Chronic low-grade inflammation and hyperinsulinemia are linked with metabolic dysfunction and dysbiosis. This study investigated the role of dietary inflammatory and insulinemic potential on gut microbiome and circulating health biomarkers in older men. Data from the Osteoporotic Fractures in Men (MrOS) study were analyzed. Reversed Empirical Dietary Inflammatory Pattern (rEDIP), Empirical Dietary Index for Hyperinsulinemia (rEDIH), and Healthy Eating Index (HEI)-2020 scores were computed from food frequency questionnaire data. Stool samples were profiled using 16S rRNA sequencing. Elastic net regression identified diet-associated microbial profiles and multivariable-adjusted linear regression assessed diet-biomarker associations. Higher rEDIP, rEDIH, and HEI-2020 scores were positively associated with gut microbiota alpha diversity. Specific genera, including Intestinibacter and Lachnospira, associated positively, while Dielma, Peptococcus, Feacalitalea, and Negativibaccilus associated inversely with healthier dietary patterns. When evaluating changes in dietary patterns between baseline and visit 4 ( ~ 14 years), these genera tended to define rEDIP, rEDIH more than HEI-2020. In addition, higher dietary quality was linked to better biomarker profiles, including lower creatinine, sodium, triglycerides, and insulin resistance. Beneficial effects of higher dietary quality on health may be mediated by the ability of diet to regulate gut microbial composition and metabolic biomarker profiles.

Osteoporosis is a systemic skeletal disease that leads to lower bone mineral density and intensifies the risk of unexpected fractures. Recently, our group reported that numerical defect in the frequencies of Bregs along with their compromised tendency to produce IL-10 cytokine further aggravates inflammatory bone loss in post-menopausal osteoporosis (PMO). Dysbiosis induced mucosal injury and leaky gut are the predominant contributors involved in the progression of inflammatory diseases including PMO. Furthermore, several evidence suggest that gut microbial composition plays a crucial role in the development and differentiation of Bregs. Nevertheless, the potential role of dysbiotic gut microbiota (GM) and Bregs under estrogen deficient PMO conditions has never been deciphered. Here, we evaluated the role of GM in the onset and progression of PMO along with its role in modulating the anti-osteoporotic potential of Bregs. We found that enhancement in the endotoxin producing bacteria and concomitant reduction in the short chain fatty acids producing bacteria, both under pre-clinical and clinical osteoporotic condition augment inflammatory bone loss. This suggests that dysbiosis of GM potentially exacerbates bone deterioration under estrogen deficient PMO conditions. Remarkably, supplementation of probiotic Bacillus coagulans significantly improved the bone mineral density, bone strength, and bone microarchitecture by modulating the anti-osteoclastogenic, immunosuppressive and immunomodulatory potential of Bregs. The present study delves deeper into the role of immune homeostasis ("Breg-Treg-Th17" cell axis) and GM profile in the pathophysiology of PMO. Altogether, findings of the present study open novel therapeutic avenues, suggesting restoration of GM composition as one of the viable therapeutic options in mitigating inflammatory bone loss under PMO conditions via modulating the "Gut-Immune-Bone" axis.

The human gut microbiota has gained interest as an environmental factor that contributes to health or disease. The development of next-generation live biotherapeutic products (LBPs) is a promising strategy to modulate the gut microbiota and improve human health. In this study, we identified a novel cross-feeding interaction between Bacteroides xylanisolvens and Clostridium butyricum and developed their combination into a novel LBP for treating metabolic syndrome. Using in-silico analysis and in vitro experiments, we demonstrated that B. xylanisolvens supported the growth and butyrate production of C. butyricum by supplying folate, while C. butyricum reciprocated by providing pABA for folate biosynthesis. Animal gavage experiments showed that the two-strain combination LBP exhibited superior therapeutic efficacy against metabolic disorders in high-fat diet-induced obese (DIO) mice compared to either single-strain treatment. Further omics-based analyses revealed that the single-strain treatments exhibited distinct taxonomic preferences in modulating the gut microbiota, whereas the combination LBP achieved more balanced modulation to preserve taxonomic diversity to a greater extent, thereby enhancing the stability and resilience of the gut microbiome. Moreover, the two-strain combinations more effectively restored gut microbial functions by reducing disease-associated pathways and opportunistic pathogen abundance. This work demonstrates the development of new LBP therapy for metabolic diseases from cross-feeding microbial pairs which exerted better self-stability and robust efficacy in complex intestinal environments compared to conventional single-strain LBPs.

Campylobacter jejuni, non-typhoidal Salmonella spp., Listeria monocytogenes and enteropathogenic/enterohemorrhagic Escherichia coli (EPEC/EHEC) are leading causes of food-borne illness worldwide. Citrobacter rodentium has been used to model EPEC and EHEC infection in mice. The gut microbiome is well-known to affect gut colonization and host responses to many food-borne pathogens. Recent progress has established gnotobiotic mice as valuable models to study how microbiota affect the enteric infections by S. Typhimurium, C. rodentium and L. monocytogenes. However, for C. jejuni, we are still lacking a suitable gnotobiotic mouse model. Moreover, the limited comparability of data across laboratories is often negatively affected by variations between different research facilities or murine microbiotas. In this study, we applied the standardized gnotobiotic OligoMM12 microbiota mouse model and compared the infections in the same facility. We provide evidence of robust colonization and significant pathological changes in OligoMM12 mice following infection with these pathogens. Moreover, we offer insights into pathogen-specific host responses and metabolite signatures, highlighting the advantages of a standardized mouse model for direct comparisons of factors influencing the pathogenesis of major food-borne pathogens. Notably, we reveal for the first time that C. jejuni stably colonizes OligoMM12 mice, triggering inflammation. Additionally, our comparative approach successfully identifies pathogen-specific responses, including the detection of genes uniquely associated with C. jejuni infection in humans. These findings underscore the potential of the OligoMM12 model as a versatile tool for advancing our understanding of food-borne pathogen interactions.

The gut microbiota transforms energy stored as undigestible carbohydrates into a remarkable number of metabolites that fuel intestinal bacterial communities and the host tissue. Colonic epithelial cells at the microbiota-host interface depend upon such microbiota-derived metabolites (MDMs) to satisfy their energy requisite. Microbial dysbiosis eliciting MDM loss contributes to barrier dysfunction and mucosal disease. Recent work has identified a role for microbiota-sourced purines (MSPs), notably hypoxanthine, as an MDM salvaged by the colonic epithelium for nucleotide biogenesis and energy balance. Here, we investigated the role of MSPs in mice during disease-modeled colonic energetic stress using a strain of E. coli genetically modified for enhanced purine nucleobase release (E. coli Mutant). E. coli Mutant colonization protected against DSS-induced tissue damage and permeability while promoting proliferation for wound healing. Metabolite and metagenomic analyses suggested a colonic butyrate-purine nucleobase metabolic axis, wherein the E. coli Mutant provided purine substrate for Clostridia butyrate production and host purine salvage, altogether supplying the host substrate for efficient nucleotide biogenesis and energy balance.

Diet is one of the main factors shaping the human microbiome, yet our understanding of how specific dietary components influence microbial consortia assembly and subsequent stability in response to press disturbances - such as increasing resource availability (feeding rate) - is still incomplete. This study explores the reproducible re-assembly, metabolic interplay, and compositional stability within microbial consortia derived from pooled stool samples of three healthy infants. Using a single-step packed-bed reactor (PBR) system, we assessed the reassembly and metabolic output of consortia exposed to lactose, glucose, galacto-oligosaccharides (GOS), and humanized GOS (hGOS). Our findings reveal that complex carbohydrates, especially those containing low inclusion (~1.25 gL-1) components present in human milk, such as N-acetyl-lactosamine (LacNAc), promote taxonomic, and metabolic stability under varying feeding rates, as shown by diversity metrics and network analysis. Targeted metabolomics highlighted distinct metabolic responses to different carbohydrates: GOS was linked to increased lactate, lactose to propionate, sucrose to butyrate, and CO2, and the introduction of bile salts with GOS or hGOS resulted in butyrate reduction and increased hydrogen production. This study validates the use of single-step PBRs for reliably studying microbial consortium stability and functionality in response to nutritional press disturbances, offering insights into the dietary modulation of microbial consortia and their ecological dynamics.

Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus; however, many patients respond poorly to this drug in clinical practice. The potential involvement of microbiota-mediated intestinal immunity and related signals in metformin responsiveness has not been previously investigated. In this study, we successfully constructed a humanized mouse model by fecal transplantation of the gut microbiota from clinical metformin-treated - responders and non-responders, and reproduced the difference in clinical phenotypes of responsiveness to metformin. The abundance of Bacteroides thetaiotaomicron, considered a representative differential bacterium of metformin responsiveness, and the level of secretory immunoglobulin A (SIgA) in intestinal immunity increased significantly in responder recipient mice following metformin treatment. In contrast, no significant alterations in B. thetaiotaomicron and SIgA were observed in non-responder recipient mice. The study of IgA-/- mice confirmed that downregulated expression or deficiency of SIgA resulted in non-response to metformin, meaning that metformin was unable to improve dysfunctional glucose metabolism and reduce intestinal and adipose tissue inflammation, ultimately leading to systemic insulin resistance. Furthermore, supplementation with succinate, a microbial product of B. thetaiotaomicron, potentially reversed the non-response to metformin by inducing the production of SIgA. In conclusion, we demonstrated that upregulated SIgA, which could be regulated by succinate, was functionally involved in metformin response through its influence on immune cell-mediated inflammation and insulin resistance. Conversely, an inability to regulate SIgA may result in a lack of response to metformin.

Roseburia intestinalis is one of the most abundant and important butyrate-producing human gut anaerobic bacteria that plays an important role in maintaining health and is a potential next-generation probiotic. We investigated the pangenome of 16 distinct strains, isolated over several decades, identifying local and time-specific adaptations. More than 50% of the genes in each individual strain were assigned to the core genome, and 77% of the cloud genes were unique to individual strains, revealing the high level of genome conservation. Co-carriage of the same enzymes involved in carbohydrate binding and degradation in all strains highlighted major pathways in carbohydrate utilization and reveal the importance of xylan, starch and mannose as key growth substrates. A single strain had adapted to use rhamnose as a sole growth substrate, the first time this has been reported. The ubiquitous presence of motility and sporulation gene clusters demonstrates the importance of these phenotypes for gut survival and acquisition of this bacterium. More than half the strains contained functional, potentially transferable, tetracycline resistance genes. This study advances our understanding of the importance of R. intestinalis within the gut ecosystem by elucidating conserved metabolic characteristics among different strains, isolated from different locations. This information will help to devise dietary strategies to increase the abundance of this species providing health benefits.

Despite the importance of the gut microbiome on physical performance and health, little is known on the impact of training on an athlete's gut health.

This study investigates the effect of training load on markers of gut health.

Whole stool (24 h) samples were collected from 23 highly trained rowers (mean ± SD; age 19.2 ± 1.1 y; weight 80.1 ± 11.4 kg; height 1.83 ± 0.09 m) following periods of high (HT) and low training load (LT). The microbiome and short-chain fatty acid concentrations were characterized from the whole stool samples. Three-day weighted food records were used to determine diet quality (ADIcore), macronutrient, and fiber intakes during HT and LT.

By design, training duration (147%) and intensity (130%) were greater during (HT), compared with (LT) (p < 0.001). Carbohydrate, fat, protein, and fiber intake remained stable, but ADIcore was higher in HT (55 ± 10) compared with LT (49 ± 9; t(15) = 2.78, p = 0.014; CI: 1.34 to 10.155). Stool frequency (1.11 ± 0.47 vs 0.67 ± 0.76; p = 0.007) was lower in HT compared with LT, and a greater number of participants were unable to produce a stool sample during LT (8% vs 47%). Short chain fatty acid (SCFA), propionic (120.64 ± 30.06 mm vs 91.35 ± 34.91 mm; p = 0.007), and butyric acid (104.76 ± 50.02 vs 64.23 ± 22.05 mm, p = 0.003) concentrations were lower in HT compared with LT. Alpha diversity, Shannon-Wiener diversity index (3.43 ± 0.37 vs 3.67 ± 0.34, p = 0.09) was lower in HT than LT. The abundance of the dominant Bacteroidia was greater at HT compared to LT and ratio of firmicutes to Bacteroidota (n = 16, 1.31 ± 1.19 vs 4.29 ± 3.88, t(15) = -3.44, p = 0.04, CI = -4.82 to -1.13) was lower in HT compared to LT.

Results of this study indicate that gut microbiome, SCFA concentrations, stool frequency, and diet quality vary between periods of high and low training load in athletes. The relationship between these factors and impact of such changes in gut health is currently unclear and warrants further investigation.

The purpose of this study is to investigate the impact of a high-salt diet (HSD), which is commonly found in Western countries, on the progression of glioma. Our research shows that the alterations in gut microbiota caused by an HSD facilitated the development of glioma. Mice fed an HSD have elevated levels of intestinal propionate, which accelerated the growth of glioma cells. We also find that propionate supplementation enhanced the response of glioma cells to low oxygen levels. Moreover, we identify a link between TGF-β signaling, response to low oxygen levels, and invasion-related pathways. Propionate treatment increases the expression of HIF-1α, leading to an increase in TGF-β1 production. Additionally, propionate treatment promotes glioma cell invasion through TGF-β signaling. Our findings suggest that an HSD-induced increase in propionate plays a crucial role in glioma progression by facilitating invasion through the hypoxic response and TGF-β signaling pathways, thereby establishing a significant connection between gut microbiota and the progression of glioma.

Chronic infection with Toxoplasma gondii (T. gondii) results in severe damages to the integrity of intestinal barrier, however, both the underlying mechanism and feasible intervention strategies are still little known. Here, we found that both the chronic infection of T. gondii and transplanting gut microbiota from T. gondii-infected mice severely impaired the mice intestinal integrity, which was characterized by significantly decreased thickness of inner mucus layer and down-regulated expression of three tight junction proteins Occludin, ZO-1, and Claudin (p < 0.05). Moreover, T. gondii infection also led to mice intestinal microbiota dysbiosis, especially butyrate-producing bacteria, and significantly changed the expression of several senescence-associated markers, including 6- and 7- fold upregulation for P16, P21, and 6-fold downregulation for Lamin B1 at mRNA levels, and 2-fold downregulation for β-galactosidase at protein levels (p < 0.05). Interestingly, subsequent administration with dietary butyrate could alleviate T. gondii-induced intestinal integrity impairment and cell senescence, revealing a significant increase of the inner mucus layer thickness (p < 0.001), and a remarkable decrease in P16, P21, β-galactosidase expression levels while an upregulation of Lamin B1 expression (p < 0.05). Taken together, our study revealed that T. gondii-induced dysbiosis of gut microbiota, especially butyrate-producing bacteria, contributes to the intestinal impairment, potentially via promoting cell senescence. In addition, administration with the metabolite, butyrate, could be a promising therapeutic measure against T. gondii infection.

Endometrial cancer (EC) is a significant global health concern. While observational epidemiological studies suggest a potential link between gut microbiota dysbiosis and the development of EC, the direction and causality of this association remain uncertain.

We performed Mendelian randomization (MR) analysis to investigate the causal relationship between gut microbiota and EC. Exposure data were obtained from the MiBioGen study consortium (N = 18,340), and outcome data were sourced from the IEU OpenGWAS database, specifically datasets "ebi-a-GCST006464" (N = 121,885) and "bbj-a-113" (N = 90,730). The inverse variance-weighted(IVW) method was applied to evaluate the association between gut microbiota composition and EC risk. Sensitivity analyses were conducted to ensure the robustness of the findings.

Our study identified several microbial taxa linked to EC risk. In Europeans, genera such as Marvinbryantia, RuminococcaceaeUCG014, and Dorea exhibited protective effects, while family Erysipelotrichaceae (OR:1.224) and FamilyXI (OR:1.090) were significantly correlated with high EC risk. In East Asians, genera Lachnospira (OR:3.561) and family Bifidobacteriaceae (OR:1.715) were found associated with EC risk. Genera Lachnoclostridium and ErysipelotrichaceaeUCG003, family Coriobacteriaceae positively served as protective factors. Sensitivity analyses confirmed the reliability of our results, and there was no evidence of pleiotropy or heterogeneity. Our analysis identified several microbial taxa associated with EC risk. In Europeans, genera such as Marvinbryantia, Ruminococcaceae UCG014, and Dorea demonstrated protective effects, while the families Erysipelotrichaceae (OR: 1.224) and FamilyXI (OR: 1.090) were significantly associated with increased EC risk. In East Asians, the genus Lachnospira (OR: 3.561) and the family Bifidobacteriaceae (OR: 1.715) were linked to higher EC risk, whereas the genera Lachnoclostridium and Erysipelotrichaceae UCG003 and the family Coriobacteriaceae were identified as protective factors. Sensitivity analyses confirmed the reliability of these results, with no evidence of pleiotropy or heterogeneity.

This study highlights a relationship between gut microbiota and EC, emphasizing the potential of gut microbiota as therapeutic targets and biomarkers for assessing EC prognosis and treatment efficacy. These findings provide novel insights into the role of gut microbiota in the development and progression of EC.

The world's population requires adequate food supply, satisfying specific nutrient requirements to meet dietary recommendations, promote nutrition security and sustain health, while stimulating agriculture biodiversity. This study assessed the potential of buckwheat and fava bean to diversify the source of dietary nutrients.

Twenty healthy volunteers (n = 6 men, n = 14 women; 42.08 ± 12.12 years; body mass index 24.72 ± 4.69 kg/m2) were recruited in a randomised controlled crossover study consisting of two seven-day intervention periods, buckwheat- and fava bean-based diets were provided to meet individual volunteers resting metabolic rate requirements. The study assessed subjective hunger and the impact of the diets on the gut microbiota composition and the plasma profiles of lipids, glucose, insulin, urea and homocysteine. Plasma, urine and faecal metabolites were also measured before and after consumption of each diet using targeted metabolomics (LC- and GC-MS).

Both intervention diets were as satiating as the volunteers' habitual diets (p = 0.234). The fava bean diet significantly reduced fasted plasma glucose and insulin and increased plasma homocysteine (p < 0.05). Buckwheat diet decreased plasma homocysteine (p < 0.01) and increased plasma, urine and faecal concentrations of salicylic acid and 2,3-dihydroxybenzoic acid. Both diets significantly increased plasma non-esterified fatty acids values, reduced plasma urea and faecal deoxycholic acid concentrations (p < 0.05). The fava bean diet provided significantly higher amounts of dietary fibre (both in comparison with habitual and buckwheat diet) significantly increasing the urine indole-3-propionic acid concentration (p < 0.01) (Day 0 vs. Day 7) and the faecal, plasma and urine indole-3-propionic acid concentrations (p < 0.01) (on Day 7 buckwheat vs. Day 7 fava bean diet). Furthermore, the fava bean diet promoted the growth of the gut bacterium Coprococcus eutactus (p < 0.05).

Buckwheat and fava bean contribute in a sustainable way to meet dietary recommendations and to promote dietary diversification. Diets rich in buckwheat and fava bean were found to be satiating and to beneficially modulate several biomarkers, bacteria and metabolites which are correlated with prevention of metabolic disorders such as cardiovascular disease and type 2 diabetes.

Recent studies from our laboratory demonstrated that the gut microbial community represents a thermogenic biomass, as cecectomy causes an ∼8% decrease in total energy expenditure (EE) via suppression of anaerobic EE. The composition of the microbial community also dictates the EE of the microbial biomass as treatment with the antipsychotic, risperidone, suppresses anaerobic EE in a microbiome-dependent manner. Finally, we have determined that a specialized metabolite produced by Limosilactobacillus reuteri, reutericyclin (RTC), opposes the weight-gain effects of risperidone. In the present study, we performed comprehensive evaluations of energy balance in female C57BL/6J mice treated with risperidone, RTC, or both, to identify mechanisms by which RTC affects energy balance to mitigate risperidone-induced weight gain. We observed that risperidone suppressed anaerobic EE, and that RTC coadministration ameliorated the anaerobic EE suppression and weight gain induced by risperidone. Because anaerobic EE is dependent on the gut microbiota, we performed 16S and whole genome shotgun sequencing on stool and cecal samples following whole animal calorimetry. Risperidone and RTC treatments reciprocally modified the relative abundance of taxa known to participate in fermentation, especially for the production of short-chain fatty acids, which have been correlated with health and leanness in both humans and mice. Together, our data demonstrate that treatment with RTC positively modulates anaerobic EE, possibly by enhancing fermentation of the gut microbial community, and may represent a novel therapeutic in the treatment of obesity.NEW & NOTEWORTHY The gut microbial community represents a thermogenic biomass. The composition of the microbial community dictates energy expenditure of the microbial biomass and is altered by xenobiotics and bacterial metabolites. This study demonstrates that treatment with reutericyclin positively modulates anaerobic energy expenditure and may represent a novel therapeutic in the treatment of obesity.

In the early days, maternal immunoglobulins are essential for sustaining a balanced gut environment by influencing the interaction between the host and the microbiome. The successional establishment of the pioneer strains is an interesting topic of research where maternal immunoglobulins appear to be important. This proof-of-concept study explored the binding pattern of IgA1, IgA2, IgM, and IgG classes to a commensal bacterial in human colostrum and the stool of breastfed neonates. We used flow cytometry coupled with 16S rRNA gene sequencing in human colostrum and neonatal feces samples to characterize this Ig-microbiota association. We observed that in human colostrum samples, IgA2 and IgM bind alfa and beta Proteobacteria, which can potentially stimulate neonatal immune system development in the gut. Other immunoglobulins like IgG predominantly bind facultative anaerobes belonging to the Firmicutes phylum, reported as part of human milk microbiota and pioneer colonizers of the neonatal gut. Maternal immunoglobulins also bind a wide diversity of bacteria in the neonatal stool. For instance, IgA2 and IgM bound more members of the phylum Bacteroidetes in comparison to IgG, these Bacteroidetes and some firmicutes have been reported as late colonizers of the neonatal gut, and their presence is important due to their ability to produce important short chain fatty acids like propionate and butyrate. Our results support the current view that microbial and immunoglobulin transference is crucial for developing the neonate's immune system and individual gut microbiota.

This study investigated the effects of dietary short-chain fatty acid (SCFA) supplementation, on growth performance, metabolism, and antioxidant status of European seabass juveniles. Six isoproteic (43 % crude protein) and isolipidic (18 % crude lipid) diets were formulated to include 0.25 and 0.50 % Sodium acetate (SA), Sodium propionate (SP), or Sodium butyrate (SB). A diet without SCFA supplementation was used as a control. The diets were fed to triplicate groups of European seabass juveniles (initial body weight of 15 g) for 56 days. The supplementation of SCFA in the diet had no impact on the growth, feed utilization, or body composition of seabass. In the intestine, gene expression of pyruvate kinase (pk) and glucokinase (gk), phosphoenolpyruvate carboxykinase (pepck), glucose facilitative carrier type 2 (glut2), and citrate synthase (cs) was lower in fish fed the SP0.50 diet than in the other groups. Moreover, fatty acid synthase (fas) gene expression was lower in fish fed the SA0.25, SA0.50, and SB0.25 diets than in the other groups. Further, catalase (CAT) and glutathione reductase (GR) activity and lipid peroxidation (LPO) levels showed no differences between groups. In contrast, glutathione peroxidase (GPX) activity was higher in fish fed the SP0.50 diet. In the liver, GR activity and LPO levels showed no differences between groups. In contrast, CAT activity was lower in all dietary treatments than in control, and GPX and G6PDH activity was lower in fish fed with the SB (0.25 and 0.50 %) diet than in the other diets. Overall, SCFA supplementation did not affect growth performance and feed utilization and only had minor effects on metabolism and antioxidant defense mechanisms.

Gut microbiota has been gaining increasing attention and its important role in the maintenance of a general good health condition is already established. The potential of gut microbiota modulation through diet is an important research focus to be considered. Lipids, as omega-3 fatty acids, are well known for their beneficial role on organs and corresponding diseases. However, their impact on gut microbiota is still poorly defined, and studies on the role of other polyunsaturated fatty acids, such as conjugated linoleic and linolenic acids, are even scarcer.

By using an in vitro human fermentation model, we assessed the effect of omega-3, CLA isomers, and punicic acid on microbiota modulation.

Fish oil, Omega-3, and CLA samples positively impact Akkermansia spp. and Bifidobacterium spp. growth. Moreover, all the samples supported Roseburia spp. growth after 24 h of fermentation and, importantly, they were able to maintain the Firmicutes: Bacteroidetes ratio near 1. All the bioactive fatty acid samples, except Pomegranate oil, were able to significantly increase butyrate levels compared to those found in the positive control (FOS) sample. Moreover, Fish oil and Omega-3 samples were able to increase the concentration of GABA, alanine, tyrosine, phenylalanine, isoleucine, and leucine between 12 and 24 h of fermentation.

The impact of the assessed polyunsaturated fatty acids in gut microbiota has been observed in its impact on key bacteria (Akkermansia, Bifidobacterium, and Roseburia) as well as their metabolic byproducts, including butyrate and amino acids, which could potentially play a role in modulating the gut-brain axis.

Astragalus membranaceus and Codonopsis pilosula are traditional Chinese medicines known for their tonifying effects, which are linked to the metabolism of their polysaccharide components in the gut. However, the role of gut microbiota in the degradation of these polysaccharides to butyric acid remains unclear. This study aims to investigate the in vitro degradation of polysaccharides from Astragalus membranaceus and Codonopsis pilosula by healthy mice fecal microbiota, focusing on butyric acid production and the associated microbial gene expression. We conducted an in vitro analysis of the degradation of homogeneous polysaccharides. from Astragalus membranaceus and Codonopsis pilosula using fecal microbiota cultures derived from healthy mice. The fecal microbiota was cultured with the polysaccharides for 48 hours, after which the degradation liquid was collected for butyric acid quantification and metatranscriptome analysis of the microbiota. The degradation of Astragalus membranaceus polysaccharide resulted in a significant increase in butyric acid levels compared to those produced from Codonopsis pilosula polysaccharide or fructooligosaccharide (control). Differential gene expression analysis indicated an upregulation of carbohydrate-active enzymes and genes associated with butyrate production during the degradation of Astragalus membranaceus polysaccharides. Additionally, the findings suggested that synergistic interactions between polysaccharide-degrading and butyrate-producing bacteria play a crucial role in the microbiota's response to specific polysaccharides. This study highlights the potential of Astragalus polysaccharides to enhance butyric acid production through specific gut microbiota interactions, suggesting their beneficial effects on gut health and metabolism. Further research may provide insights into the therapeutic applications of these traditional medicines in modulating gut microbiota and improving health outcomes.IMPORTANCEThis study significantly advances our understanding of the role of gut microbiota in the metabolism of traditional Chinese medicinal polysaccharides, specifically those from Astragalus membranaceus and Codonopsis pilosula. By demonstrating that Astragalus membranaceus polysaccharide enhances butyric acid production more effectively than Codonopsis pilosula polysaccharide or fructooligosaccharides, the research highlights the potential of these natural compounds in modulating gut health. The identification of upregulated carbohydrate-active enzymes and butyrate production genes provides valuable insights into the microbial mechanisms underlying polysaccharide degradation. This work not only contributes to the field of microbiome research but also supports the development of functional foods and therapeutics aimed at enhancing gut health through targeted polysaccharide consumption.

Vancomycin-resistant enterococci (VRE) often originate from the gastrointestinal tract, where their proliferation precedes dissemination into the bloodstream, and can lead to systemic infection. Uncovering the actors and mechanisms reducing the intestinal colonisation by VRE is essential to control infection. We aimed to identify commensal bacteria that interfere with VRE gut colonisation or act as an ecological barrier.

We performed a 3-week longitudinal analysis of the gut microbiota composition and VRE carriage levels during microbiota recovery in mice colonised with VRE after antibiotic-induced dysbiosis. By combining biological data and mathematical modelling, we identified 15 molecular species (OTUs) that negatively correlated with VRE overgrowth. Six strains representative of these OTUs were collected, cultivated and used in mixture with a seventh strain (Mix7) in two different mouse lines challenged with VRE. Of the seven strains, three belonged to Lachnospiraceae, one to Muribaculaceae, one to Ruminococcaceae and two to Lactobacillaceae. We found that Mix7 led to a better recovery of the gut microbiota composition and reduced VRE carriage. Differences in the effect of Mix7 were observed between responder and non-responder mice. These differences were associated with variations in the composition of the initial microbiota and during recovery and represent potential biomarkers for predicting response to Mix7. In a mouse model of alternative stable state of dysbiosis, response to Mix7 was associated with higher concentrations of short-chain fatty acids (acetate, propionate, butyrate) and a range of metabolites including bile acids, reflecting the recovery of the microbiota back to initial state. Furthermore, Muribaculum intestinale strain was required to obtain the Mix7 effect on VRE reduction in vivo, but the presence of at least one of the other six strains was needed. None of the supernatant of the seven strains, alone or in combination, inhibited VRE growth in vitro. Interestingly, five strains belong to species shared among humans and mice, and the other two have human functional equivalents.

An innovative approach based on mathematical modelling of the microbiota composition permitted to identify a mixture of commensal bacterial strains, which improves the ecological barrier effect against VRE. The mechanisms are dependent on the recovery and initial composition of the microbiota. Ultimately, this work will enable a move towards a personalised medicine by targeting predisposed patients presenting a risk of infection, such as neutropenic or bone-marrow transplant patients, and likely to respond to supplementation with commensal strains, providing new live biotherapeutic products and biomarkers to predict response to supplementation. Video Abstract.

The gut microbiome refers to the collective genomes of the approximately 1,000-1,150 microbial species found in the human gut, called the gut microbiota. Changing the gut microbiota composition has been shown to affect cardiovascular health significantly. Numerous studies have demonstrated the part that gut microbiota and its metabolites play in the development and course of several illnesses, including colon cancer, heart failure, stroke, hypertension, and inflammatory bowel disease. With cardiovascular diseases responsible for more than 31% of all fatalities globally, conditions like hypertension, atherosclerosis, and heart failure are serious global health issues. Developing preventive measures to fight cardiovascular diseases requires understanding how the gut microbiota interacts with the cardiovascular system. Understanding the distinctive gut microbiota linked to cardiovascular diseases has been made possible by microbial sequencing analysis. The gut microbiota and cardiovascular diseases are closely related, and more profound knowledge of this association may result in treatment strategies and broad guidelines for enhancing cardiovascular health through gut microbiome modification. This review summarizes the role of gut microbiota in cardiovascular diseases, highlighting their influence on disease progression and potential therapeutic implications.

Bone loss induced by mechanical unloading is a critical concern in aerospace medicine and for patients subjected to prolonged bed rest. In this study, we investigated the effects of mechanical unloading on the gut microbiota and short-chain fatty acid (SCFA) metabolism, as well as the potential role of butyrate in mitigating bone loss. Through a combination of a hindlimb unloading model, microbiological assessments, and metabolic profiling, we demonstrated that mechanical unloading significantly reduced gut microbiota diversity, altered the Firmicutes-to-Bacteroidetes ratio, and decreased total SCFA levels. Furthermore, butyrate supplementation mitigated the adverse effects of mechanical unloading on the bone microstructure by increasing ELK1 protein expression through HDAC2 inhibition, thus promoting osteoblast differentiation and bone formation. These findings highlight the intricate relationships among gut microbiota alterations, SCFA metabolism, and bone health during mechanical unloading, suggesting that butyrate may be a potential therapeutic agent to counteract bone loss in microgravity environments.

To assess the effects and underlying mechanisms of Coptis chinensis, a traditional Chinese herb known for its antiallergic properties, crude polysaccharides (CP1) were extracted via water extraction, and homopolysaccharides were purified by column chromatography. This study analyzed the sugar and protein content, molecular weight distribution, monosaccharide composition, and functional groups of C. chinensis polysaccharides and evaluated their antiallergic effects in mice sensitized to ovalbumin (OVA). The results showed that the purified homopolysaccharide (CP2-3-1, 138.78 kDa, primarily composed of glucose) was more effective than CP1 in alleviating allergic symptoms. CP2-3-1 treatment led to improvements in anaphylactic scores, diarrhea rates, rectal temperatures, jejunum structure, and levels of immunoglobulin E (IgE), mouse mast cell protease-1 (mMcep1), and interleukin-4 (IL-4) antibodies in mouse serum, which were similar to those in the phosphate-buffered saline (PBS) control group. In addition, CP2-3-1 treatment significantly increased the richness and diversity of the gut microbiota in OVA-sensitized mice, restoring core microbiota to near-PBS levels, including key phyla (Firmicutes and Bacteroidetes) and important families (Lachnospiraceae, Lactobacillaceae, Rikenellaceae, and Muribaculaceae). This research confirms the antiallergic effects of polysaccharides from C. chinensis and highlights the potential for developing new food allergy therapies based on C. chinensis homopolysaccharides.

The intestinal barrier is a critical defense against external pathogens and plays a central role in immune regulation and nutrient absorption. Oxidative stress and chronic inflammation in high-altitude environments can exacerbate the damage to the intestinal barrier in Baimei ternary pigs. Anthocyanin extract of Lycium ruthenicum Murray (AEL), has garnered widespread attention due to its rich anthocyanin flavonoid content, which exhibits antioxidant and anti-inflammatory properties. These properties help alleviate inflammation and oxidative stress, thereby enhancing gut function in animals. Based on this, the study employed Bamei ternary pigs and supplemented their basic diet with varying concentrations of AEL to investigate its impact on gut barrier function. The results demonstrated that AEL inhibited key factors of the intestinal Toll-like receptor pathway, including Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated protein 6 (TRAF6), and nuclear factor kappa B (NF-κB), affecting gene transcription and protein expression levels. This led to a reduction in pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), an increase in anti-inflammatory IL-10 production, and improved antioxidant capacity by enhancing total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity, while decreasing malondialdehyde (MDA) production. Additionally, AEL improved intestinal morphology and facilitated the transcription and expression of tight junction proteins, including zonula occludens-1 (ZO-1), claudin-1 (CLDN-1), and occludin (OCLN). AEL also elevated the transcription levels of mucin 1 (MUC1) and mucin 2 (MUC2), as well as the secretion levels of polymeric immunoglobulin receptor (pIgR) and secretory immunoglobulin A (SIgA), while increased the number of intestinal goblet cells. Furthermore, dietary supplementation with AEL altered the structure of the intestinal microbiota, enhancing the abundance of beneficial bacterial genera such as Verrucomicrobiaceae, Rikenellaceae, Butyricicoccaceae, UCG-005、Rikenellaceae_RC9_gut_group、norank_f_Ruminococcaceae、Eubacterium_oxidoreducens_group, thereby promoting the production of intestinal short-chain fatty acids (SCFAs). In conclusion, AEL inhibits the Toll-like receptor pathway, reduces the production of inflammatory factors, enhances antioxidant levels, improves intestinal morphology and microbiota structure,, thereby reinforcing intestinal barrier function.

Obesity, characterized by excessive fat accumulation, stems from an imbalance between energy intake and expenditure, with the gut microbiota playing a crucial role. This review highlights how gut microbiota influences metabolic pathways, inflammation, and adipose tissue regulation in obesity. Specific bacteria and metabolites, such as lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs), modulate gut permeability, inflammation, and energy harvest, impacting obesity development. Certain gut bacteria, including Clostridium XIVb, Dorea spp., Enterobacter cloacae, and Collinsella aerofaciens, promote obesity by increasing energy harvest, gut permeability, and inflammatory response through LPS translocation into the bloodstream. Conversely, beneficial bacteria like Akkermansia muciniphila, Lactobacillus spp., and Bifidobacterium spp. enhance gut barrier integrity, regulate SCFA production, and modulate fasting-induced adipose factor, which collectively support metabolic health by reducing fat storage and inflammation. Metabolites such as SCFAs (acetate, propionate, and butyrate) interact with G-protein coupled receptors to regulate lipid metabolism and promote the browning of white adipose tissue (WAT), thus enhancing thermogenesis and energy expenditure. However, LPS contributes to insulin resistance and fat accumulation, highlighting the dual roles of these microbial metabolites in both supporting and disrupting metabolic function. Therapeutic interventions targeting gut microbiota, such as promoting WAT browning and activating brown adipose tissue (BAT), hold promise for obesity management. However, personalized approaches are necessary due to individual microbiome variability. Further research is essential to translate these insights into microbiota-based clinical therapies.

Obesity is a significant health concern, significantly contributing to increased morbidity and mortality by disrupting multiple physiological systems. It is strongly associated with metabolic dysfunctions, including impaired glycemic homeostasis, compromised intestinal barrier integrity, and gut microbiota imbalances, all exacerbating the risk of chronic diseases. The hydroalcoholic extract of açaí seeds (ASE), rich in phenolic compounds, has demonstrated beneficial effects on obesity and hyperglycemia; however, its impacts on gut health and gut-hypothalamus communication remain unclear. This study aimed to investigate the therapeutic effect of ASE in intestinal and hypothalamic alterations associated with obesity and compare it with Metformin. Male C57BL/6 mice were fed a high-fat or standard diet for 14 weeks. The ASE (300 mg/kg/day) and Metformin (300 mg/kg/day) treatments started in the tenth week until the fourteenth week, totaling four weeks of treatment. Our data show that the treatment with ASE and Metformin reduced body weight, ameliorated lipid profile, hyperglycemia, and plasma hyperleptinemia, and decreased the oxidative damage in the gut by reducing immunostaining of 8-isoprostane and NOX-4 expression, and improved the intestinal parameters and hypothalamic gene expression. Obesity-induced dysbiosis in the HF group was marked by reduced Proteobacteria and elevated LPS plasma levels, which were improved by treatments with ASE and Metformin. These findings suggest that ASE and Metformin are promising strategies to counteract the adverse effects of obesity on intestinal health and gut-hypothalamus communication, though they act through distinct mechanisms. Therefore, we can suggest that ASE is a promising natural product for treating the intestinal alterations associated with obesity.

In recent years, the gut microbiota has been increasingly recognized for its influence on various central nervous system diseases mediated by microglia, yet the underlying mechanisms remain unclear. As key metabolites of the gut microbiota, short-chain fatty acids (SCFAs) have emerged as a focal point in understanding microglia-related interactions. In this review, we further refine the connection between the gut microbiota and microglia by introducing the concept of the "SCFAs-microglia" pathway. We summarize current knowledge on this pathway, recent discoveries regarding its role in neurological diseases, and potential pharmacological strategies targeting it. Finally, we outlined the current challenges and limitations in this field of research. We hope this review provides new insights into the role of the gut microbiota in neuroimmune regulation.

Dietary fiber, especially resistant starch (RS) Type 2 (RS2) found in high-amylose maize starch (HAMS), is vital for gut health and helps prevent colon cancer. In contrast to most nutrients, dietary fiber is not degraded by the intestinal enzymes; it reaches the distal parts of the gut, where it is fermented by the gut microbiota into short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate. SCFAs energize colonocytes, reduce inflammation, and enhance gut immunity. HAMS is absorbed in the colon, where it ferments to create SCFAs that feed good gut flora and have antiinflammatory and antiproliferative effects. RS2 in HAMS modulates gene signaling, activates tumor-suppressor genes like tumor suppressor protein (p53), exhibits antidiabetic, cholesterol-lowering, and antiinflammatory effects. Incorporation of RS2-rich sources enhances gut barriers, decreases colorectal cancer biomarkers, and counteracts the negative impacts of low-fiber Western diets, making HAMS a promising functional food for chronic disease prevention and health promotion.

This study evaluates the efficacy of the postbiotic Probio-Eco in alleviating constipation in humans and mice. A randomized, double-blind, placebo-controlled crossover trial involving 110 adults with chronic constipation (Rome IV criteria) demonstrates that a 3-week Probio-Eco intervention significantly improves constipation symptoms, stool straining, and worry scores. Gut microbiota and metabolomic analyses reveal modulations in specific gut microbiota, succinate, tryptophan derivatives, deoxycholate, propionate, butyrate, and cortisol, correlating with symptom relief. A loperamide-induced mouse model confirms that Probio-Eco and its bioactive components (succinate, 3-indoleacrylic acid, and 5-hydroxytryptophan) alleviate constipation by stimulating mucin-2 secretion, regulating intestinal transport hormones, and promoting anti-inflammatory responses. Multi-omics integration identifies key pathways, including succinate-short-chain fatty acid, tryptophan-5-hydroxytryptophan-serotonin, and tryptophan-3-indoleacrylic acid, driving intestinal homeostasis and motility. These findings highlight the comprehensive efficacy of Probio-Eco and provide robust evidence for its clinical application in constipation management. This study was registered at Chinese Clinical Trial Registry (ChiCTR2100054376).

Growing evidence suggests that inadequate dietary fiber intake, termed the "fiber gap," is linked to disease states through disruption of the gut microbiota. Despite this, our understanding of how various fiber structures influence the microbiota and health is limited by the lack of diverse commercially available fibers. Studies have primarily focused on a limited range of fibers, rather than the diverse array of fibers representative of those commonly found in our diets. In this study, we aimed to investigate how naturally derived fibers impact the human microbiota and their metabolic products. We performed a comprehensive structural characterization and functional evaluation of a unique and highly diverse set of new, highly soluble fibers with varied monosaccharide compositions, glycosidic linkages, and polymer lengths. Using an ex vivo high-throughput human microbiota platform coupled with metabolomic profiling, we demonstrate that these diverse fibers drive distinct and consistent microbial and metabolic profiles across cohorts of donors in a structure-dependent manner. These metabolic effects were accompanied by both general and donor-specific changes in microbial taxa. Finally, we demonstrate that integrating detailed glycomic characterization with microbial and metabolomic data allowed for prediction of functional outcomes driven by a novel material, pineapple pulp fiber. This work highlights the potential for targeted dietary fiber interventions to modulate the microbiota and improve health outcomes, paving the way for the development of new fiber-rich products with specific health benefits.IMPORTANCEFiber deficiency is associated with numerous disease states, many of which are linked to disruption of the gut microbiota. This study encompasses the first systematic and comprehensive characterization of a diverse collection of naturally derived solubilized fibers and their impacts on the microbiota. The results expand our understanding of the beneficial effects of specific carbohydrate structures naturally found in the human diet, highlighting the potential for designing fiber-based health interventions. The high solubility of these fibers increases both the range of products they can be incorporated in as well as their assayability in experiments, enabling a widespread increase in fiber consumption and positive health impacts.

Biodegradable polylactic acid (PLA) plastics have been praised as an effective solution to the global pollution caused by petroleum-based plastics, and their widespread use in food packaging and disposable tableware has resulted in increased oral exposure to PLA microplastics (PLA-MPs). Despite their eco-friendly and biodegradable reputation, the in vivo behaviors of PLA-MPs concerning fermentation, carbon cycle, and adverse effects remain unknown. Here, we showed that gut microbiota from the colon can effectively degrade the PLA-MPs by secreting esterase FrsA, whereas esterase FrsA-producing bacteria were identified to dominate this behavior in male C57BL/6 mice. Using isotope tracing and multiomics techniques, we uncovered that 13C-labeled PLA-MPs were incorporated into the carbon cycle of gut microbiota as a carbon source. Meanwhile, these degraded PLA-MPs fragments entered the succinate pathway of the tricarboxylic acid cycle within gut epithelial cells. These processes altered the metabolic phenotype of the gut, resulting in the decreased linear short-chain fatty acids that are primary energy sources of the gut epithelium. Furthermore, we found that exposure of PLA-MPs significantly reduced the appetite and body weight of mice. Our findings present an overall process of biodegradable plastics within hosts, with the focus on the entire double carbon cycle of PLA-MPs in the gut, which offers indispensable insights into the potential impact of exposure to PLA-MPs.

Short-chain fatty acids (SCFAs) are a group of organic compounds produced by the fermentation of dietary fibre by the human gut microbiota. They play diverse roles in different physiological processes of the host with implications for human health and disease. This Review provides an overview of the complex microbial metabolism underlying SCFA formation, considering microbial interactions and modulating factors of the gut environment. We explore the multifaceted mechanistic interactions between SCFAs and the host, with a particular focus on the local actions of SCFAs in the gut and their complex interactions with the immune system. We also discuss how these actions influence intestinal and extraintestinal diseases and emerging therapeutic strategies using SCFAs.