Search Results (110)

Introduction: The gut microbiota is vital for human health, and its modulation through dietary and pharmaceutical compounds has gained increasing attention. Among gut microbes, Akkermansia muciniphila has been extensively researched due to its role in maintaining intestinal barrier integrity, regulating energy metabolism, and influencing inflammatory responses. Subject: To analyze and synthesize the available scientific evidence on the influence of various bioactive compounds, including prebiotics, polyphenols, antioxidants, and pharmaceutical agents, on the abundance and activity of A. muciniphila, considering underlying mechanisms, microbial context, and its therapeutic potential for improving metabolic and intestinal health. Methods: A systematic literature review was conducted in accordance with the PRISMA 2020 guidelines. Databases such as PubMed, ScienceDirect, Scopus, Web of Science, SciFinder-n, and Google Scholar were searched for publications from 2004 to 2025. Experimental studies in animal models or humans that evaluated the impact of bioactive compounds on the abundance or activity of A. muciniphila were prioritized. The selection process was managed using the Covidence platform. Results: A total of 78 studies were included in the qualitative synthesis. This review compiles and analyzes experimental evidence on the interaction between A. muciniphila and various bioactive compounds, including prebiotics, antioxidants, flavonoids, and selected pharmaceutical agents. Factors such as the chemical structure of the compounds, microbial environment, underlying mechanisms, production of short-chain fatty acids (SCFAs), and mucin interactions were considered. Compounds such as resistant starch type 2, GOS, 2′-fucosyllactose, quercetin, resveratrol, metformin, and dapagliflozin showed beneficial effects on A. muciniphila through direct or indirect pathways. Discussion: Variability across studies reflects the influence of multiple variables, including compound type, dose, intervention duration, experimental models, and analytical methods. These differences emphasize the need for a contextualized approach when designing microbiota-based interventions. Conclusions: A. muciniphila emerges as a promising therapeutic target for managing metabolic and inflammatory diseases. Further mechanistic and clinical studies are necessary to validate its role and to support the development of personalized microbiota-based treatment interventions. Full article

Human milk oligosaccharides (HMOs) have garnered significant attention as one of the bioactive components in human milk, with growing applications in infant formula and food products. HMOs enhance butyrate production, which is produced by butyrate-producing bacteria such as Faecalibacterium prausnitzii and contributes to gut health through its diverse biological functions. However, the specific mechanisms by which individual HMOs promote butyrate production remain unclear. In this study, we conducted in vitro co-culture experiments of F. prausnitzii and Bifidobacterium bifidum, examining their relative abundance, fatty acid production, residual sugar levels, and gene expression. Our results revealed that B. bifidum utilizes HMOs and provides the constituent sugars to F. prausnitzii, thereby promoting butyrate production by F. prausnitzii. Furthermore, we found that the underlying mechanisms vary depending on the structure of the HMOs. Specifically, 2′-fucosyllactose and 3′-sialyllactose enhance the butyrate production efficiency of F. prausnitzii, while 6′-sialyllactose primarily promotes the growth of F. prausnitzii. These findings not only deepen our understanding of how HMOs influence infant gut health but also suggest new directions for developing nutritional products that leverage the distinct functional properties of each HMO. Full article

Background/Objectives: Antibiotics have a significant impact on the gut microbiota, and we hypothesized that human milk oligosaccharides may alleviate antibiotic-induced gut microbiota dysbiosis. Methods: Six groups of eight mice were administered drinking water with or without ampicillin for one week. We then introduced the human milk oligosaccharide 2′-fucosyllactose (2′FL), either alone or in combination with difucosyl-lactose (DFL), for two weeks after the termination of ampicillin treatment. Results: Ampicillin reduced microbiota diversity and the abundance of specific bacteria. One week after the termination of ampicillin treatment, the 2′FL + DFL mixture counteracted the ampicillin-induced reduction in diversity, although this effect was not sustained. Over the subsequent two weeks, the 2′FL + DFL mixture had a significant impact on the relative abundances of Lactobacillus spp. and Bacteroides spp. Ampicillin also reduced caecal propionate levels, downregulated the gene Gzmb for Granzyme B, and upregulated the gene Reg3a for Regenerating islet-derived protein 3 alpha, all of which were counteracted by the 2′FL + DFL mixture. Ampicillin had a minor impact on ileal cytokine levels. The 2′FL + DFL mixture showed a cytokine effect indicating reduced adaptive and innate inflammation. Ampicillin reduced water intake and growth in the mice. The oligosaccharides did not affect water intake, but the 2′FL + DFL mixture slightly reduced body weight. Conclusions: The 2′FL + DFL mixture appears to hold potential for counteracting some of the side effects of ampicillin treatment. Full article

Breast milk is rich in bioactive components, especially human milk oligosaccharides (HMOs), which are crucial for establishing gut microbiota. The 2′-FL (2-Fucosyllactose), one of the most abundant oligosaccharides in breast milk, functions as a selective prebiotic. Objective: To examine the effect of adding 2′-FL (2-Fucosyllactose) to an infant formula containing prebiotic galacto-oligosaccharides (GOSs) and fructo-oligosaccharides (FOSs) on the gut microbiome of healthy formula-fed infants. Methods: This study enrolled infants from three groups: an HMO experimental group (n = 29), a GOS/FOS control group (n = 30), and an exclusively breastfed (breast milk [BM]) reference group (n = 28). Fecal samples from the three groups in the first and fourth months of life were analyzed. The V3 and V4 regions of the 16S rRNA gene were amplified and sequenced on the Illumina MiSeq. ANOVA, Kruskal–Wallis, richness indices (Chao1, Shannon), UniFrac distances, and the Adonis tests were used to perform statistical analyses on the relative abundance of phyla and genera, as well as the alpha and beta-diversity of the gut microbiota. Results: After intervention, Actinobacteriota emerged as the predominant phylum in both the HMO (60.4%) and BM (46.6%) groups. Bifidobacterium and Escherichia-Shigella were identified as the two most abundant bacterial genera in both groups. Nevertheless, the statistical analysis showed that the relative abundance of Bifidobacterium in the HMO formula-fed group after intervention was similar to that in the BM group (p > 0.05). Infants in the HMO and GOS/FOS groups showed higher relative abundance of [Ruminococcus]_gnavus_group bacteria compared to those in the BM group. Groups fed with infant formula demonstrated higher alpha-diversity of gut microbiota compared to breastfed infants (p < 0.05), at the time of admission as well as after the intervention. Beta-diversity was significantly different among the three groups, according to type of feeding. Infants fed a 2′-FL-supplemented infant formula exhibited growth comparable to that of breastfed infants throughout the intervention period, demonstrating that the formula was both safe and well tolerated. Conclusions: Adding 2′-FL to an infant formula containing 4 g/L of GOS + FOS resulted in a stronger bifidogenic effect compared to the formula without 2′-FL. Full article

Background: The human gut microbiota develops in concordance with its host over a lifetime, resulting in age-related shifts in community structure and metabolic function. Little is known about whether these changes impact the community’s response to microbiome-targeted therapeutics. Providing critical information on this subject, faecal microbiomes of subjects from six age groups, spanning from infancy to 70-year-old adults (n = six per age group) were harvested. The responses of these divergent communities to treatment with the human milk oligosaccharide 2’-fucosyllactose (2’FL), fructo-oligosaccharides (FOS), and lactose was investigated using the Ex vivo SIFR^® technology that employs bioreactor fermentation and is validated to be predictive of clinical findings. Additionally, it was evaluated whether combining faecal microbiomes of a given age group into a single pooled microbiome produced similar results as the individual microbiomes. Results: First, marked age-dependent changes in community structure were identified. Bifidobacterium levels strongly declined as age increased, and Bifidobacterium species composition was age-dependent: B. longum, B. catenulatum/pseudocatenulatum, and B. adolescentis were most prevalent for breastfed infants, toddlers/children, and adults, respectively. Metabolomic analyses (LA-REIMS) demonstrated that these age-dependent differences particularly impacted treatment effects of 2’FL (more than FOS/lactose). Further analysis revealed that while 2’FL enhanced production of short-chain fatty acids (SCFAs) and exerted potent bifidogenic effects, regardless of age, the specific Bifidobacterium species enhanced by 2’FL, as well as subsequent cross-feeding interactions, were highly age-dependent. Furthermore, single-pooled microbiomes produced results that were indicative of the average treatment response for each age group. Nevertheless, pooled microbiomes had an artificially high diversity, thus overestimating treatment responses (especially for infants), did not recapitulate interindividual variation, and disallowed for the correlative analysis required to unravel mechanistic actions. Conclusions: Age is an important factor in shaping the gut microbiome, with the dominant taxa and their metabolites changing over a lifetime. This divergence affects the response of the microbiota to therapeutics, demonstrated in this study using 2’FL. These results evidence the importance of screening across multiple age groups separately to provide granularity of how therapeutics impact the microbiome and, consequently, human health. Full article

Infants rely on their developing immune system and the protective components of breast milk to defend against bacterial and viral pathogens, as well as immune disorders such as food allergies, prior to the introduction of solid foods. When breastfeeding is not feasible, fortified infant formula will most frequently be offered, usually based on a cow’s milk-based substitute. The current study aimed to explore the immunomodulatory effects of combinations of commercially available human milk oligosaccharides (HMOs). An in vitro co-culture model of Caco-2 intestinal epithelial cells and THP-1 macrophages was established to replicate the hallmarks of intestinal inflammation and to evaluate the direct effects of different synthetic HMO combinations. Notably, a blend of the most prevalent fucosylated and sialylated HMOs, 2′-fucosyllactose (2′-FL) and 6′-siallylactose (6′-SL), respectively, resulted in decreased pro-inflammatory cytokine levels. These effects were dependent on the HMO concentration and on the HMO ratio resembling those in breastmilk. Interestingly, adding additional HMO structures did not enhance the anti-inflammatory effects. This research highlights the importance of carefully selecting HMO combinations in nutritional products, particularly for infant milk formulations, to effectively mimic the benefits associated with breastmilk. Full article

Obejectives: This study explored the immunomodulatory effects of a prebiotic formula consisting of 2′-fucosyllactose (2′-FL), galacto-oligosaccharides (GOSs), and fructo-oligosaccharides (FOSs) (hereinafter referred to as 2FGF) in cyclophosphamide (CTX)-induced immunosuppressed BALB/c mice and its underlying mechanisms. Methods: Sixty healthy female BALB/c mice were randomly divided into the following groups: normal control (NC) group; CTX treatment (CTX) group; 2FGF low-dose (2FGF-L) group; 2FGF medium-dose (2FGF-M) group; and 2FGF high-dose (2FGF-H) group. An immunosuppressed model was established in the 2FGF-H group by intraperitoneal injection of 80 mg/kg CTX. After 30 days of 2FGF intervention, peripheral blood, spleen tissue, thymus tissue, and intestinal tissue from the mice were collected and analyzed. The changes in weight and food intake of the mice were recorded weekly. Hematoxylin-eosin (HE) staining was used to observe the histological change of the spleen tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to detect cytokine levels in peripheral blood. Flow cytometry was used to analyze T lymphocyte subgroup ratio of splenic lymphocytes. Western blot analysis was conducted on intestinal tissues to assess the expression of proteins involved in the tight junction, toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathways. Additionally, molecular techniques were used to analyze the intestinal microbiota. Results: The results showed that 2FGF restored CTX-induced splenic injury, increased the number of splenic T lymphocytes, and elevated serum cytokines such as interleukin-4 (IL-4) and IL-10. In the intestine, 2FGF upregulated the expression of intestinal epithelial tight junction proteins such as Claudin-1 and zonula occludens 1 (ZO-1), thereby enhancing intestinal barrier function and activating the MAPK and NF-κB pathways via TLR4. Furthermore, 2FGF elevated the α-diversity (Shannon and Simpson indices) of the gut microbiota in CTX-induced immunosuppressed mice, enriching bacteria species positively correlated with anti-inflammatory cytokines (e.g., IL-4) such as g_Streptomyces and g_Bacillus and negatively correlated with pro-inflammatory cytokines (e.g., IL-1β) such as g_Saccharomyces. The results suggest that 2FGF may enhance immunity via the gut–immune axis. Conclusions: The 2FGF prebiotic formula showed an immunomodulatory effect in CTX-induced immunosuppressed mice, and the mechanism of which might involve optimizing the gut flora, enhancing intestinal homeostasis, strengthening the intestinal barrier, and promoting the expression of immune factors by regulating the TLR-4/MAPK/NF-κB pathway. Full article

Background: 2′-Fucosyllactose (2′-FL) is an oligosaccharide contained in human milk and possesses prebiotic and anti-inflammatory effects, which may alleviate skeletal muscle atrophy under caloric restriction. This study evaluated the impacts of 12 weeks of 2′-FL supplementation in conjunction with exercise (10,000 steps/day, 5 days/week) and energy-reduced (−300 kcals/day) dietary interventions on changes in body composition and health-related biomarkers. Methods: A total of 41 overweight and sedentary female and male participants (38.0 ± 13 years, 90.1 ± 15 kg, 31.6 ± 6.6 kg/m², 36.9 ± 7% fat) took part in a randomized, double-blind, and placebo-controlled study. The participants underwent baseline assessments and were then assigned to ingest 3 g/day of a placebo (PLA) or Momstamin 2′-F while initiating the exercise and weight-loss program. Follow-up tests were performed after 6 and 12 weeks. Data were analyzed using general linear model statistics with repeated measures and mean changes from baseline values with 95% confidence intervals (CIs). Results: No group × time × sex interaction effects were observed, so group × time effects are reported. Participants in both groups saw comparable reductions in weight. However, those with 2′-FL demonstrated a significantly greater reduction in the percentage of body fat and less loss of the fat-free mass. Additionally, there was evidence that 2′-FL supplementation promoted more favorable changes in resting fat oxidation, peak aerobic capacity, IL-4, and platelet aggregation, with some minimal effects on the fermentation of short-chain fatty acids and monosaccharides in fecal samples. Moreover, participants’ perceptions regarding some aspects of the functional capacity and ratings of the quality of life were improved, and the supplementation protocol was well tolerated, although a small, but significant, decrease in BMC was observed. Conclusions: The results support contentions that dietary supplementation of 2′-FL (3 g/d) can promote fat loss and improve exercise- and diet-related markers of health and fitness in overweight sedentary individuals initiating an exercise and weight-loss program. Further research is needed to explore the potential health benefits of 2′-FL supplementation in both healthy and elderly individuals (Registered clinical trial #NCT06547801). Full article

The prevalence of pediatric inflammatory bowel disease (pIBD) has been increasing over the last two decades. Yet, treatment strategies are still limited, in part due to the multifactorial nature of the disease and the complex interplay between genetic, environmental, dietary, immune, and gut microbial factors in its etiology. With their direct and indirect anti-inflammatory properties, human milk oligosaccharides (HMOs) are a promising treatment and management strategy for IBD. However, to date there are no insights into how HMOs may affect pIBD microbiota. Here, we compared the effects of 2′fucosyllactose (2′FL), difucosyllactose (DFL), 3′sialyllactose (3′SL), and blends thereof with fructooligosaccharide (FOS) on microbiota functionality (short- and branched-chain fatty acids, pH, and gas production) and composition (quantitative shallow shotgun sequencing) using fecal material from eight different pediatric Crohn’s disease patients inoculated in the SIFR^® technology. In general, all HMO treatments significantly increased total short-chain fatty acid production when compared with FOS, despite equal gas production. We found that 2′FL, either alone or in combination with DFL and 3′SL, exhibited a strong acetogenic and propiogenic effect, and 3′SL an acetogenic effect that surpassed the effects observed with FOS. No differences in overall community diversity between HMO- and FOS-treated pIBD microbiota were observed. There was, however, a stronger bifidogenic effect of 2′FL, 3′SL, 2′FL/DFL, and 2′FL/DFL + 3′SL when compared with FOS. In general, 3′SL and HMO blends enriched a broader species profile, including taxa with potentially anti-inflammatory properties, such as Faecalibacterium prausnitzii and Blautia species. This study suggests HMOs as a promising strategy to beneficially alter the gut microbial profile in pIBD. Full article

Listeria monocytognes is an emerging pathogen responsible for the serious foodborne disease, listeriosis. The commensal gut microbiota is the first line of defense against pathogen internalization. The gut microbiome can be modified by prebiotic substrates, which are frequently added to food products and dietary supplements. Prebiotics should selectively support the growth of beneficial microbes and thus improve host health. Nevertheless, little is known about their effect on the growth of L. monocytogenes. The aim of this study was to evaluate the growth ability of four L. monocytogenes strains, representing the most common serotypes, on prebiotic oligosaccharides (beta-(1,3)-D-glucan, inulin, fructooligosaccharides, galactooligosaccharides, lactulose, raffinose, stachyose and 2′-fucosyllactose and a mixture of human milk oligosaccharides) as a sole carbon source. The results showed that only beta-(1,3)-D-glucan was metabolized by L. monocytogenes. These cell culture data suggest that beta-(1,3)-D-glucan may not be selectively utilized by healthy commensal bacteria, and its role in intestinal pathogen growth warrants further exploration in vivo. Full article

Background: Human milk oligosaccharides (HMOs), which are unique bioactive components in human milk, are increasingly recognized for their multifaceted roles in infant health. A deeper understanding of the nexus between HMOs and the gut–brain axis can revolutionize neonatal nutrition and neurodevelopmental strategies. Methods: We performed a narrative review using PubMed, Embase, and Google Scholar to source relevant articles. The focus was on studies detailing the influence of HMOs on the gut and brain systems, especially in neonates. Articles were subsequently synthesized based on their exploration into the effects and mechanisms of HMOs on these interconnected systems. Results: HMOs significantly influence the neonatal gut–brain axis. Specific concentrations of HMO, measured 1 and 6 months after birth, would seem to agree with this hypothesis. HMOs are shown to influence gut microbiota composition and enhance neurotransmitter production, which are crucial for brain development. For instance, 2′-fucosyllactose has been demonstrated to support cognitive development by fostering beneficial gut bacteria that produce essential short-chain fatty acids. Conclusions: HMOs serve as crucial modulators of the neonatal gut–brain axis, underscoring their importance in infant nutrition and neurodevelopment. Their dual role in shaping the infant gut while influencing brain function presents them as potential game-changers in neonatal health strategies. Full article

Background: Given the lack of an ideal endodontic irrigant on the market, this study evaluates the antimicrobial potential of a formulated solution of 2′-fucosyllactose and lacto-N-neotetraose against E. faecalis within infected root canals, and explores any associated impacts related to the duration of irrigation. Methods: 32 single-rooted teeth extracted for periodontal reasons were infected with Enterococcus faecalis, and subsequently subjected to endodontic treatment with two different irrigation systems: sodium hypochlorite or a solution of 2′-fucosyllactose and lacto-N-neotetraose. These samples were then incubated in sterile culture media at 37 °C to observe microbial activity through turbidity. The culture broth of each individual sample was assessed as positive or negative by observing the turbidity or lack of turbidity in the culture at the time of evaluation. Results: the analysis of the results obtained from the comparison of groups irrigated with sodium hypochlorite or a solution of 2′-fucosyllactose and lacto-N-neotetraose demonstrates that the case solution has no bactericidal effect against E. faecalis inoculated in the endodontic system. Conclusions: the HMOs used in this study do not have a bactericidal effect on E. faecalis inoculated in an endodontic system. Full article

Background: The purpose of this research was to assess the growth, tolerance, and compliance outcomes associated with the consumption of a hydrolyzed rice infant formula (HRF) enriched with 2′-Fucosyllactose (2′-FL) a Human Milk Oligosaccharide (HMO), and nucleotides in an intended population of infants. Methods: This was a non-randomized single-group, multicenter study. The study formula was a hypoallergenic HRF with 2′-FL, Docosahexaenoic acid (DHA), Arachidonic acid (ARA), and nucleotides. Infants 0–90 days of age who were formula fed and experiencing persistent feeding intolerance symptoms, symptoms of suspected food protein (milk and/or soy) allergy, or other conditions where an extensively hydrolyzed infant formula was deemed an appropriate feeding option were recruited by pediatricians from their local populations. The primary outcome was maintenance of weight-for-age z-score. Weight, length, head circumference, formula intake, tolerance measures, clinical symptoms and questionnaires were collected. Thirty-three infants were enrolled, and 27 completed the study, on study product. Results: Weight-for-age z-scores of infants showed a statistically significant improvement from Visit 1 to Visit 4 (p = 0.0331). There was an adequate daily volume intake of 762 ± 28 mL/day, average daily number of stools of 2.1 ± 0.3, and mean rank stool consistency of 2.38 ± 0.18. After 28 days of switching to a HRF, 86.8 ± 5.9% of the symptoms resolved or got better by Visit 4 as reported by parents. Conclusions: HRF with 2′-FL HMO was safe, well tolerated, and supported weight gain in infants with suspected cow’s milk allergy or persistent feeding intolerance. Full article

Growing evidence indicates that human milk oligosaccharides (HMOs) are important bioactive compounds that enhance health and developmental outcomes in breastfed babies. Maternal dietary intake likely contributes to variation in HMO composition, but studies identifying diet–HMO relationships are few and inconsistent. This study aimed to investigate how the maternal intake of macronutrients and micronutrients—specifically proteins, fats, vitamins, and minerals—associated with HMOs at 1 month (n = 210), 6 months (n = 131), and 12 months postpartum (n = 84). Several associations between maternal dietary factors and HMO profiles were identified utilizing partial correlation analysis. For example, maternal free sugar (rho = −0.02, p < 0.01), added sugar (rho = −0.22, p < 0.01), and sugary sweetened beverage (rho = −0.22, p < 0.01) intake were negatively correlated with the most abundant HMO, 2′-fucosyllactose (2′-FL), at 1 month, suggesting that higher sugar consumption was associated with reduced levels of 2′-FL. Further, vitamins D, C, K, and the minerals zinc and potassium were positively correlated with 2′-FL at 1 month (p_All < 0.05). For the longitudinal analysis, a mixed-effects linear regression model revealed significant associations between maternal vitamin intake and HMO profiles over time. For example, for each unit increase in niacin intake, there was a 31.355 nmol/mL increase in 2′-FL concentration (p = 0.03). Overall, the results provide additional evidence supporting a role for maternal nutrition in shaping HMO profiles, which may inform future intervention strategies with the potential of improving infant growth and development through optimal HMO levels in mothers’ milk. Full article

Human milk oligosaccharides (HMOs) are complexes that play a crucial role in shaping the early-life gut microbiota. This study intends to explore whether HMO patterns are associated with the gut microbiota of infants. We included 96 Chinese breastfeeding mother–infant dyads. Breast milk and infant faecal samples were collected and tested. With milk 2′-fucosyllactose, difucosyllactose, and lacto-N-fucopentaose-I as biomarkers, we divided the mothers into secretor and non-secretor groups. HMO patterns were extracted using principal component analysis. The majority (70.7%) of mothers were categorised as secretor and five different HMO patterns were identified. After adjustment, the infants of secretor mothers exhibited a lower relative abundance of Bifidobacterium bifidum (β = −0.245, 95%CI: −0.465~−0.025). An HMO pattern characterised by high levels of 3-fucosyllactose, lacto-N-fucopentaose-III, and lacto-N-neodifucohexaose-II was positively associated with the relative abundance of Bifidobacterium breve (p = 0.014), while the pattern characterised by lacto-N-neotetraose, 6′-sialyllactose, and sialyllacto-N-tetraose-b was negatively associated with Bifidobacterium breve (p = 0.027). The pattern characterised by high levels of monofucosyl-lacto-N-hexaose-III and monofucosyl-lacto-N-neohexaose was positively associated with Bifidobacterium dentium (p = 0.025) and Bifidobacterium bifidum (p < 0.001), respectively. This study suggests that HMO patterns from mature breast milk were associated with certain gut microbiota of breastfed infants. Full article