Metagenomic analysis of colonic tissue and stool microbiome in patients with colorectal cancer in a South Asian population.

BACKGROUND: The gut microbiome is thought to play an important role in the development of colorectal cancer (CRC). However, as the gut microbiome varies widely based on diet, we sought to investigate the gut microbiome changes in patients with CRC in a South Asian population. METHODS: The gut microbiome was assessed by 16s metagenomic sequencing targeting the V4 hypervariable region of the bacterial 16S rRNA in stool samples (n = 112) and colonic tissue (n = 36) in 112 individuals. The cohort comprised of individuals with CRC (n = 24), premalignant lesions (n = 10), healthy individuals (n = 50) and in those with diabetes (n = 28). RESULTS: Overall, the relative abundances of genus Fusobacterium (p < 0.001), Acinetobacter (p < 0.001), Escherichia-Shigella (p < 0.05) were significantly higher in gut tissue, while Romboutsia (p < 0.01) and Prevotella (p < 0.05) were significantly higher in stool samples. Bacteroides and Fusobacterium were the most abundant genera found in stool samples in patients with CRC. Patients with pre-malignant lesions had significantly high abundances of Christensenellaceae, Enterobacteriaceae, Mollicutes and Ruminococcaceae (p < 0.001) compared to patients with CRC, and healthy individuals. Romboutsia was significantly more abundant (p < 0.01) in stool samples in healthy individuals compared to those with CRC and diabetes. CONCLUSION: Despite marked differences in the Sri Lankan diet compared to the typical Western diet, Bacteroides and Fusobacterium species were the most abundant in those with CRC, with Prevotella species, being most abundant in many individuals. We believe these results pave the way for possible dietary interventions for prevention of CRC in the South Asian population.

Anastomotic leak occurs independently from microbiota shifts associated with surgical bowel preparation.

Following bowel surgery, infectious complications, including anastomotic leak (AL), remain major sources of morbidity and mortality. Bowel preparation is often administered with the assumption that gut decontamination reduces post-surgical complications. In this study, we tested this hypothesis using a murine model of colon surgery. The mice were fed either regular chow or a high-fat, high-sugar Western diet. The day before surgery, the mice received one of four interventions: water (control), mechanical bowel preparation (MBP), oral antibiotics (OA), or both MBP and OA. We found no differences in the rates of AL among the experimental groups, and diet did not appear to affect the outcomes. Exploratory analyses showed changes in the gut microbiome consistent with the different treatments, but investigations of fecal short-chain fatty acids and RNA sequencing of colonic tissue did not reveal specific effects of the treatments or the presence of AL. However, we did identify bacterial genera that may be causally associated with AL and developed a predictive index from stool samples as a marker for the presence of AL. Future research is needed to identify and validate a microbial predictive tool and to uncover the microbial-driven mechanisms that lead to AL.

FMT rescues mice from DSS-induced colitis in a STING-dependent manner.

Fecal microbiota transplantation (FMT) is currently a promising therapy for inflammatory bowel disease (IBD). However, clinical studies have shown that there is an obvious individual difference in the efficacy of FMT. Therefore, it is a pressing issue to identify the factors that influence the efficacy of FMT and find ways to screen the most suitable patients for this therapy. In this work, we targeted the stimulator of interferon genes (STING), a DNA-sensing protein that regulates host-defense. By comparing the differential efficacy of FMT in mice with different expression level of STING, it is revealed that FMT therapy provides treatment for DSS-induced colitis in a STING-dependent manner. Mechanistically, FMT exerts a regulatory effect on the differentiation of intestinal Th17 cells and macrophages, splenic Th1 and Th2 cells, as well as Th1 cells of the mesenteric lymph nodes via STING, down-regulating the colonic M1/M2 and splenic Th1/Th2 cell ratios, thereby improving the imbalanced immune homeostasis in the inflamed intestine. Meanwhile, based on the 16SrDNA sequencing of mice fecal samples, STING was found to facilitate the donor strain colonization in recipients' gut, mainly Lactobacillales, thereby reshaping the gut microbiota disturbed by colitis. Consequently, we proposed that STING, as a key target of FMT therapy, is potentially a biomarker for screening the most suitable individuals for FMT to optimize treatment regimens and enhance clinical benefit.

Rosa roxburghii Tratt (Cili) has a more effective capacity in alleviating DSS-induced colitis compared to Vitamin C through B cell receptor pathway.

Rosa roxburghii Tratt (RRT), a traditional Chinese plant known as the 'King of Vitamin C (VitC; ascorbic acid, AsA)', contains a wealth of nutrients and functional components, including polysaccharides, organic acids, flavonoids, triterpenes, and high superoxide dismutase (SOD) activity. The various functional components of RRT suggest that it may theoretically have a stronger potential for alleviating colitis compared to VitC. This study aims to verify whether RRT has a stronger ability to alleviate colitis than equimolar doses of VitC and to explore the mechanisms underlying this improvement. Results showed that RRT significantly mitigated body weight loss, intestinal damage, elevated inflammation levels, and compromised barriers in mice induced by Dextran sulfate sodium (DSS). Additionally, RRT enhanced the diversity and composition of intestinal microbiota in these DSS-induced mice. Colon RNA sequencing analysis revealed that compared to VitC, RRT further downregulated multiple immune-related signaling pathways, particularly the B cell receptor (BCR) pathway, which is centered around genes like Btk and its downstream PI3K-AKT, NF-κB, and MAPK signaling pathways. Correlation analysis between microbiota and genes demonstrated a significant relationship between the taxa improved by RRT and the key genes in the BCR and its downstream signaling pathways. Overall, RRT exhibited superior capabilities in alleviating DSS-induced colitis compared to VitC by decreasing intestinal inflammation and modulating BCR and its downstream signaling pathways, potentially regulated by the improved intestinal microbiota.

Bacteroides salyersiae Is a Candidate Probiotic Species with Potential Anti-Colitis Properties in the Human Colon: First Evidence from an In Vivo Mouse Model.

Previous studies have indicated a critical role of intestinal bacteria in the pathogenesis of ulcerative colitis (UC). B. salyersiae is a commensal species from the human gut microbiota. However, what effect it has on UC development has not been investigated. In the present study, we explored this issue and demonstrated for the first time that oral administration of B. salyersiae CSP6, a bacterium previously isolated from the fecal sample of a healthy individual, protected against dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice. In particular, B. salyersiae CSP6 improved mucosal damage and attenuated gut dysbiosis in the colon of DSS-fed mice. Specifically, B. salyersiae CSP6 decreased the population of pathogenic Escherichia-Shigella spp. and increased the abundance of probiotic Dubosiella spp. and Bifidobacterium pseudolongum. Additionally, by reshaping the colonic microbiota, B. salyersiae CSP6 remarkably increased the fecal concentrations of equol, 8-deoxylactucin, and tiglic acid, three beneficial metabolites that have been well documented to exert strong anti-inflammatory effects. Altogether, our study provides novel evidence that B. salyersiae is a candidate probiotic species with potential anti-colitis properties in the human colon, which has applications for the development of next-generation probiotics.

The DAV132 colon-targeted adsorbent does not interfere with plasma concentrations of antibiotics but prevents antibiotic-related dysbiosis: a randomized phase I trial in healthy volunteers.

The deleterious impact of antibiotics (ATB) on the microbiome negatively influences immune checkpoint inhibitors (ICI) response in patients with cancer. We conducted a randomized phase I study (EudraCT:2019-A00240-57) with 148 healthy volunteers (HV) to test two doses of DAV132, a colon-targeted adsorbent, alongside intravenous ceftazidime-avibactam (CZA), piperacillin-tazobactam (PTZ) or ceftriaxone (CRO) and a group without ATB. The primary objective of the study was to assess the effect of DAV132 on ATB plasma concentrations and both doses of DAV132 did not alter ATB levels. Secondary objectives included safety, darkening of the feces, and fecal ATB concentrations. DAV132 was well tolerated, with no severe toxicity and similar darkening at both DAV132 doses. DAV132 led to significant decrease in CZA or PTZ feces concentration. When co-administered with CZA or PTZ, DAV132 preserved microbiome diversity, accelerated recovery to baseline composition and protected key commensals. Fecal microbiota transplantation (FMT) in preclinical cancer models in female mice from HV treated with CZA or PTZ alone inhibited anti-PD-1 response, while transplanted samples from HV treated with ATB + DAV132 circumvented resistance to anti-PD-1. This effect was linked to activated CD8+ T cell populations in the tumor microenvironment. DAV132 represents a promising strategy for overcoming ATB-related dysbiosis and further studies are warranted to evaluate its efficacy in cancer patients.

Caffeic Acid Phenethyl Ester Administration Reduces Enterotoxigenic Bacteroides fragilis-Induced Colitis and Tumorigenesis.

The human colonic commensal enterotoxigenic Bacteroides fragilis (ETBF) is associated with chronic colitis and colon cancer. ETBF colonization induces colitis via the Bacteroides fragilis toxin (BFT). BFT secreted by ETBF cause colon inflammation via E-cadherin cleavage/NF-κB signaling. ETBF promotes colon tumorigenesis via interleukin 17A (IL-17A)/CXCL-dependent inflammation, but its bioactive therapeutics in ETBF-promoted tumorigenesis remain unexplored. In the current study, we investigated the caffeic acid phenethyl ester (CAPE) in the murine model of ETBF colitis and tumorigenesis. In this study, we observed that CAPE treatment mitigated inflammation induced by ETBF in mice. Additionally, our findings indicate that CAPE treatment offers protective effects against ETBF-enhanced colon tumorigenesis in a mouse model of colitis-associated colon cancer induced by azoxymethane (AOM) and dextran sulfate sodium. Notably, the decrease in colon tumorigenesis following CAPE administration correlates with a reduction in the expression of IL-17A and CXCL1 in the gastrointestinal tract. The molecular mechanism for CAPE-induced protection against ETBF-mediated tumorigenesis is mediated by IL-17A/CXCL1, and by NF-κB activity in intestinal epithelial cells. Our findings indicate that CAPE may serve as a preventive agent against the development of ETBF-induced colitis and colorectal cancer (CRC).

Effects of inactivated Lactobacillus rhamnosus on growth performance, serum indicators, and colonic microbiota and metabolism of weaned piglets.

BACKGROUND: To assess the effects of inactivated Lactobacillus rhamnosus (ILR) on growth performance, serum biochemical indices, colonic microbiota, and metabolomics in weaned piglets, 120 piglets were randomly divided into five groups. Samples in the control group were fed a basal diet, while the experimental ILR1, ILR2, ILR3, and ILR4 groups were fed basal diets supplemented with 0.1%, 0.2%, 0.3%, and 0.4% ILR, respectively. The prefeeding period lasted for 5 days and was followed by a formal period of 28 days. RESULTS: Compared to the control, the average daily gain increased by 4.38%, 7.98%, 19.32%, and 18.80% for ILR1, ILR2, ILR3, and ILR4, respectively, and the ratio of feed to gain decreased by 0.63%, 3.80%, 12.66%, and 10.76%, respectively. Serum IgA, IgG, IgM, total antioxidant capacity, and glutathione peroxidase levels increased significantly in weaned piglets in the treatment groups. Addition of 0.3% ILR significantly increased the Shannon and Simpson indices of the colonic microbiota in weaned piglets and altered the microbiota composition. Changes in metabolic profiles were observed and were primarily related to the urea cycle, amino acid metabolism, and lipid metabolism. CONCLUSION: ILR improved growth performance and serum immunological and biochemical indices and optimized the colonic microbiota structure and metabolism of weaned piglets.

Antibiotics damage the colonic mucus barrier in a microbiota-independent manner.

Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs). IBDs are characterized by a damaged mucus layer, which does not separate the intestinal epithelium from the microbiota. Here, we hypothesized that antibiotics affect the integrity of the mucus barrier, which allows bacterial penetrance and predisposes to intestinal inflammation. We found that antibiotic treatment led to breakdown of the colonic mucus barrier and penetration of bacteria into the mucus layer. Using fecal microbiota transplant, RNA sequencing followed by machine learning, ex vivo mucus secretion measurements, and antibiotic treatment of germ-free mice, we determined that antibiotics induce endoplasmic reticulum stress in the colon that inhibits colonic mucus secretion in a microbiota-independent manner. This antibiotic-induced mucus secretion flaw led to penetration of bacteria into the colonic mucus layer, translocation of microbial antigens into circulation, and exacerbation of ulcerations in a mouse model of IBD. Thus, antibiotic use might predispose to intestinal inflammation by impeding mucus production.

Gastrointestinal digestion of yerba mate, rosemary and green tea extracts and their subsequent colonic fermentation by human, pig or rat inocula.

Polyphenolic compounds are common constituents of human and animal diets and undergo extensive metabolism by the gut microbiota before entering circulation. In order to compare the transformations of polyphenols from yerba mate, rosemary, and green tea extracts in the gastrointestinal tract, simulated gastrointestinal digestion coupled with colonic fermentation were used. For enhancing the comparative character of the investigation, colonic fermentation was performed with human, pig and rat intestinal microbiota. Chemical analysis was performed using a HPLC system coupled to a diode-array detector and mass spectrometer. Gastrointestinal digestion diminished the total amount of phenolics in the rosemary and green tea extracts by 27.5 and 59.2 %, respectively. These reductions occurred mainly at the expense of the major constituents of these extracts, namely rosmarinic acid (-45.7 %) and epigalocatechin gallate (-60.6 %). The yerba mate extract was practically not affected in terms of total phenolics, but several conversions and isomerizations occurred (e.g., 30 % of trans-3-O-caffeoylquinic acid was converted into the cis form). The polyphenolics of the yerba mate extract were also the least decomposed by the microbiota of all three species, especially in the case of the human one (-10.8 %). In contrast, the human microbiota transformed the polyphenolics of the rosemary and green extracts by 95.9 and 88.2 %, respectively. The yerba mate-extract had its contents in cis 3-O-caffeoylquinic acid diminished by 78 % by the human microbiota relative to the gastrointestinal digestion, but the content of 5-O-caffeoylquinic acid (also a chlorogenic acid), was increased by 22.2 %. The latter phenomenon did not occur with the rat and pig microbiota. The pronounced interspecies differences indicate the need for considerable caution when translating the results of experiments on the effects of polyphenolics performed in rats, or even pigs, to humans.

Cassava (Manihot esculenta) Brazilian cultivars have different chemical compositions, present prebiotic potential, and beneficial effects on the colonic microbiota of celiac individuals.

The purpose of this study was to investigate the potential prebiotic properties of cassava cultivars from Northeast [Doce mel and Ourinho (OUR)] and South [Baiana, and IPR-Upira (UPI)] of Brazil in in vitro fermentation systems. The cultivars were evaluated for their chemical composition, and, then, two cultivars were selected (OUR and UPI) and subjected to in vitro gastrointestinal digestion to assess the effects on probiotics Lacticaseibacillus casei, Lactobacillus acidophilus, and Bifidobacterium animalis growth, metabolic activity, and prebiotic activity scores. Finally, the impact of cassava cultivars on the fecal microbiota of celiac individuals was evaluated using the 16S rRNA gene. Cassava cultivars have variable amounts of fiber, resistant starch, fructooligosaccharides (FOS), organic acids, phenolic compounds, and sugars, with OUR and UPI cultivars standing out. OUR and UPI cultivars contributed to the increase in the proliferation rates of L. casei (0.04-0.19), L. acidophilus (0.34-0.27), and B. animalis (0.10-0.03), resulting in more significant effects than FOS, an established prebiotic compound. Also, the positive scores of prebiotic activities with probiotic strains indicate OUR and UPI's ability to stimulate beneficial bacteria while limiting enteric competitors selectively. In addition, OUR and UPI promoted increased relative abundance of Bifidobacteriaceae, Enterococcaceae, and Lactobacillaceae in the fecal microbiota of celiac individuals while decreased Lachnospirales, Bacteroidales, and Oscillospirales. The results show that cassava cultivars caused beneficial changes in the composition and metabolic activity of the human intestinal microbiota of celiacs. OUR and UPI cultivars from the Northeast and South of Brazil could be considered potential prebiotic ingredients for use in the formulation of functional foods and dietary supplements.

Neohesperidin Attenuates DSS-Induced Ulcerative Colitis by Inhibiting Inflammation, Reducing Intestinal Barrier Damage, and Modulating Intestinal Flora Composition.

Flavonoid natural products are emerging as a promising approach for treating Ulcerative Colitis (UC) due to their natural origin and minimal toxicity. This study investigates the effects of Neohesperidin (NEO), a natural flavonoid, on Dextran Sodium Sulfate (DSS)-induced UC in mice, focusing on the underlying molecular mechanisms. Early intervention with NEO (25 and 50 mg/kg) mitigated colon shortening, restored damaged barrier proteins, and significantly reduced the inflammatory cytokine levels. Moreover, NEO inhibited the MAPK/NF-κB signaling pathway and enhanced the levels of intestinal barrier proteins (Claudin-3 and ZO-1). Additionally, NEO increased beneficial intestinal probiotics (S24-7 and Lactobacillaceae) while reducing harmful bacteria (Erysipelotrichi, Enterobacteriaceae). Fecal microbial transplantation (FMT) results demonstrated that NEO (50 mg/kg) markedly improved UC symptoms. In conclusion, early NEO intervention may alleviate DSS-induced UC by inhibiting inflammatory responses, preserving intestinal barrier integrity and modulating gut microbiota.

Water-soluble garlic polysaccharide (WSGP) improves ulcerative volitis by modulating the intestinal barrier and intestinal flora metabolites.

WSGP has demonstrated significant potential for various bioactive effects. However, limited research has explored their anti-ulcerative colitis (UC) effects and mechanism on the colonic system and gut microbial metabolites. We evaluated the ameliorative effects of WSGP on the UC mice model. Using H&E to assess histological injury of colon morphology, AB-PAS staining to detect mucin secretion from goblet cells and the mucous layer, IF to evaluate the expression of intercellular tight junction proteins, ELISA to measure inflammatory factors, WB analysis to measure protein expression of inflammatory signaling pathways, RT-qPCR to quantify gene transcription of inflammatory factors, and LC-MS to analyze metabolites in mouse cecum contents. WSGP supplementation increased food intake, body weight, and colon length while reducing disease activity and histological scores in colitis-afflicted mice. WSGP mitigated colonic tissue damage and restored intestinal barrier integrity by suppressing NF-κB/STAT3 signaling, thereby decreasing gene transcription, protein expression of proinflammatory factors, and nitric oxide production. Additionally, WSGP improved UC by altering the variety of intestinal microbial metabolites. This study demonstrates that WSGP supplementation attenuates UC mice by suppressing the NF-κB/STAT3 signaling pathway, enhancing mucosal barrier function, reducing pro-inflammatory cytokines, and modulating gut microbial metabolites.

Reconstituting gut microbiota-colonocyte interactions reverses diet-induced cognitive deficits: The beneficial of eucommiae cortex polysaccharides.

Rationale: Consumption of a high-fat diet (HFD) has been implicated in cognitive deficits and gastrointestinal dysfunction in humans, with the gut microbiota emerging as a pivotal mediator of these diet-associated pathologies. The introduction of plant-based polysaccharides into the diet as a therapeutic strategy to alleviate such conditions is gaining attention. Nevertheless, the mechanistic paradigm by which polysaccharides modulate the gut microbiota remains largely undefined. This study investigated the mechanisms of action of Eucommiae cortex polysaccharides (EPs) in mitigating gut dysbiosis and examined their contribution to rectifying diet-related cognitive decline. Methods: Initially, we employed fecal microbiota transplantation (FMT) and gut microbiota depletion to verify the causative role of changes in the gut microbiota induced by HFD in synapse engulfment-dependent cognitive impairments. Subsequently, colonization of the gut of chow-fed mice with Escherichia coli (E. coli) from HFD mice confirmed that inhibition of Proteobacteria by EPs was a necessary prerequisite for alleviating HFD-induced cognitive impairments. Finally, supplementation of HFD mice with butyrate and treatment of EPs mice with GW9662 demonstrated that EPs inhibited the expansion of Proteobacteria in the colon of HFD mice by reshaping the interactions between the gut microbiota and colonocytes. Results: Findings from FMT and antibiotic treatments demonstrated that HFD-induced cognitive impairments pertaining to neuronal spine loss were contingent on gut microbial composition. Association analysis revealed strong associations between bacterial taxa belonging to the phylum Proteobacteria and cognitive performance in mice. Further, introducing E. coli from HFD-fed mice into standard diet-fed mice underscored the integral role of Proteobacteria proliferation in triggering excessive synaptic engulfment-related cognitive deficits in HFD mice. Crucially, EPs effectively counteracted the bloom of Proteobacteria and subsequent neuroinflammatory responses mediated by microglia, essential for cognitive improvement in HFD-fed mice. Mechanistic insights revealed that EPs promoted the production of bacteria-derived butyrate, thereby ameliorating HFD-induced colonic mitochondrial dysfunction and reshaping colonocyte metabolism. This adjustment curtailed the availability of growth substrates for facultative anaerobes, which in turn limited the uncontrolled expansion of Proteobacteria. Conclusions: Our study elucidates that colonocyte metabolic disturbances, which promote Proteobacteria overgrowth, are a likely cause of HFD-induced cognitive deficits. Furthermore, dietary supplementation with EPs can rectify behavioral dysfunctions associated with HFD by modifying gut microbiota-colonocyte interactions. These insights contribute to the broader understanding of the modulatory effects of plant prebiotics on the microbiota-gut-brain axis and suggest a potential therapeutic avenue for diet-associated cognitive dysfunction.

Engineered probiotic ameliorates ulcerative colitis by restoring gut microbiota and redox homeostasis.

Probiotics are potential treatments for ulcerative colitis (UC), but their efficacy is frequently compromised by gastrointestinal conditions that limit adhesion and activity. Here, we use machine learning and bioinformatics to confirm that patients with UC have decreased prevalence of Lactobacillus genus and increased oxidative stress, which correlate with inflammation severity. Accordingly, we developed a probiotic-based therapeutic that synergistically restores intestinal redox and microbiota homeostasis. Lactobacillus casei (Lac) were induced to form a pericellular film, providing a polysaccharide network for spatially confined crystallization of ultrasmall but highly active selenium dots (Se-Lac). Upon oral administration, the selenium dot-embedded pericellular film efficiently enhanced gastric acid resistance and intestinal mucoadhesion of Lac cells. At the lesion site, the selenium dots scavenged reactive oxygen species, while Lac modulated the gut microbiota. In multiple mouse models and non-human primates, this therapeutic effectively relieved inflammation and reduced colonic damage, thus showing promise as a UC treatment.

Gut microbiota dysbiosis deteriorates immunoregulatory effects of tryptophan via colonic indole and LBP/HTR2B-mediated macrophage function.

Tryptophan (Trp) has been shown to regulate immune function by modulating gut serotonin (5-HT) metabolism and signaling. However, the mechanisms underlying the microbial modulation of gut 5-HT signaling in gut inflammation with gut microbiota dysbiosis require further investigation. Here, we investigated the effects of Trp supplementation on the composition and metabolism of the gut microbiome and 5-HT signaling-related gut immune function using a dextran sodium sulfate (DSS)-induced colitis mouse model coupled with antibiotic exposure. The results showed that antibiotic treatment before but not during DSS treatment decreased the immunoregulatory effects of Trp and aggravated gut inflammation and body weight loss in mice. Metagenomic analysis revealed that the fecal microbiota transplantation of Trp-enriched gut microbiota to recipient mice subject to antibiotic pre-exposure and DSS treatment alleviated inflammation by increasing the relative abundances of Lactobacillus and Parabacteroides and the microbial production of indole coupled with the activation of the 5-HT receptor 2B (HTR2B) in the colon. Transcriptomic analysis showed that HTR2B agonist administration strengthened the beneficial effects of Trp in DSS-induced colitis mice with antibiotic exposure by reducing gut lipopolysaccharide-binding protein (LBP) production, IκB-α/nuclear factor-κB signaling, and M1 macrophage polarization. Indole treatment reduced LBP production and M1 macrophage polarization both in mice with DSS-induced colitis and in lipopolysaccharide-treated mouse macrophages; however, the HTR2B antagonist reversed the effects of indole. Our findings provide the basis for developing new dietary and therapeutic interventions to improve gut microbiota dysbiosis-associated inflammatory gut disorders and diseases.

Chronic binge drinking-induced susceptibility to colonic inflammation is microbiome-dependent.

Alterations in intestinal permeability and the gut microbiome caused by alcohol abuse are associated with alcoholic liver disease and with worsening of inflammatory bowel diseases (IBD) symptoms. To resolve the direct effects of chronic ethanol consumption on the colon and its microbiome in the absence of acute or chronic alcohol-induced liver disease, we developed a mouse model of chronic binge drinking that uncovers how alcohol may enhance susceptibility to colitis via the microbiota. Employing daily ethanol gavage, we recapitulate key features of binge ethanol consumption. We found that binge ethanol drinking worsens intestinal infection, colonic injury and inflammation, and this effect persists beyond the drinking period. Using gnotobiotics, we showed that alcohol-driven susceptibility to colitis is microbiota-dependent and transferable to ethanol-naïve mice by microbiome transplantation. Allobaculum spp. expanded in binge drinking mice, and administration of Allobaculum fili was sufficient to enhance colitis in non-drinking mice. Our study provides a model to study binge drinking-microbiota interactions and their effects on host disease and reinforces the pathogenic function of Allobaculum spp. as colitogenic bacteria. Our findings illustrate how chronic binge drinking-induced alterations of the microbiome may affect susceptibility to IBD onset or flares.

Food-breastmilk combinations alter the colonic microbiome of weaning infants: an in silico study.

The introduction of solid foods to infants, also known as weaning, is a critical point for the development of the complex microbial community inhabiting the human colon, impacting host physiology in infancy and later in life. This research investigated in silico the impact of food-breastmilk combinations on growth and metabolite production by colonic microbes of New Zealand weaning infants using the metagenome-scale metabolic model named Microbial Community. Eighty-nine foods were individually combined with breastmilk, and the 12 combinations with the strongest influence on the microbial production of short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) were identified. Fiber-rich and polyphenol-rich foods, like pumpkin and blackcurrant, resulted in the greatest increase in predicted fluxes of total SCFAs and individual fluxes of propionate and acetate when combined, respectively, with breastmilk. Identified foods were further combined with other foods and breastmilk, resulting in 66 multiple food-breastmilk combinations. These combinations altered in silico the impact of individual foods on the microbial production of SCFAs and BCFAs, suggesting that the interaction between the dietary compounds composing a meal is the key factor influencing colonic microbes. Blackcurrant combined with other foods and breastmilk promoted the greatest increase in the production of acetate and total SCFAs, while pork combined with other foods and breastmilk decreased the production of total BCFAs.IMPORTANCELittle is known about the influence of complementary foods on the colonic microbiome of weaning infants. Traditional in vitro and in vivo microbiome methods are limited by their resource-consuming concerns. Modeling approaches represent a promising complementary tool to provide insights into the behavior of microbial communities. This study evaluated how foods combined with other foods and human milk affect the production of short-chain fatty acids and branched-chain fatty acids by colonic microbes of weaning infants using a rapid and inexpensive in silico approach. Foods and food combinations identified here are candidates for future experimental investigations, helping to fill a crucial knowledge gap in infant nutrition.

Lacticaseibacillus casei- and Bifidobacterium breve-fermented red pitaya promotes beneficial microbial proliferation in the colon.

Red pitaya has been demonstrated to strongly inhibit α-glucosidase activity; however, the impact of red pitaya fermentation by probiotic bacteria on α-glucosidase inhibition remains unclear. In this study, six strains of lactic acid bacteria (Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, Lactobacillus bulgaricus, Lacticaseibacillus casei, Lactobacillus acidophilus and Streptococcus thermophilus) and one strain of Bifidobacterium breve were utilized for the fermentation of red pitaya pulp. The α-glucosidase and α-amylase inhibition rates of red pitaya pulp were significantly greater after fermentation by Bifidobacterium breve and Lacticaseibacillus casei than by the other abovementioned strains. The LC group exhibited an α-glucosidase inhibition rate of 99%, with an α-amylase inhibition rate of 89.91%. In contrast, the BB group exhibited an α-glucosidase inhibition rate of 95.28%, accompanied by an α-amylase inhibition rate of 95.28%. Moreover, red pitaya pulp fermented with Bifidobacterium breve and Lacticaseibacillus casei produced a notable quantity of oligosaccharides, which was more than three times greater than that in the other groups. Furthermore, 16S rRNA high-throughput sequencing analysis was conducted to assess alterations in the composition of the gut microbiota. This revealed an increase in the abundance of Lactobacillus and Faecalibacterium in the pulp fermented by Bifidobacterium breve and Lacticaseibacillus casei, whereas the abundance of Sutterella decreased. Further analysis at the species level revealed that Bifidobacterium longum, Faecalibacterium prausnitzii, and Lactobacillus zeae were the dominant strains present during colonic fermentation. These results indicate a beneficial health trend associated with probiotic bacterial fermentation of red pitaya pulp, which is highly important for the development of functional products.

Preparation of a Lactobacillus rhamnosus ATCC 7469 microencapsulated-lactulose synbiotic and its effect on equol production.

Equol is a highly active product of soy isoflavones produced by specific bacteria in the human or animal colon. However, equol production is influenced by differences in the gut flora carried by the body. Our previous research has shown that a synbiotic preparation comprising the probiotic Lactobacillus rhamnosus ATCC 7469 and the prebiotic lactulose can enhance equol production by modulating the intestinal flora. Nevertheless, the harsh environment of the gastrointestinal tract limits this capability by diminishing the number of probiotics reaching the colon. Microencapsulation of probiotics is an effective strategy to enhance their viability. In this study, probiotic gel microspheres (SA-S-CS) were prepared using an extrusion method, with sodium alginate (SA) and chitosan (CS) serving as the encapsulating materials. Scanning electron microscopy (SEM) was employed to observe the surface morphology and the internal distribution of bacteria within the microcapsules. The structural characteristics of the microcapsules were investigated using Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Furthermore, the thermal stability, storage stability, probiotic viability post-simulated gastrointestinal fluid treatment, and colon release rate were examined. Finally, the impact of probiotic microencapsulation on promoting equol production by the synbiotic preparation was assessed. The results indicated that the microcapsules exhibited a spherical structure with bacteria evenly distributed on the inner surface. Studies on thermal and storage stability showed that the number of viable cells in the probiotic microcapsule group significantly increased compared to the free probiotic group. Gastrointestinal tolerance studies revealed that after in vitro simulated gastrointestinal digestion, the amount of viable cells in the microcapsules was 7 log10 CFU g-1, demonstrating good gastrointestinal tolerance. Moreover, after incubation in simulated colonic fluid for 150 min, the release rate of probiotics reached 93.13%. This suggests that chitosan-coated sodium alginate microcapsules can shield Lactobacillus rhamnosus ATCC 7469 from the gastrointestinal environment, offering a novel model for synbiotic preparation to enhance equol production.