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Studies on Lactic Acid Bacteria and Their Products in Health and Diseases: 3rd Edition

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: 20 August 2026 | Viewed by 11779

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Dr. Ilavenil Soundharrajan

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Grassland and Forages Division, National Institute of Animal Science, Rural Development Administration, Cheonan 31000, Republic of Korea
Interests: obesity; muscle cells; adipocytes; biological role of natural compounds
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Dear Colleagues,

Lactic acid bacteria (LAB) are ubiquitous microorganisms that can be found in many natural sources such as plants, mammal’s intestinal mucosa, and fermented foods. They are generally recognized as safe for food applications. Direct supplementation of LAB as probiotics or LAB-driven fermented products poses a wide range of health-promoting effects on molecular and metabolic processes in humans and animals, including protection against infection-causing agents, free radical-scavenging effects, targeting obesity and related metabolic diseases, anti-diabetes activity, immunomodulatory and allergy reaction mediation, anti-cancer effects, prevention of antibiotic-associated complications, reduction in blood pressure, modulation of gut-associated microbial population, enhancing nutrient utilization, etc. Therefore, the current Special Issue will bring together recent research on the role of LAB in the prevention/management of metabolic diseases and disorders, with the aim of producing a better understanding of its biological mechanisms. The different disciplinary topics include but are not limited to the following:

Probiotic LAB;
Nutrition;
Gut-associated microbes;
Metabolic diseases and disorders;
Carbohydrate and fat metabolisms;
Insulin-resistance and sensitivity;
Free radicals, antioxidants, hepatoprotective processes;
Myogenesis, adipogenesis, osteogenesis;
Nutrient utilization;
Immunomodulation and inflammation.

Dr. Ilavenil Soundharrajan
Guest Editor

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Keywords

lactic acid bacteria
probiotics health benefits
gut microbiota modulation
functional foods with biological applications
immunomodulatory mechanisms
antimicrobial peptide production and its mechanisms
host-microbe interactions
functional dairy and meat products
inflammatory bowel diseases
metabolic health improvement
bioactive microbial metabolites
food safety and management
metabolic diseases and disorders
antibiotic-associated complications

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Published Papers (7 papers)

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30 pages, 1009 KB

Open AccessReview

Advances in Genetic Transformation of Lactic Acid Bacteria: Overcoming Barriers and Enhancing Plasmid Tools

by Aleksei S. Rozanov, Leonid A. Shaposhnikov, Kseniya D. Bondarenko and Alexey E. Sazonov

Int. J. Mol. Sci. 2025, 26(18), 9146; https://doi.org/10.3390/ijms26189146 - 19 Sep 2025

Cited by 6 | Viewed by 5523

Abstract

Lactic acid bacteria (LAB) are central to food fermentation, probiotic delivery, and emerging synthetic biology applications, yet their robust cell envelopes and restriction–modification systems complicate DNA uptake. This review synthesizes practical routes for introducing DNA into LAB—natural competence, electroporation, conjugation, phage-mediated transduction, and biolistics—and outlines vector systems for expression and chromosomal editing, including food-grade strategies. We highlight recent advances that broaden strain tractability while noting strain-to-strain variability and host-specific barriers that still require tailored solutions. These advances directly enable applications in food and probiotic biotechnology, including improving starter robustness, tailoring flavor and texture pathways, and installing food-grade traits without residual selection markers. We close with near-term priorities for standardizing protocols, widening replicon compatibility, and leveraging modern genome-editing platforms to accelerate safe, marker-free engineering of industrial and probiotic LAB. Full article

(This article belongs to the Special Issue Studies on Lactic Acid Bacteria and Their Products in Health and Diseases: 3rd Edition)

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16 pages, 5831 KB

Open AccessArticle

Lactiplantibacillus plantarum HY7718 Attenuates Renal Injury in an Adenine-Induced Chronic Kidney Disease Mouse Model via Inhibition of Inflammation and Apoptosis

by Hyeonji Kim, Ji-Woong Jeong, Haeryn Jeong, Daehyeop Lee, Hyeonjun Gwon, Kippuem Lee, Joo-Yun Kim, Jae-Jung Shim and Jae-Hwan Lee

Int. J. Mol. Sci. 2025, 26(20), 10052; https://doi.org/10.3390/ijms262010052 - 15 Oct 2025

Cited by 1 | Viewed by 1289

Abstract

Chronic kidney disease (CKD) causes a variety of health problems including renal dysfunction and cardiovascular disease. This study aimed to investigate whether the probiotic strain Lactiplantibacillus plantarum HY7718 (HY7718) can protect against CKD using HK2 cells and a CKD mouse model, generated by feeding mice a diet containing 0.15% adenine. In vitro tests showed that HY7718 was anti-inflammatory in H₂O₂-treated HK2 cells and reduced apoptosis of tumor necrosis factor-α/cycloheximide-induced HK2 cells. In the adenine-induced CKD model, markers of renal dysfunction (blood urea nitrogen (BUN) and creatinine (Crea)) and inorganic calcium and phosphorus were markedly increased. However, oral administration of HY7718 (10⁸ colony-forming units/kg/day) significantly attenuated these increases. HY7718 also reduced the kidney histopathological score, including tubular necrosis, cast formation, and tubular dilatation, as well as the mononuclear cell infiltration score in kidney tissue, suggesting that it could reverse the progression of CKD. Additionally, HY7718 downregulated the renal expression of pro-inflammatory cytokine genes and members of the TLR/NF-κB signaling pathway. Furthermore, HY7718 reduced tubule apoptotic cells and expression of apoptosis-related genes, indicating that it is potentially renoprotective. These results demonstrate that supplementation with the probiotic HY7718 can ameliorate CKD symptoms by improving renal function and reducing kidney injury. Full article

(This article belongs to the Special Issue Studies on Lactic Acid Bacteria and Their Products in Health and Diseases: 3rd Edition)

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11 pages, 1723 KB

Open AccessBrief Report

Stimulation of Peripheral Blood Mononuclear Cells with Lactococcus lactis Strain Plasma Elicits Antiviral Effects Against H1N1 and SARS-CoV-2

by Zhao Xuan Low, Owen Woo, Osamu Kanauchi, Pouya Hassandarvish, Vunjia Tiong and Sazaly AbuBakar

Int. J. Mol. Sci. 2025, 26(23), 11573; https://doi.org/10.3390/ijms262311573 - 28 Nov 2025

Cited by 1 | Viewed by 998

Abstract

Viruses, like influenza and Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remain major causes of upper respiratory tract infections worldwide, with symptoms ranging from asymptomatic to lethal outcomes. While antivirals and vaccines have helped ameliorate disease morbidity and mortality, these infections still pose significant challenges. Probiotics, including Lactococcus lactis strain plasma (LC-Plasma), have recently shown antiviral effects by activating plasmacytoid dendritic cells (pDCs), though their detailed mechanism remains unclear. In this study, we stimulated peripheral blood mononuclear cells (PBMCs) collected from healthy participants with LC-Plasma and conducted immunological analyses to investigate the immunomodulatory mechanisms of LC-Plasma. The supernatant derived from LC-Plasma-stimulated PBMCs (LCP Sup) exhibited dose-dependent inhibition of replication in Influenza A virus subtype H1N1 (H1N1) and SARS-CoV-2. LCP Sup significantly reduced the SARS-CoV-2 viral load in Huh-7 cells. However, in the H1N1 antiviral assay using A549 cells, LCP Sup was required at a higher concentration against H1N1 in A549 cells compared with SARS-CoV-2 in Huh-7 cells. Treatment with LCP Sup significantly upregulated interferon-stimulated genes (ISG) expression, particularly MxA, in A549 cells. While MxA showed the most notable increase, other ISGs also exhibited elevated expression levels compared with the negative control. Other cytokines, chemokines, and growth factors were also induced by LC-Plasma and CpG-DNA stimulation, and the effects of LC-Plasma were much higher than those of CpG-DNA. These results provide in vitro evidence of the antiviral mechanisms of LC-Plasma via upregulation of interferon-α (IFN-α) and related ISGs for host defense against respiratory viruses. Full article

(This article belongs to the Special Issue Studies on Lactic Acid Bacteria and Their Products in Health and Diseases: 3rd Edition)

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10 pages, 834 KB

Open AccessArticle

The Effect of Cell-Free Metabolites of Vaginal Lactobacilli on HeLa Cells Is Independent of Lactic Acid Concentration

by Yulia Myachina and Andrey Sgibnev

Int. J. Mol. Sci. 2025, 26(24), 11929; https://doi.org/10.3390/ijms262411929 - 11 Dec 2025

Viewed by 711

Abstract

It remains unclear how metabolites produced by vaginal peroxide-producing lactobacilli influence parameters supporting cervical cancer cell survival. The aim of our study was to investigate the functional response of HeLa cells to cell-free metabolites of vaginal lactobacilli producing peroxide under conditions of oxidative stress. HeLa cells were treated with cell-free metabolites of lactobacilli isolated from the vaginal fluid of healthy women. Subsequently, their resistance to oxidative stress (total number of surviving, apoptotic, and necrotic cells), dehydrogenase activity with the MTT assay, and mitochondrial potential were measured. Pretreatment with cell-free lactobacilli metabolites significantly reduced HeLa cell survival under oxidative stress in most cases; dehydrogenase activity and mitochondrial potential changed to a lesser extent. All HeLa cells pretreated with cell-free lactobacillus metabolites that died due to oxidative stress died apoptotic death. These effects of cell-free lactobacilli metabolites are not always determined by lactic acid levels. These data reveal a new mechanism by which vaginal lactobacilli exert local antitumor protection by inducing controlled cell death in transformed cells. Full article

(This article belongs to the Special Issue Studies on Lactic Acid Bacteria and Their Products in Health and Diseases: 3rd Edition)

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17 pages, 1317 KB

Open AccessArticle

Development of the Efficient Electroporation Protocol for Leuconostoc mesenteroides

by Kseniya D. Bondarenko, Leonid A. Shaposhnikov, Aleksei S. Rozanov and Alexey E. Sazonov

Int. J. Mol. Sci. 2025, 26(24), 11933; https://doi.org/10.3390/ijms262411933 - 11 Dec 2025

Viewed by 1270

Abstract

Leuconostoc mesenteroides is a key microorganism in food biotechnology, valued for its production of flavor-forming metabolites and exopolysaccharides, and its inclusion in starter cultures and biocatalytic systems. However, the application of advanced genetic tools to L. mesenteroides remains hindered by multiple barriers, including inefficient DNA transfer, elevated endogenous nuclease activity, and restriction–modification systems sensitive to plasmid methylation patterns. As a result, even widely accepted electroporation methodologies often yield inconsistent or irreproducible transformation results, limiting the strain’s amenability to metabolic engineering and synthetic biology applications. In this study, a reproducible electroporation protocol for the L. mesenteroides strain H32-02 Ksu is developed and experimentally validated. The protocol concept relies on the sequential optimization of key process steps: targeted weakening of the cell wall followed by osmotic protection, the development of a gentle electrical stimulus that ensures membrane permeability without critical damage, and the creation of recovery conditions that minimize loss of viability and degradation of incoming DNA. Matching plasmid methylation to the recipient’s restriction profile proved critical: choosing a source for plasmid DNA production with a compatible methylation pattern dramatically increased the likelihood of successful transformation. In our case, the selection of an E. coli strain with a more suitable methylation profile increased the yield of transformants by 3.5 times. It was also shown that reducing the pulse voltage increase transformant number by 3 times. The combined optimization resulted in an approximately 40-fold increase in transformation efficiency compared to the baseline level and, for the first time, provided consistently reproducible access to transformants of this strain. The highest transformation efficiency was achieved: 8 × 10² CFU µg⁻¹ DNA. The presented approach highlights the strain-specificity of barriers in Leuconostoc and forms a technological basis for constructing strains with desired properties, expressing heterologous enzymes, and subsequently scaling up bioprocesses in food and related industries. The methodological principles embodied in the protocol are potentially transferable to other lactic acid bacteria with similar limitations. Full article

(This article belongs to the Special Issue Studies on Lactic Acid Bacteria and Their Products in Health and Diseases: 3rd Edition)

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22 pages, 3427 KB

Open AccessArticle

Membrane Vesicles from Lactobacillus acidophilus Promote Superior Cytokine Modulation and Antimicrobial Signaling Compared with Their Whole Cells in RAW 264.7 Macrophages

by Cristal Dafne Lonngi Sosa, Francisco Rodolfo González Díaz, Hugo Ramírez Álvarez, Alejandro Vargas Ruiz, Rosa Isabel Higuera Piedrahita, Héctor Alejandro de la Cruz Cruz, Jorge Alfredo Cuéllar Ordaz, Gerardo Ramírez-Rico, Erasmo Negrete Abascal, Magda Reyes López and Cynthia González Ruíz

Int. J. Mol. Sci. 2026, 27(6), 2764; https://doi.org/10.3390/ijms27062764 - 18 Mar 2026

Viewed by 485

Abstract

The interaction between probiotic bacteria and the innate immune system is of increasing interest due to its capacity to modulate inflammatory and antimicrobial responses. The murine macrophage cell line RAW 264.7 is widely used to investigate the immunomodulatory effects of probiotic bacteria and their cell-free derivatives, such as membrane vesicles (MVs). In this study, we evaluated whether MVs derived from Lactobacillus acidophilus promote superior modulation of cytokine production and antimicrobial signaling in RAW 264.7 macrophages compared with whole cells (WCs). Our results show that L. acidophilus MVs exhibited direct bactericidal activity against Escherichia coli and induced a more selective and balanced cytokine profile than whole cells. These findings highlight the potential of probiotic-derived membrane vesicles as acellular immunomodulatory effectors for the development of novel cell-free biotherapeutic strategies. Full article

(This article belongs to the Special Issue Studies on Lactic Acid Bacteria and Their Products in Health and Diseases: 3rd Edition)

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24 pages, 20163 KB

Open AccessArticle

Isolation, Identification, Virulence and Pathogenic Features of Lactococcus garvieae from Cage-Cultured Tilapia (Oreochromis niloticus) in Thailand

by Yosapon Adisornprasert, Benchawan Kumwan, Pakapon Meachasompop, Chonlatat Rajitdumrong, Pimrawee Chaemlek, Prapansak Srisapoome, Wararut Buncharoen, Natthapong Paankhao, Niyada Umputhorn, Chonthicha Choppradit, Pichasit Sangmek, Sittichai Hatachote, Putita Chokmangmeepisarn, Kednapat Sriphairoj and Anurak Uchuwittayakul

Int. J. Mol. Sci. 2026, 27(8), 3469; https://doi.org/10.3390/ijms27083469 - 13 Apr 2026

Viewed by 718

Abstract

Lactococcosis caused by Lactococcus garvieae is an emerging threat to warmwater aquaculture, yet evidence integrating field outbreaks with robust molecular confirmation and controlled virulence testing remains limited for Thailand’s cage-cultured tilapia. From May to October 2025, acute mortality events were investigated in cage-cultured Nile tilapia (Oreochromis niloticus) in a reservoir in Ubon Ratchathani Province, Thailand. Suspected outbreaks were defined by abrupt daily mortality exceeding 5% accompanied by septicemia-like clinical signs. Water quality during sampling covered the following ranges: temperature 28.6–31.9 °C, pH 6.5–7.0, salinity 0.02–0.03 ppt, electrical conductivity 0.036–0.046 mS/cm, TDS 22.20–26.50 mg/L, total alkalinity 17.0–34.0 mg/L as CaCO₃, total hardness 12.0–60.0 mg/L as CaCO₃, dissolved oxygen 6.5–7.0 mg/L, and NH₃ were below the limit of detection. Full-length 16S rRNA tissue profiling revealed strong tissue partitioning: blood microbiomes were consistently dominated by Lactococcus and L. garvieae at the species level, whereas gills showed higher richness and mixed communities with multiple opportunistic taxa. Culture isolation was more reliable from blood than gills, yielding 16 Gram-positive, catalase-negative isolates (AAHM-LG2501–AAHM-LG2516) that clustered within the L. garvieae clade in near full-length 16S rRNA phylogenetic analysis and were separated from closely related Lactococcus lineages. A representative blood isolate (AAHM-LG2501) showed dose-dependent virulence in controlled challenges, with an LD₅₀ of ~1.05 × 10⁵ CFU/fish by intraperitoneal injection and an LC₅₀ of ~1.20 × 10⁶ CFU/mL by immersion. Histopathology supported systemic dissemination, with injection producing more consistent multi-organ lesions than immersion, particularly in head kidney, liver, and spleen, while gills exhibited route-associated epithelial and vascular alterations. Together, these findings confirm L. garvieae as a major etiological agent of septicemic outbreaks in cage-cultured tilapia in Thailand and support a practical surveillance framework prioritizing blood sampling, molecular confirmation, and risk-based monitoring to guide biosecurity and vaccine-oriented prevention. Full article

(This article belongs to the Special Issue Studies on Lactic Acid Bacteria and Their Products in Health and Diseases: 3rd Edition)

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