAC: Trolox equivalent antioxidant capacity. ROS: reactive oxygen species. Each letter in the peptide sequence corresponds to an amino acid: A = alanine, C = cysteine, D = aspartic acid, E = glutamic acid, F = phenylalanine, G = glycine, H = histidine, I = isoleucine, K = lysine, L = leucine, M = methionine, N = asparagine, P = proline, Q = glutamine, R = arginine, S = serine, T = threonine, V = valine, W = tryptophan, Y = tyrosine.

5. Challenges and Limitations in BAPs Production

The development of BAPs is a promising yet challenging area in biotechnology, with potential applications across the food, nutraceutical, and pharmaceutical industries. However, several significant obstacles impede their efficient development and commercialization. One of the foremost challenges in developing BAPs is the scalability of production processes. In microbial fermentation, issues like longer reaction times and low yield of peptide formation pose additional barriers. The complex proteolytic systems in different microorganisms result in variations in peptide structures, making it difficult to standardize production processes [24]. Even among the same species of bacteria, such as Lactobacillus or Bacillus, differences in proteolytic capabilities can result in different peptide profiles when exposed to the same substrates [117]. While enzymatic hydrolysis offers more controlled conditions, microbial fermentation involves a longer reaction time and greater unpredictability in the peptides generated. Factors such as the type of microorganism, the protein substrate used, fermentation time, and environmental conditions (e.g., pH, temperature, and oxygen levels) all impact the extent and specificity of hydrolysis [118].
Additionally, the purification of BAPs from fermented mixtures is technically demanding and costly. Microbial fermentation typically yields a complex mixture of peptides, alongside other microbial by-products such as exopolysaccharides, bacteriocins, and dead microbial cells. These additional compounds can interfere with the isolation of pure BAPs and complicate the identification of the specific bioactive properties of the peptides [119]. Purification processes are essential to isolate peptides with specific biological activities, yet they are time-consuming and costly. Ultrafiltration and chromatographic techniques, such as HPLC, are commonly used but are often not suitable for large-scale production due to issues like membrane fouling and poor reproducibility [120]. Once produced and purified, BAPs face challenges related to their stability and bioavailability, covered in depth in Section 6.
Furthermore, regulatory approval and clinical validation hinder the production of BAPs through microbial fermentation. Despite the promising bioactivities demonstrated in in vitro and animal studies, there is a lack of well-designed clinical trials to confirm the efficacy of food-derived peptides in humans [121]. Regulatory agencies, such as the European Food Safety Authority (EFSA), require rigorous evidence of the safety and efficacy of functional food ingredients before they can be marketed. Without sufficient clinical evidence, it is difficult for companies to commercialize BAPs or make health claims about their benefits, which hinders their marketability [5]. Therefore, addressing these issues is critical for the future success of BAPs in the health and wellness industries.

6. Approaches for Enhancing BAP Production, Stability, and Bioavailability

Since the fermentation process often results in low yields of BAPs, besides modulating physicochemical parameters such as temperature, pH, and time, emerging green technologies and encapsulation strategies have been employed to enhance BAP content, stability, and bioavailability. Figure 2 summarizes BAP production techniques, stability/bioavailability approaches, and the major mechanisms responsible for BAP biological activity.

6.1. Strategies to Optimize the Production of BAPs in Fermented Foods

Microbial fermentation has been extensively used to improve the nutritional quality and health-promoting properties of various foodstuffs, for instance, by increasing the availability of BAPs. However, despite being economical and easy to perform, fermentation displays low yields of BAP production, a factor that limits its industrial escalation [9,122]. Thus, several strategies have been attempted to promote protein hydrolysis and increase the recovery of BAPs.
One such way consists of exposing the food matrix to ultrasounds, microwaves, or high pressure before the fermentation process [9,122]. In a study performed by Munir and colleagues [123], Cheddar cheese was produced with milk pre-treated by either ultrasonication, high-pressure processing, or microwave, and its antioxidant and ACE-inhibitory activities were followed during ripening.
It was revealed that the pre-processing steps increased the rate of proteolysis during cheese making and ripening, as well as the antioxidant and ACE-inhibitory activities of the resulting cheese, with the best results obtained with ultrasonication. Additionally, moderate ultrasound exposure during fermentation has been proven to affect the activity of microorganisms, as testified by the work of Xie et al. [124]. Indeed, they showed that ultrasound-assisted fermentation of okra improved its peptide and soluble protein contents, enhancing its antioxidant properties.
Finally, the food matrix can also be processed after fermentation to increase the yield of BAPs. As an example, milk fermented with Lactobacillus delbrueckii QS306 and subjected to ultrahigh-pressure treatment exerted a higher peptide concentration and variety, and an increased ACE-inhibitory activity compared to the non-processed sample [125].
Another strategy to enhance BAP yield is to optimize the fermentation parameters, including incubation time, temperature, pH, and inoculation rate to find the optimal conditions. Khakhariya et al. [126] explored this approach by studying the production of health-promoting BAPs in fermented buffalo and camel milk by Limosilactobacillus fermentum (KGL4) and Saccharomyces cerevisiae (WBS2A). They monitored the variation in ACE-inhibitory, antidiabetic, and proteolytic activity at 37 °C and at multiple time intervals (12, 24, 36, and 48 h) and inoculation rates (1.5%, 2.0%, and 2.5%), finding the optimal fermentation conditions to be a 2.5% inoculation rate and 48 h. One investigation on BAPs in flaxseed milk fermented with L. plantarum (NCDC 374) revealed that the optimal conditions to guarantee the best bioactivity (antioxidant, ACE-inhibition, and proteolysis) were a 4.20% inoculum size and 126 h of fermentation time [127]. Additionally, it was shown that pH is critical to optimizing BAP retrieval and bioactivity in fermented foods. For instance, the functional properties and BAP production in lentils fermented using L. plantarum combined with a commercial protease (Savinase® 16 L) benefited from a mild alkaline environment. A multivariate analysis highlighted a pH of 8.5 and 11.6 h of incubation time as the optimum [128]. Taken together, these studies highlight the possibility of improving the fermentation performance of foods, maximizing BAP release.

6.2. Strategies to Improve the Stability and Bioavailability of BAPs

Improving the stability and bioavailability of BAPs is essential for maximizing their health benefits in functional foods, nutraceuticals, and pharmaceuticals. Despite their promising biological activities, BAPs face several challenges that limit their application, particularly their susceptibility to enzymatic degradation, low bioavailability, and poor stability under various physiological and processing conditions [129]. Several advanced strategies have been developed to address these limitations, including encapsulation technologies, carrier matrices, and physicochemical modifications [10,130].
One major challenge in enhancing BAPs’ stability and bioavailability is their susceptibility to gastrointestinal degradation. Peptidases in the stomach and intestinal lumen degrade BAPs, reducing their ability to reach the bloodstream in their active form [131]. Encapsulation is a commonly employed technique for maintaining bioactive compounds’ functional and physicochemical properties. It involves surrounding solid or liquid particles with a coating or embedding them in a matrix [132].
Several materials can be used as carriers for peptide encapsulation, including proteins, polysaccharides, and lipids. Each type of carrier offers distinct advantages and faces specific challenges. Proteins, for instance, possess valuable functional properties, such as emulsification, water retention, and the ability to form gels, making them suitable candidates for encapsulation [133,134,135].
Polysaccharides are another promising class of carrier materials for encapsulation due to their structural stability, abundance, and low cost [136]. They have reactive functional groups that can form interactions with BAPs, helping to stabilize and protect them during processing and storage [132]. Polysaccharides such as starch, dextrin, gum arabic, pectin, and chitosan have been widely used in peptide encapsulation [132,137]. Their use is often combined with proteins to achieve better encapsulation efficiency and bioactive compound stabilization [131,138].
Lipid-based carriers, such as liposomes and nanoliposomes, have also gained significant attention as good systems for BAPs’ encapsulation [132]. Liposomes consist of phospholipid bilayers, which can be useful to encapsulate both hydrophilic and lipophilic substances [131,139]. This versatility makes liposomes an attractive alternative for delivering a wide range of bioactive compounds. Nanoliposomes, which are smaller in size, provide even better protection and improved bioavailability by facilitating the controlled release of encapsulated peptides [140,141]. For instance, BAPs derived from shrimp waste have been stabilized through chitosan-coated nanoliposome formation [142].
Among the methods for peptide encapsulation, spray drying is a popular method for encapsulating bioactive compounds, including peptides, because it is economical, flexible, and capable of producing stable powders that can be easily incorporated into food products. During the spray drying process, peptides are mixed with carrier materials that form a protective film around the peptide [132]. This approach prevents peptide degradation during processing and storage but also effectively masks undesirable flavors, such as bitterness, as demonstrated by Sarabandi et al. [134] through spray drying encapsulation to stabilize peptides from oleaster seeds.
Another method is nanoencapsulation, which represents a promising approach for improving peptide stability and bioavailability. Nanoparticles can be engineered to protect peptides from degradation, enhance their absorption in the intestine, and ensure their targeted delivery to specific tissues [143]. Nanoparticles made from materials such as dextran, chitosan, or amphiphilic molecules can improve the bioaccessibility and controlled release of peptides. These nanoscale systems offer several advantages over traditional encapsulation methods, including increased surface area, enhanced cellular uptake, and the ability to penetrate physiological barriers [144].
Physicochemical modifications of peptides such as the Maillard reaction (MR) also hold the potential for improving their stability and bioavailability. The MR involves the interaction between amino acids and reducing sugars, which leads to the formation of peptide–sugar conjugates [145]. These conjugates have been shown to enhance the stability of peptides during processing and storage and improve their taste and overall sensory properties. Additionally, MR-conjugated peptides may exhibit enhanced biological activities, such as antioxidant or antimicrobial effects, further increasing their potential as functional ingredients in foods and nutraceuticals [130].
Therefore, improving the stability and bioavailability of BAPs is crucial for their successful incorporation into functional foods, nutraceuticals, and pharmaceuticals. Encapsulation and physicochemical modifications are among the most promising strategies for achieving these goals.

7. Conclusions and Future Perspectives

By reviewing a substantial slice of the literature, we have confirmed microbial fermentation as a valuable natural technology extensively used to enrich several animal- and plant-derived foods with BAPs. This approach offers structurally variable peptides due to the diversity of microbial proteases but also supports a wide range of beneficial biological activities, namely antimicrobial, anti-inflammatory, antioxidant, and antihypertensive. Adopting innovative technologies such as ultrasound, microwave, and high pressure, combined with optimizing fermentation parameters, represents a promising avenue for scaling up this process. Additionally, finding appropriate delivery strategies is crucial for guaranteeing the stability and efficacy of BAPs. As research and fermentation technologies continue to advance, new perspectives are emerging for developing functional products with high added value. This will also be achieved by establishing interdisciplinary collaborations, involving food technologists, microbiologists, biochemists, and medical professionals, ensuring the scalability of BAPs’ production processes.

Author Contributions

Conceptualization, L.P.F. and M.G.; writing—original draft preparation, L.P.F., A.C., and F.V.; writing—review and editing, L.P.F., A.C., F.V., and M.G.; visualization, L.P.F. and M.G.; supervision, M.G. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Marco, M.L.; Sanders, M.E.; Gänzle, M.; Arrieta, M.C.; Cotter, P.D.; De Vuyst, L.; Hill, C.; Holzapfel, W.; Lebeer, S.; Merenstein, D.; et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) Consensus Statement on Fermented Foods. Nat. Rev. Gastroenterol. Hepatol. 2021, 18, 196–208. [Google Scholar] [CrossRef] [PubMed]
  2. García-Burgos, M.; Moreno-Fernández, J.; Alférez, M.J.M.; Díaz-Castro, J.; López-Aliaga, I. New Perspectives in Fermented Dairy Products and Their Health Relevance. J. Funct. Foods 2020, 72, 104059. [Google Scholar] [CrossRef]
  3. Diez-Ozaeta, I.; Astiazaran, O.J. Fermented Foods: An Update on Evidence-Based Health Benefits and Future Perspectives. Food Res. Int. 2022, 156, 111133. [Google Scholar] [CrossRef]
  4. Korhonen, H.; Pihlanto, A. Bioactive Peptides: Production and Functionality. Int. Dairy. J. 2006, 16, 945–960. [Google Scholar] [CrossRef]
  5. Chalamaiah, M.; Keskin Ulug, S.; Hong, H.; Wu, J. Regulatory Requirements of Bioactive Peptides (Protein Hydrolysates) from Food Proteins. J. Funct. Foods 2019, 58, 123–129. [Google Scholar] [CrossRef]
  6. Mirzaei, M.; Shavandi, A.; Mirdamadi, S.; Soleymanzadeh, N.; Motahari, P.; Mirdamadi, N.; Moser, M.; Subra, G.; Alimoradi, H.; Goriely, S. Bioactive Peptides from Yeast: A Comparative Review on Production Methods, Bioactivity, Structure-Function Relationship, and Stability. Trends Food Sci. Technol. 2021, 118, 297–315. [Google Scholar] [CrossRef]
  7. Manzoor, M.; Singh, J.; Gani, A. Exploration of Bioactive Peptides from Various Origin as Promising Nutraceutical Treasures: In Vitro, in Silico and in Vivo Studies. Food Chem. 2022, 373, 131395. [Google Scholar] [CrossRef]
  8. Martinez-Villaluenga, C.; Peñas, E.; Frias, J. Bioactive Peptides in Fermented Foods. In Fermented Foods in Health and Disease Prevention; Elsevier: Amsterdam, The Netherlands, 2017; pp. 23–47. [Google Scholar]
  9. Tadesse, S.A.; Emire, S.A. Production and Processing of Antioxidant Bioactive Peptides: A Driving Force for the Functional Food Market. Heliyon 2020, 6, e04765. [Google Scholar] [CrossRef]
  10. Jiang, Y.; Sun, J.; Chandrapala, J.; Majzoobi, M.; Brennan, C.; Zeng, X.; Sun, B. Recent Progress of Food-derived Bioactive Peptides: Extraction, Purification, Function, and Encapsulation. Food Front. 2024, 5, 1240–1264. [Google Scholar] [CrossRef]
  11. Mannaa, M.; Han, G.; Seo, Y.-S.; Park, I. Evolution of Food Fermentation Processes and the Use of Multi-Omics in Deciphering the Roles of the Microbiota. Foods 2021, 10, 2861. [Google Scholar] [CrossRef]
  12. Wang, Z.; Wang, L. Impact of Sourdough Fermentation on Nutrient Transformations in Cereal-Based Foods: Mechanisms, Practical Applications, and Health Implications. Grain Oil Sci. Technol. 2024, 7, 124–132. [Google Scholar] [CrossRef]
  13. Day, C.N.; Morawicki, R.O. Effects of Fermentation by Yeast and Amylolytic Lactic Acid Bacteria on Grain Sorghum Protein Content and Digestibility. J. Food Qual. 2018, 2018, 1–8. [Google Scholar] [CrossRef]
  14. Nkhata, S.G.; Ayua, E.; Kamau, E.H.; Shingiro, J. Fermentation and Germination Improve Nutritional Value of Cereals and Legumes through Activation of Endogenous Enzymes. Food Sci. Nutr. 2018, 6, 2446–2458. [Google Scholar] [CrossRef] [PubMed]
  15. Ulug, S.K.; Jahandideh, F.; Wu, J. Novel Technologies for the Production of Bioactive Peptides. Trends Food Sci. Technol. 2021, 108, 27–39. [Google Scholar] [CrossRef]
  16. Hernández-Ledesma, B.; del Mar Contreras, M.; Recio, I. Antihypertensive Peptides: Production, Bioavailability and Incorporation into Foods. Adv. Colloid. Interface Sci. 2011, 165, 23–35. [Google Scholar] [CrossRef]
  17. Kumari, R.; Sharma, N.; Sharma, S.; Samurailatpam, S.; Padhi, S.; Singh, S.P.; Kumar Rai, A. Production and Characterization of Bioactive Peptides in Fermented Soybean Meal Produced Using Proteolytic Bacillus Species Isolated from Kinema. Food Chem. 2023, 421, 136130. [Google Scholar] [CrossRef]
  18. Chen, Y.; Gao, X.; Wei, Y.; Liu, Q.; Jiang, Y.; Zhao, L.; Ulaah, S. Isolation, Purification and the Anti-Hypertensive Effect of a Novel Angiotensin I-Converting Enzyme (ACE) Inhibitory Peptide from Ruditapes philippinarum Fermented with Bacillus natto. Food Funct. 2018, 9, 5230–5237. [Google Scholar] [CrossRef]
  19. Ahmed, T.; Juhász, A.; Bose, U.; Shiferaw Terefe, N.; Colgrave, M.L. Research Trends in Production, Separation, and Identification of Bioactive Peptides from Fungi—A Critical Review. J. Funct. Foods 2024, 119, 106343. [Google Scholar] [CrossRef]
  20. Ji, D.; Ma, J.; Xu, M.; Agyei, D. Cell-envelope Proteinases from Lactic Acid Bacteria: Biochemical Features and Biotechnological Applications. Compr. Rev. Food Sci. Food Saf. 2021, 20, 369–400. [Google Scholar] [CrossRef]
  21. Raveschot, C.; Cudennec, B.; Coutte, F.; Flahaut, C.; Fremont, M.; Drider, D.; Dhulster, P. Production of Bioactive Peptides by Lactobacillus Species: From Gene to Application. Front. Microbiol. 2018, 9, 2354. [Google Scholar] [CrossRef]
  22. Sadat-Mekmene, L.; Jardin, J.; Corre, C.; Mollé, D.; Richoux, R.; Delage, M.-M.; Lortal, S.; Gagnaire, V. Simultaneous Presence of PrtH and PrtH2 Proteinases in Lactobacillus helveticus Strains Improves Breakdown of the Pure αs1-Casein. Appl. Environ. Microbiol. 2011, 77, 179–186. [Google Scholar] [CrossRef] [PubMed]
  23. Miyamoto, M.; Ueno, H.M.; Watanabe, M.; Tatsuma, Y.; Seto, Y.; Miyamoto, T.; Nakajima, H. Distinctive Proteolytic Activity of Cell Envelope Proteinase of Lactobacillus helveticus Isolated from Airag, a Traditional Mongolian Fermented Mare’s Milk. Int. J. Food Microbiol. 2015, 197, 65–71. [Google Scholar] [CrossRef] [PubMed]
  24. Cruz-Casas, D.E.; Aguilar, C.N.; Ascacio-Valdés, J.A.; Rodríguez-Herrera, R.; Chávez-González, M.L.; Flores-Gallegos, A.C. Enzymatic Hydrolysis and Microbial Fermentation: The Most Favorable Biotechnological Methods for the Release of Bioactive Peptides. Food Chem. Mol. Sci. 2021, 3, 100047. [Google Scholar] [CrossRef] [PubMed]
  25. Melini, F.; Melini, V.; Luziatelli, F.; Ficca, A.G.; Ruzzi, M. Health-Promoting Components in Fermented Foods: An Up-to-Date Systematic Review. Nutrients 2019, 11, 1189. [Google Scholar] [CrossRef]
  26. Dharmisthaben, P.; Basaiawmoit, B.; Sakure, A.; Das, S.; Maurya, R.; Bishnoi, M.; Kondepudi, K.K.; Hati, S. Exploring Potentials of Antioxidative, Anti-Inflammatory Activities and Production of Bioactive Peptides in Lactic Fermented Camel Milk. Food Biosci. 2021, 44, 101404. [Google Scholar] [CrossRef]
  27. Li, H.; Wu, J.; Wan, J.; Zhou, Y.; Zhu, Q. Extraction and Identification of Bioactive Peptides from Panxian Dry-Cured Ham with Multifunctional Activities. LWT 2022, 160, 113326. [Google Scholar] [CrossRef]
  28. Folliero, V.; Lama, S.; Franci, G.; Giugliano, R.; D’Auria, G.; Ferranti, P.; Pourjula, M.; Galdiero, M.; Stiuso, P. Casein-Derived Peptides from the Dairy Product Kashk Exhibit Wound Healing Properties and Antibacterial Activity against Staphylococcus aureus: Structural and Functional Characterization. Food Res. Int. 2022, 153, 110949. [Google Scholar] [CrossRef]
  29. Taniguchi, M.; Aida, R.; Saito, K.; Ochiai, A.; Takesono, S.; Saitoh, E.; Tanaka, T. Identification and Characterization of Multifunctional Cationic Peptides from Traditional Japanese Fermented Soybean Natto Extracts. J. Biosci. Bioeng. 2019, 127, 472–478. [Google Scholar] [CrossRef]
  30. Gallego, M.; Mora, L.; Toldrá, F. Characterisation of the Antioxidant Peptide AEEEYPDL and Its Quantification in Spanish Dry-Cured Ham. Food Chem. 2018, 258, 8–15. [Google Scholar] [CrossRef]
  31. Gibbs, B.F.; Zougman, A.; Masse, R.; Mulligan, C. Production and Characterization of Bioactive Peptides from Soy Hydrolysate and Soy-Fermented Food. Food Res. Int. 2004, 37, 123–131. [Google Scholar] [CrossRef]
  32. Nasri, R.; Abdelhedi, O.; Nasri, M.; Jridi, M. Fermented Protein Hydrolysates: Biological Activities and Applications. Curr. Opin. Food Sci. 2022, 43, 120–127. [Google Scholar] [CrossRef]
  33. Sánchez, A.; Vázquez, A. Bioactive Peptides: A Review. Food Qual. Saf. 2017, 1, 29–46. [Google Scholar] [CrossRef]
  34. Tsermoula, P.; Khakimov, B.; Nielsen, J.H.; Engelsen, S.B. WHEY—The Waste-Stream That Became More Valuable than the Food Product. Trends Food Sci. Technol. 2021, 118, 230–241. [Google Scholar] [CrossRef]
  35. Mann, B.; Athira, S.; Sharma, R.; Bajaj, R. Bioactive Peptides in Yogurt. In Yogurt in Health and Disease Prevention; Elsevier: Amsterdam, The Netherlands, 2017; pp. 411–426. [Google Scholar]
  36. Chourasia, R.; Abedin, M.M.; Chiring Phukon, L.; Sahoo, D.; Singh, S.P.; Rai, A.K. Biotechnological Approaches for the Production of Designer Cheese with Improved Functionality. Compr. Rev. Food Sci. Food Saf. 2021, 20, 960–979. [Google Scholar] [CrossRef]
  37. Maïworé, J.; Tatsadjieu Ngoune, L.; Piro-Metayer, I.; Montet, D. Identification of Yeasts Present in Artisanal Yoghurt and Traditionally Fermented Milks Consumed in the Northern Part of Cameroon. Sci. Afr. 2019, 6, e00159. [Google Scholar] [CrossRef]
  38. Dullius, A.; Rama, G.R.; Giroldi, M.; Goettert, M.I.; Lehn, D.N.; Volken de Souza, C.F. Bioactive Peptide Production in Fermented Foods. In Current Developments in Biotechnology and Bioengineering; Elsevier: Amsterdam, The Netherlands, 2022; pp. 47–72. [Google Scholar]
  39. Padhi, S.; Sharma, S.; Sahoo, D.; Montet, D.; Rai, A.K. Potential of Lactic Acid Bacteria as Starter Cultures for Food Fermentation and as Producers of Biochemicals for Value Addition. In Lactic Acid Bacteria in Food Biotechnology; Elsevier: Amsterdam, The Netherlands, 2022; pp. 281–304. [Google Scholar]
  40. Martini, S.; Conte, A.; Tagliazucchi, D. Effect of Ripening and in Vitro Digestion on the Evolution and Fate of Bioactive Peptides in Parmigiano-Reggiano Cheese. Int. Dairy. J. 2020, 105, 104668. [Google Scholar] [CrossRef]
  41. Amorim, F.G.; Coitinho, L.B.; Dias, A.T.; Friques, A.G.F.; Monteiro, B.L.; de Rezende, L.C.D.; Pereira, T.d.M.C.; Campagnaro, B.P.; De Pauw, E.; Vasquez, E.C.; et al. Identification of New Bioactive Peptides from Kefir Milk through Proteopeptidomics: Bioprospection of Antihypertensive Molecules. Food Chem. 2019, 282, 109–119. [Google Scholar] [CrossRef]
  42. Chen, Y.F.; Zhao, W.J.; Wu, R.N.; Sun, Z.H.; Zhang, W.Y.; Wang, J.C.; Bilige, M.; Zhang, H.P. Proteome Analysis of Lactobacillus helveticus H9 during Growth in Skim Milk. J. Dairy. Sci. 2014, 97, 7413–7425. [Google Scholar] [CrossRef]
  43. Chen, Y.; Li, C.; Xue, J.; Kwok, L.; Yang, J.; Zhang, H.; Menghe, B. Characterization of Angiotensin-Converting Enzyme Inhibitory Activity of Fermented Milk Produced by Lactobacillus helveticus. J. Dairy. Sci. 2015, 98, 5113–5124. [Google Scholar] [CrossRef]
  44. Baptista, D.P.; Galli, B.D.; Cavalheiro, F.G.; Negrão, F.; Eberlin, M.N.; Gigante, M.L. Lactobacillus helveticus LH-B02 Favours the Release of Bioactive Peptide during Prato Cheese Ripening. Int. Dairy. J. 2018, 87, 75–83. [Google Scholar] [CrossRef]
  45. Bielecka, M.; Cichosz, G.; Czeczot, H. Antioxidant, Antimicrobial and Anticarcinogenic Activities of Bovine Milk Proteins and Their Hydrolysates—A Review. Int. Dairy. J. 2022, 127, 105208. [Google Scholar] [CrossRef]
  46. Zenezini Chiozzi, R.; Capriotti, A.L.; Cavaliere, C.; La Barbera, G.; Piovesana, S.; Samperi, R.; Laganà, A. Purification and Identification of Endogenous Antioxidant and ACE-Inhibitory Peptides from Donkey Milk by Multidimensional Liquid Chromatography and NanoHPLC-High Resolution Mass Spectrometry. Anal. Bioanal. Chem. 2016, 408, 5657–5666. [Google Scholar] [CrossRef] [PubMed]
  47. El-Salam, M.H.A.; El-Shibiny, S. Bioactive Peptides of Buffalo, Camel, Goat, Sheep, Mare, and Yak Milks and Milk Products. Food Rev. Int. 2013, 29, 1–23. [Google Scholar] [CrossRef]
  48. Mora, L.; Escudero, E.; Aristoy, M.-C.; Toldrá, F. A Peptidomic Approach to Study the Contribution of Added Casein Proteins to the Peptide Profile in Spanish Dry-Fermented Sausages. Int. J. Food Microbiol. 2015, 212, 41–48. [Google Scholar] [CrossRef]
  49. Mejri, L.; Vásquez-Villanueva, R.; Hassouna, M.; Marina, M.L.; García, M.C. Identification of Peptides with Antioxidant and Antihypertensive Capacities by RP-HPLC-Q-TOF-MS in Dry Fermented Camel Sausages Inoculated with Different Starter Cultures and Ripening Times. Food Res. Int. 2017, 100, 708–716. [Google Scholar] [CrossRef]
  50. Takeda, S.; Matsufuji, H.; Nakade, K.; Takenoyama, S.; Ahhmed, A.; Sakata, R.; Kawahara, S.; Muguruma, M. Investigation of Lactic Acid Bacterial Strains for Meat Fermentation and the Product’s Antioxidant and Angiotensin-I-converting-enzyme Inhibitory Activities. Anim. Sci. J. 2017, 88, 507–516. [Google Scholar] [CrossRef]
  51. Kononiuk, A.D.; Karwowska, M. Bioactive Compounds in Fermented Sausages Prepared from Beef and Fallow Deer Meat with Acid Whey Addition. Molecules 2020, 25, 2429. [Google Scholar] [CrossRef]
  52. Chai, K.F.; Voo, A.Y.H.; Chen, W.N. Bioactive Peptides from Food Fermentation: A Comprehensive Review of Their Sources, Bioactivities, Applications, and Future Development. Compr. Rev. Food Sci. Food Saf. 2020, 19, 3825–3885. [Google Scholar] [CrossRef]
  53. Gabriele, M.; Pucci, L. Fermentation and Germination as a Way to Improve Cereals Antioxidant and Antiinflammatory Properties. In Current Advances for Development of Functional Foods Modulating Inflammation and Oxidative Stress; Elsevier: Amsterdam, The Netherlands, 2022; pp. 477–497. [Google Scholar]
  54. Corpuz, H.M.; Fujii, H.; Nakamura, S.; Katayama, S. Fermented Rice Peptides Attenuate Scopolamine-Induced Memory Impairment in Mice by Regulating Neurotrophic Signaling Pathways in the Hippocampus. Brain Res. 2019, 1720, 146322. [Google Scholar] [CrossRef]
  55. Wu, H.; Rui, X.; Li, W.; Xiao, Y.; Zhou, J.; Dong, M. Whole-Grain Oats (Avena sativa L.) as a Carrier of Lactic Acid Bacteria and a Supplement Rich in Angiotensin I-Converting Enzyme Inhibitory Peptides through Solid-State Fermentation. Food Funct. 2018, 9, 2270–2281. [Google Scholar] [CrossRef]
  56. Ayyash, M.; Johnson, S.K.; Liu, S.-Q.; Mesmari, N.; Dahmani, S.; Al Dhaheri, A.S.; Kizhakkayil, J. In Vitro Investigation of Bioactivities of Solid-State Fermented Lupin, Quinoa and Wheat Using Lactobacillus spp. Food Chem. 2019, 275, 50–58. [Google Scholar] [CrossRef] [PubMed]
  57. Rizzello, C.G.; Nionelli, L.; Coda, R.; Gobbetti, M. Synthesis of the Cancer Preventive Peptide Lunasin by Lactic Acid Bacteria During Sourdough Fermentation. Nutr. Cancer 2012, 64, 111–120. [Google Scholar] [CrossRef] [PubMed]
  58. Chi, C.-H.; Cho, S.-J. Improvement of Bioactivity of Soybean Meal by Solid-State Fermentation with Bacillus amyloliquefaciens versus Lactobacillus Spp. and Saccharomyces cerevisiae. LWT—Food Sci. Technol. 2016, 68, 619–625. [Google Scholar] [CrossRef]
  59. Xiao, Y.; Sun, M.; Zhang, Q.; Chen, Y.; Miao, J.; Rui, X.; Dong, M. Effects of Cordyceps militaris (L.) Fr. Fermentation on the Nutritional, Physicochemical, Functional Properties and Angiotensin I Converting Enzyme Inhibitory Activity of Red Bean (Phaseolus angularis [Willd.] W.F. Wight.) Flour. J. Food Sci. Technol. 2018, 55, 1244–1255. [Google Scholar] [CrossRef]
  60. Ihn, H.J.; Kim, J.A.; Lim, S.; Nam, S.-H.; Hwang, S.H.; Lim, J.; Kim, G.-Y.; Choi, Y.H.; Jeon, Y.-J.; Lee, B.-J.; et al. Fermented Oyster Extract Prevents Ovariectomy-Induced Bone Loss and Suppresses Osteoclastogenesis. Nutrients 2019, 11, 1392. [Google Scholar] [CrossRef]
  61. Kim, J.A.; Yao, Z.; Kim, H.-J.; Kim, J.H. Properties of Gul Jeotgal (Oyster Jeotgal) Prepared with Different Types of Salt and Bacillus subtilis JS2 as Starter. Microbiol. Biotechnol. Lett. 2018, 46, 1–8. [Google Scholar] [CrossRef]
  62. Jemil, I.; Abdelhedi, O.; Mora, L.; Nasri, R.; Aristoy, M.-C.; Jridi, M.; Hajji, M.; Toldrá, F.; Nasri, M. Peptidomic Analysis of Bioactive Peptides in Zebra Blenny (Salaria basilisca) Muscle Protein Hydrolysate Exhibiting Antimicrobial Activity Obtained by Fermentation with Bacillus Mojavensis A21. Process Biochem. 2016, 51, 2186–2197. [Google Scholar] [CrossRef]
  63. Najafian, L.; Babji, A.S. Purification and Identification of Antioxidant Peptides from Fermented Fish Sauce (Budu). J. Aquat. Food Product. Technol. 2019, 28, 14–24. [Google Scholar] [CrossRef]
  64. Najafian, L.; Babji, A.S. Fractionation and Identification of Novel Antioxidant Peptides from Fermented Fish (Pekasam). J. Food Meas. Charact. 2018, 12, 2174–2183. [Google Scholar] [CrossRef]
  65. Kleekayai, T.; Harnedy, P.A.; O’Keeffe, M.B.; Poyarkov, A.A.; CunhaNeves, A.; Suntornsuk, W.; FitzGerald, R.J. Extraction of Antioxidant and ACE Inhibitory Peptides from Thai Traditional Fermented Shrimp Pastes. Food Chem. 2015, 176, 441–447. [Google Scholar] [CrossRef]
  66. Duarte-Mata, D.I.; Salinas-Carmona, M.C. Antimicrobial Peptides’ Immune Modulation Role in Intracellular Bacterial Infection. Front. Immunol. 2023, 14, 1119574. [Google Scholar] [CrossRef] [PubMed]
  67. Zhang, Q.-Y.; Yan, Z.-B.; Meng, Y.-M.; Hong, X.-Y.; Shao, G.; Ma, J.-J.; Cheng, X.-R.; Liu, J.; Kang, J.; Fu, C.-Y. Antimicrobial Peptides: Mechanism of Action, Activity and Clinical Potential. Mil. Med. Res. 2021, 8, 48. [Google Scholar] [CrossRef] [PubMed]
  68. Powers, J.-P.S.; Hancock, R.E.W. The Relationship between Peptide Structure and Antibacterial Activity. Peptides 2003, 24, 1681–1691. [Google Scholar] [CrossRef]
  69. Ciulla, M.G.; Gelain, F. Structure–Activity Relationships of Antibacterial Peptides. Microb. Biotechnol. 2023, 16, 757–777. [Google Scholar] [CrossRef]
  70. Echegaray, N.; Yilmaz, B.; Sharma, H.; Kumar, M.; Pateiro, M.; Ozogul, F.; Lorenzo, J.M. A Novel Approach to Lactiplantibacillus plantarum: From Probiotic Properties to the Omics Insights. Microbiol. Res. 2023, 268, 127289. [Google Scholar] [CrossRef]
  71. Yilmaz, B.; Bangar, S.P.; Echegaray, N.; Suri, S.; Tomasevic, I.; Manuel Lorenzo, J.; Melekoglu, E.; Rocha, J.M.; Ozogul, F. The Impacts of Lactiplantibacillus plantarum on the Functional Properties of Fermented Foods: A Review of Current Knowledge. Microorganisms 2022, 10, 826. [Google Scholar] [CrossRef]
  72. Algboory, H.L.; Muhialdin, B.J. Novel Peptides Contribute to the Antimicrobial Activity of Camel Milk Fermented with Lactobacillus plantarum IS10. Food Control 2021, 126, 108057. [Google Scholar] [CrossRef]
  73. Yu, S.; Qian, Y.; Gao, Q.; Yan, Y.; Huang, Y.; Wu, Z.; Luo, X.; Shen, J.; Liu, Y. Discovery, Characterization, and Application of a Novel Antimicrobial Peptide Produced by Lactiplantibacillus plantarum FB-2. Food Biosci. 2024, 58, 103663. [Google Scholar] [CrossRef]
  74. Arulrajah, B.; Qoms, M.S.; Muhialdin, B.J.; Hasan, H.; Zarei, M.; Meor Hussin, A.S.; Chau, D.-M.; Saari, N. Antibacterial and Antifungal Activity of Kenaf Seed Peptides and Their Effect on Microbiological Safety and Physicochemical Properties of Some Food Models. Food Control 2022, 140, 109119. [Google Scholar] [CrossRef]
  75. Liu, H.; Zhang, L.; Yu, J.; Shao, S. Advances in the Application and Mechanism of Bioactive Peptides in the Treatment of Inflammation. Front. Immunol. 2024, 15, 1413179. [Google Scholar] [CrossRef]
  76. Li, E.C.; Heran, B.S.; Wright, J.M. Angiotensin Converting Enzyme (ACE) Inhibitors versus Angiotensin Receptor Blockers for Primary Hypertension. In Cochrane Database of Systematic Reviews; Li, E.C., Ed.; John Wiley & Sons, Ltd.: Chichester, UK, 2011. [Google Scholar]
  77. Balti, R.; Bougatef, A.; Sila, A.; Guillochon, D.; Dhulster, P.; Nedjar-Arroume, N. Nine Novel Angiotensin I-Converting Enzyme (ACE) Inhibitory Peptides from Cuttlefish (Sepia officinalis) Muscle Protein Hydrolysates and Antihypertensive Effect of the Potent Active Peptide in Spontaneously Hypertensive Rats. Food Chem. 2015, 170, 519–525. [Google Scholar] [CrossRef] [PubMed]
  78. Majumder, K.; Chakrabarti, S.; Morton, J.S.; Panahi, S.; Kaufman, S.; Davidge, S.T.; Wu, J. Egg-Derived ACE-Inhibitory Peptides IQW and LKP Reduce Blood Pressure in Spontaneously Hypertensive Rats. J. Funct. Foods 2015, 13, 50–60. [Google Scholar] [CrossRef]
  79. Daskaya-Dikmen, C.; Yucetepe, A.; Karbancioglu-Guler, F.; Daskaya, H.; Ozcelik, B. Angiotensin-I-Converting Enzyme (ACE)-Inhibitory Peptides from Plants. Nutrients 2017, 9, 316. [Google Scholar] [CrossRef] [PubMed]
  80. Chen, L.; Zhang, Q.; Ji, Z.; Shu, G.; Chen, H. Production and Fermentation Characteristics of Angiotensin-I-Converting Enzyme Inhibitory Peptides of Goat Milk Fermented by a Novel Wild Lactobacillus plantarum 69. LWT 2018, 91, 532–540. [Google Scholar] [CrossRef]
  81. Wu, N.; Xu, W.; Liu, K.; Xia, Y. Shuangquan Angiotensin-Converting Enzyme Inhibitory Peptides from Lactobacillus delbrueckii QS306 Fermented Milk. J. Dairy. Sci. 2019, 102, 5913–5921. [Google Scholar] [CrossRef]
  82. Gallego, M.; Mora, L.; Escudero, E.; Toldrá, F. Bioactive Peptides and Free Amino Acids Profiles in Different Types of European Dry-Fermented Sausages. Int. J. Food Microbiol. 2018, 276, 71–78. [Google Scholar] [CrossRef]
  83. Jakubczyk, A.; Karaś, M.; Złotek, U.; Szymanowska, U.; Baraniak, B.; Bochnak, J. Peptides Obtained from Fermented Faba Bean Seeds (Vicia faba) as Potential Inhibitors of an Enzyme Involved in the Pathogenesis of Metabolic Syndrome. LWT 2019, 105, 306–313. [Google Scholar] [CrossRef]
  84. Wu, J.; Aluko, R.E.; Nakai, S. Structural Requirements of Angiotensin I-Converting Enzyme Inhibitory Peptides: Quantitative Structure-Activity Relationship Modeling of Peptides Containing 4-10 Amino Acid Residues. QSAR Comb. Sci. 2006, 25, 873–880. [Google Scholar] [CrossRef]
  85. Wu, J.; Aluko, R.E.; Nakai, S. Structural Requirements of Angiotensin I-Converting Enzyme Inhibitory Peptides: Quantitative Structure−Activity Relationship Study of Di- and Tripeptides. J. Agric. Food Chem. 2006, 54, 732–738. [Google Scholar] [CrossRef]
  86. Bhuyan, B.J.; Mugesh, G. Antioxidant Activity of Peptide-Based Angiotensin Converting Enzyme Inhibitors. Org. Biomol. Chem. 2012, 10, 2237. [Google Scholar] [CrossRef]
  87. Roberts, P.R.; Burney, J.D.; Black, K.W.; Zaloga, G.P. Effect of Chain Length on Absorption of Biologically Active Peptides from the Gastrointestinal Tract. Digestion 1999, 60, 332–337. [Google Scholar] [CrossRef] [PubMed]
  88. Shen, W.; Matsui, T. Intestinal Absorption of Small Peptides: A Review. Int. J. Food Sci. Technol. 2019, 54, 1942–1948. [Google Scholar] [CrossRef]
  89. Mirdhayati, I.; Zain, W.N.H.; Fatah, A.; Yokoyama, I.; Arihara, K. Purification of Angiotensin Converting Enzyme Inhibitory Peptides and Antihypertensive Effect Generated from Indonesian Traditional Fermented Beef (Cangkuk). Anim. Biosci. 2024, 37, 1799–1808. [Google Scholar] [CrossRef] [PubMed]
  90. Miyazaki, H.; Nakamura, T.; Ohki, K.; Nagai, K. Effects of the Bioactive Peptides Ile-Pro-Pro and Val-Pro-Pro upon Autonomic Neurotransmission and Blood Pressure in Spontaneously Hypertensive Rats. Auton. Neurosci. 2017, 208, 88–92. [Google Scholar] [CrossRef]
  91. Cicero, A.F.G.; Colletti, A.; Rosticci, M.; Cagnati, M.; Urso, R.; Giovannini, M.; Borghi, C.; D’Addato, S. Effect of Lactotripeptides (Isoleucine–Proline–Proline/Valine–Proline–Proline) on Blood Pressure and Arterial Stiffness Changes in Subjects with Suboptimal Blood Pressure Control and Metabolic Syndrome: A Double-Blind, Randomized, Crossover Clinical Trial. Metab. Syndr. Relat. Disord. 2016, 14, 161–166. [Google Scholar] [CrossRef]
  92. Moayedi, A.; Mora, L.; Aristoy, M.C.; Safari, M.; Hashemi, M.; Toldrá, F. Peptidomic Analysis of Antioxidant and ACE-Inhibitory Peptides Obtained from Tomato Waste Proteins Fermented Using Bacillus subtilis. Food Chem. 2018, 250, 180–187. [Google Scholar] [CrossRef]
  93. Theansungnoen, T.; Yaraksa, N.; Daduang, S.; Dhiravisit, A.; Thammasirirak, S. Purification and Characterization of Antioxidant Peptides from Leukocyte Extract of Crocodylus siamensis. Protein J. 2014, 33, 24–31. [Google Scholar] [CrossRef]
  94. Puchalska, P.; Marina, M.L.; García, M.C. Isolation and Identification of Antioxidant Peptides from Commercial Soybean-Based Infant Formulas. Food Chem. 2014, 148, 147–154. [Google Scholar] [CrossRef]
  95. Gaspar-Pintiliescu, A.; Oancea, A.; Cotarlet, M.; Vasile, A.M.; Bahrim, G.E.; Shaposhnikov, S.; Craciunescu, O.; Oprita, E.I. Angiotensin-converting Enzyme Inhibition, Antioxidant Activity and Cytotoxicity of Bioactive Peptides from Fermented Bovine Colostrum. Int. J. Dairy. Technol. 2020, 73, 108–116. [Google Scholar] [CrossRef]
  96. Zou, T.-B.; He, T.-P.; Li, H.-B.; Tang, H.-W.; Xia, E.-Q. The Structure-Activity Relationship of the Antioxidant Peptides from Natural Proteins. Molecules 2016, 21, 72. [Google Scholar] [CrossRef]
  97. Yang, W. Evaluation of the Antioxidant Activity and Identification of Potential Antioxidant Peptides in Commercially Available Probiotic Cheddar Cheese. LWT 2024, 205, 116486. [Google Scholar] [CrossRef]
  98. Devi, S.; Kumar, N.; Kapila, S.; Mada, S.B.; Reddi, S.; Vij, R.; Kapila, R. Buffalo Casein Derived Peptide Can Alleviates H2O2 Induced Cellular Damage and Necrosis in Fibroblast Cells. Exp. Toxicol. Pathol. 2017, 69, 485–495. [Google Scholar] [CrossRef] [PubMed]
  99. Wan, M.-Y.; Dong, G.; Yang, B.-Q.; Feng, H. Identification and Characterization of a Novel Antioxidant Peptide from Feather Keratin Hydrolysate. Biotechnol. Lett. 2016, 38, 643–649. [Google Scholar] [CrossRef]
  100. Lin, H.; Zhao, J.; Xie, Y.; Tang, J.; Wang, Q.; Zhao, J.; Xu, M.; Liu, P. Identification and Molecular Mechanisms of Novel Antioxidant Peptides from Fermented Broad Bean Paste: A Combined in Silico and in Vitro Study. Food Chem. 2024, 450, 139297. [Google Scholar] [CrossRef]
  101. Zhang, A.; Cui, L.; Tu, X.; Liang, Y.; Wang, L.; Sun, Y.; Kang, X.; Wu, Z. Peptides Derived from Casein Hydrolyzed by Lactobacillus: Screening and Antioxidant Properties in H2O2-Induced HepG2 Cells Model. J. Funct. Foods 2024, 117, 106221. [Google Scholar] [CrossRef]
  102. Guo, H.; Fan, L.; Ding, L.; Yang, W.; Zang, C.; Guan, H. Separation and Purification of Antioxidant Peptide from Fermented Whey Protein by Lactobacillus rhamnosus B2-1. Food Sci. Anim. Resour. 2023, 43, 10–24. [Google Scholar] [CrossRef]
  103. Pavlicevic, M.; Marmiroli, N.; Maestri, E. Immunomodulatory Peptides—A Promising Source for Novel Functional Food Production and Drug Discovery. Peptides 2022, 148, 170696. [Google Scholar] [CrossRef]
  104. Li, B.; Habermann, D.; Kliche, T.; Klempt, M.; Wutkowski, A.; Clawin-Rädecker, I.; Koberg, S.; Brinks, E.; Koudelka, T.; Tholey, A.; et al. Soluble Lactobacillus delbrueckii Subsp. Bulgaricus 92059 PrtB Proteinase Derivatives for Production of Bioactive Peptide Hydrolysates from Casein. Appl. Microbiol. Biotechnol. 2019, 103, 2731–2743. [Google Scholar] [CrossRef]
  105. Xing, L.; Fu, L.; Hao, Y.; Miao, Y.; Zhang, W. Xuanwei Ham Derived Peptides Exert the Anti-Inflammatory Effect in the Dextran Sulfate Sodium-Induced C57BL/6 Mice Model. Food Biosci. 2022, 48, 101800. [Google Scholar] [CrossRef]
  106. Wen, L.; Bi, H.; Zhou, X.; Jiang, Y.; Zhu, H.; Fu, X.; Yang, B. Structure Characterization of Soybean Peptides and Their Protective Activity against Intestinal Inflammation. Food Chem. 2022, 387, 132868. [Google Scholar] [CrossRef]
  107. Vogel, H.J.; Schibli, D.J.; Jing, W.; Lohmeier-Vogel, E.M.; Epand, R.F.; Epand, R.M. Towards a Structure-Function Analysis of Bovine Lactoferricin and Related Tryptophan- and Arginine-Containing Peptides. Biochem. Cell Biol. 2002, 80, 49–63. [Google Scholar] [CrossRef] [PubMed]
  108. Guha, S.; Majumder, K. Structural-Features of Food-Derived Bioactive Peptides with Anti-Inflammatory Activity: A Brief Review. J. Food Biochem. 2019, 43, e12531. [Google Scholar] [CrossRef]
  109. Li, Y.; Gao, X.; Pan, D.; Liu, Z.; Xiao, C.; Xiong, Y.; Du, L.; Cai, Z.; Lu, W.; Dang, Y.; et al. Identification and Virtual Screening of Novel Anti-Inflammatory Peptides from Broccoli Fermented by Lactobacillus strains. Front. Nutr. 2023, 9, 1118900. [Google Scholar] [CrossRef]
  110. Nakamura, Y.; Yamamoto, N.; Sakai, K.; Okubo, A.; Yamazaki, S.; Takano, T. Purification and Characterization of Angiotensin I-Converting Enzyme Inhibitors from Sour Milk. J. Dairy. Sci. 1995, 78, 777–783. [Google Scholar] [CrossRef]
  111. Srivastava, U.; Nataraj, B.H.; Kumari, M.; Kadyan, S.; Puniya, A.K.; Behare, P.V.; Nagpal, R. Antioxidant and Immunomodulatory Potency of Lacticaseibacillus rhamnosus NCDC24 Fermented Milk-Derived Peptides: A Computationally Guided in-Vitro and Ex-Vivo Investigation. Peptides 2022, 155, 170843. [Google Scholar] [CrossRef]
  112. Inoue, K.; Gotou, T.; Kitajima, H.; Mizuno, S.; Nakazawa, T.; Yamamoto, N. Release of Antihypertensive Peptides in Miso Paste during Its Fermentation, by the Addition of Casein. J. Biosci. Bioeng. 2009, 108, 111–115. [Google Scholar] [CrossRef]
  113. Gonzalez-Gonzalez, C.; Gibson, T.; Jauregi, P. Novel Probiotic-Fermented Milk with Angiotensin I-Converting Enzyme Inhibitory Peptides Produced by Bifidobacterium Bifidum MF 20/5. Int. J. Food Microbiol. 2013, 167, 131–137. [Google Scholar] [CrossRef]
  114. Muhialdin, B.J.; Abdul Rani, N.F.; Meor Hussin, A.S. Identification of Antioxidant and Antibacterial Activities for the Bioactive Peptides Generated from Bitter Beans (Parkia speciosa) via Boiling and Fermentation Processes. LWT 2020, 131, 109776. [Google Scholar] [CrossRef]
  115. Quirós, A.; Ramos, M.; Muguerza, B.; Delgado, M.A.; Miguel, M.; Aleixandre, A.; Recio, I. Identification of Novel Antihypertensive Peptides in Milk Fermented with Enterococcus faecalis. Int. Dairy. J. 2007, 17, 33–41. [Google Scholar] [CrossRef]
  116. Arulrajah, B.; Muhialdin, B.J.; Zarei, M.; Hasan, H.; Saari, N. Lacto-Fermented Kenaf (Hibiscus cannabinus L.) Seed Protein as a Source of Bioactive Peptides and Their Applications as Natural Preservatives. Food Control 2020, 110, 106969. [Google Scholar] [CrossRef]
  117. Sanjukta, S.; Rai, A.K.; Muhammed, A.; Jeyaram, K.; Talukdar, N.C. Enhancement of Antioxidant Properties of Two Soybean Varieties of Sikkim Himalayan Region by Proteolytic Bacillus subtilis Fermentation. J. Funct. Foods 2015, 14, 650–658. [Google Scholar] [CrossRef]
  118. Purohit, K.; Reddy, N.; Sunna, A. Exploring the Potential of Bioactive Peptides: From Natural Sources to Therapeutics. Int. J. Mol. Sci. 2024, 25, 1391. [Google Scholar] [CrossRef] [PubMed]
  119. Martínez-Augustin, O.; Rivero-Gutiérrez, B.; Mascaraque, C.; Sánchez de Medina, F. Food Derived Bioactive Peptides and Intestinal Barrier Function. Int. J. Mol. Sci. 2014, 15, 22857–22873. [Google Scholar] [CrossRef] [PubMed]
  120. Hayes, M.; Tiwari, B. Bioactive Carbohydrates and Peptides in Foods: An Overview of Sources, Downstream Processing Steps and Associated Bioactivities. Int. J. Mol. Sci. 2015, 16, 22485–22508. [Google Scholar] [CrossRef] [PubMed]
  121. Ye, H.; Tao, X.; Zhang, W.; Chen, Y.; Yu, Q.; Xie, J. Food-Derived Bioactive Peptides: Production, Biological Activities, Opportunities and Challenges. J. Future Foods 2022, 2, 294–306. [Google Scholar] [CrossRef]
  122. Murtaza, M.A.; Irfan, S.; Hafiz, I.; Ranjha, M.M.A.N.; Rahaman, A.; Murtaza, M.S.; Ibrahim, S.A.; Siddiqui, S.A. Conventional and Novel Technologies in the Production of Dairy Bioactive Peptides. Front. Nutr. 2022, 9, 780151. [Google Scholar] [CrossRef]
  123. Munir, M.; Nadeem, M.; Mahmood Qureshi, T.; Gamlath, C.J.; Martin, G.J.O.; Hemar, Y.; Ashokkumar, M. Effect of Sonication, Microwaves and High-Pressure Processing on ACE-Inhibitory Activity and Antioxidant Potential of Cheddar Cheese during Ripening. Ultrason. Sonochem 2020, 67, 105140. [Google Scholar] [CrossRef]
  124. Xie, M.; Ma, Y.; An, F.; Yu, M.; Zhang, L.; Tao, X.; Pan, G.; Liu, Q.; Wu, J.; Wu, R. Ultrasound-Assisted Fermentation for Antioxidant Peptides Preparation from Okara: Optimization, Stability, and Functional Analyses. Food Chem. 2024, 439, 138078. [Google Scholar] [CrossRef]
  125. Wu, N.; Zhang, F.; Shuang, Q. Peptidomic Analysis of the Angiotensin-Converting-Enzyme Inhibitory Peptides in Milk Fermented with Lactobacillus delbrueckii QS306 after Ultrahigh Pressure Treatment. Food Res. Int. 2023, 164, 112406. [Google Scholar] [CrossRef]
  126. Khakhariya, R.; Basaiawmoit, B.; Sakure, A.A.; Maurya, R.; Bishnoi, M.; Kondepudi, K.K.; Padhi, S.; Rai, A.K.; Liu, Z.; Hati, S. Production and Characterization of ACE Inhibitory and Anti-Diabetic Peptides from Buffalo and Camel Milk Fermented with Lactobacillus and Yeast: A Comparative Analysis with in Vitro, In Silico, and Molecular Interaction Study. Foods 2023, 12, 2006. [Google Scholar] [CrossRef]
  127. Sharma, P.; Sharma, D.; Kaur, S.; Borah, A. Optimization of Flaxseed Milk Fermentation for the Production of Functional Peptides and Estimation of Their Bioactivities. Food Sci. Technol. Int. 2021, 27, 585–597. [Google Scholar] [CrossRef] [PubMed]
  128. Bautista-Expósito, S.; Peñas, E.; Silván, J.M.; Frias, J.; Martínez-Villaluenga, C. PH-Controlled Fermentation in Mild Alkaline Conditions Enhances Bioactive Compounds and Functional Features of Lentil to Ameliorate Metabolic Disturbances. Food Chem. 2018, 248, 262–271. [Google Scholar] [CrossRef] [PubMed]
  129. Akbarbaglu, Z.; Ayaseh, A.; Ghanbarzadeh, B.; Sarabandi, K. Biological Stabilization of Arthrospira Bioactive-Peptides within Biopolymers: Functional Food Formulation; Bitterness-Masking and Nutritional Aspects. LWT 2024, 191, 115653. [Google Scholar] [CrossRef]
  130. Abdo, A.A.A.; Al-Dalali, S.; Hou, Y.; Aleryani, H.; Shehzad, Q.; Asawmahi, O.; AL-Farga, A.; Mohammed, B.; Liu, X.; Sang, Y. Modification of Marine Bioactive Peptides: Strategy to Improve the Biological Activity, Stability, and Taste Properties. Food Bioproc Tech. 2024, 17, 1412–1433. [Google Scholar] [CrossRef]
  131. Atma, Y.; Murray, B.S.; Sadeghpour, A.; Goycoolea, F.M. Encapsulation of Short-Chain Bioactive Peptides (BAPs) for Gastrointestinal Delivery: A Review. Food Funct. 2024, 15, 3959–3979. [Google Scholar] [CrossRef]
  132. Pérez-Pérez, V.; Jiménez-Martínez, C.; González-Escobar, J.L.; Corzo-Ríos, L.J. Exploring the Impact of Encapsulation on the Stability and Bioactivity of Peptides Extracted from Botanical Sources: Trends and Opportunities. Front. Chem. 2024, 12, 1423500. [Google Scholar] [CrossRef]
  133. Lekshmi, R.G.K.; Tejpal, C.S.; Anas, K.K.; Chatterjee, N.S.; Mathew, S.; Ravishankar, C.N. Binary Blend of Maltodextrin and Whey Protein Outperforms Gum Arabic as Superior Wall Material for Squalene Encapsulation. Food Hydrocoll. 2021, 121, 106976. [Google Scholar] [CrossRef]
  134. Sarabandi, K.; Karami, Z.; Akbarbaglu, Z.; Duangmal, K.; Jafari, S.M. Spray-Drying Stabilization of Oleaster-Seed Bioactive Peptides within Biopolymers: Pan-Bread Formulation and Bitterness-Masking. Food Biosci. 2024, 58, 103837. [Google Scholar] [CrossRef]
  135. Wang, Z.; Ju, X.; He, R.; Yuan, J.; Wang, L. The Effect of Rapeseed Protein Structural Modification on Microstructural Properties of Peptide Microcapsules. Food Bioproc. Tech. 2015, 8, 1305–1318. [Google Scholar] [CrossRef]
  136. Thongcumsuk, B.; Woraprayote, W.; Janyaphisan, T.; Cheunkar, S.; Oaew, S. Microencapsulation and Peptide Identification of Purified Bioactive Fraction from Spirulina Protein Hydrolysates with Dipeptidyl Peptidase IV (DPP-IV) Inhibitory Activity. Food Biosci. 2023, 56, 103438. [Google Scholar] [CrossRef]
  137. Gharehbeglou, P.; Homayouni-Rad, A.; Jafari, S.M.; Sarabandi, K.; Akbarbaglu, Z. Stabilization of Chlorella Bioactive Hydrolysates Within Biopolymeric Carriers: Techno-Functional, Structural, and Biological Properties. J. Polym. Environ. 2024, 32, 763–779. [Google Scholar] [CrossRef]
  138. Devi, N.; Sarmah, M.; Khatun, B.; Maji, T.K. Encapsulation of Active Ingredients in Polysaccharide–Protein Complex Coacervates. Adv. Colloid. Interface Sci. 2017, 239, 136–145. [Google Scholar] [CrossRef] [PubMed]
  139. Thapa, R.K.; Kim, J.O. Nanomedicine-Based Commercial Formulations: Current Developments and Future Prospects. J. Pharm. Investig. 2023, 53, 19–33. [Google Scholar] [CrossRef] [PubMed]
  140. Javadi, B.; Farahmand, A.; Soltani-Gorde-Faramarzi, S.; Hesarinejad, M.A. Chitosan-Coated Nanoliposome: An Approach for Simultaneous Encapsulation of Caffeine and Roselle-Anthocyanin in Beverages. Int. J. Biol. Macromol. 2024, 275, 133469. [Google Scholar] [CrossRef]
  141. Mazloomi, S.N.; Mahoonak, A.S.; Ghorbani, M.; Houshmand, G. Physicochemical Properties of Chitosan-Coated Nanoliposome Loaded with Orange Seed Protein Hydrolysate. J. Food Eng. 2020, 280, 109976. [Google Scholar] [CrossRef]
  142. Khalatbari, S.; Hasani, M.; Khoshvaght-Aliabadi, M. Investigating the Characteristics of Nanoliposomes Carrying Bioactive Peptides Obtained from Shrimp Waste. Int. J. Pept. Res. Ther. 2024, 30, 10. [Google Scholar] [CrossRef]
  143. Pateiro, M.; Gómez, B.; Munekata, P.E.S.; Barba, F.J.; Putnik, P.; Kovačević, D.B.; Lorenzo, J.M. Nanoencapsulation of Promising Bioactive Compounds to Improve Their Absorption, Stability, Functionality and the Appearance of the Final Food Products. Molecules 2021, 26, 1547. [Google Scholar] [CrossRef]
  144. Intiquilla, A.; Jiménez-Aliaga, K.; Iris Zavaleta, A.; Gamboa, A.; Caro, N.; Diaz, M.; Gotteland, M.; Abugoch, L.; Tapia, C. Nanoencapsulation of Antioxidant Peptides from Lupinus mutabilis in Chitosan Nanoparticles Obtained by Ionic Gelling and Spray Freeze Drying Intended for Colonic Delivery. Food Biosci. 2022, 50, 102055. [Google Scholar] [CrossRef]
  145. Chen, X.; Fang, F.; Wang, S. Physicochemical Properties and Hepatoprotective Effects of Glycated Snapper Fish Scale Peptides Conjugated with Xylose via Maillard Reaction. Food Chem. Toxicol. 2020, 137, 111115. [Google Scholar] [CrossRef]
Figure 1. Bibliometric analysis of published scientific articles on ‘bioactive peptides from fermented foods’. The search was carried out in PubMed® on articles from 1995 to 2024.
Figure 1. Bibliometric analysis of published scientific articles on ‘bioactive peptides from fermented foods’. The search was carried out in PubMed® on articles from 1995 to 2024.
Foods 13 03369 g001
Figure 2. Schematic representation of BAP production and their associated bioactivities.
Figure 2. Schematic representation of BAP production and their associated bioactivities.
Foods 13 03369 g002
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Peres Fabbri, L.; Cavallero, A.; Vidotto, F.; Gabriele, M. Bioactive Peptides from Fermented Foods: Production Approaches, Sources, and Potential Health Benefits. Foods 2024, 13, 3369. https://doi.org/10.3390/foods13213369

AMA Style

Peres Fabbri L, Cavallero A, Vidotto F, Gabriele M. Bioactive Peptides from Fermented Foods: Production Approaches, Sources, and Potential Health Benefits. Foods. 2024; 13(21):3369. https://doi.org/10.3390/foods13213369

Chicago/Turabian Style

Peres Fabbri, Laryssa, Andrea Cavallero, Francesca Vidotto, and Morena Gabriele. 2024. "Bioactive Peptides from Fermented Foods: Production Approaches, Sources, and Potential Health Benefits" Foods 13, no. 21: 3369. https://doi.org/10.3390/foods13213369

APA Style

Peres Fabbri, L., Cavallero, A., Vidotto, F., & Gabriele, M. (2024). Bioactive Peptides from Fermented Foods: Production Approaches, Sources, and Potential Health Benefits. Foods, 13(21), 3369. https://doi.org/10.3390/foods13213369

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop