Recent sets of evidence have described profiles of 16S rDNA sequences in host tissues, notably in fat pads that are significantly overrepresented and can serve as signatures of metabolic disease. However, these recent and original observations need to be further detailed and functionally defined. Here, using state-of-the-art targeted DNA sequencing and discriminant predictive approaches, we describe, from the longitudinal FLORINASH cohort of patients who underwent bariatric surgery, visceral, and subcutaneous fat pad-specific bacterial 16SrRNA signatures. The corresponding Porphyromonadaceae, Campylobacteraceae, Prevotellaceae, Actimomycetaceae, Veillonellaceae, Anaerivoracaceae, Fusobacteriaceae, and the Clostridium family XI 16SrRNA DNA segment profiles are signatures of the subcutaneous adipose depot while Pseudomonadaceae and Micrococcacecae, 16SrRNA DNA sequence profiles characterize the visceral adipose depot. In addition, we have further identified that a specific pre-bariatric surgery adipose tissue bacterial DNA signature predicts the efficacy of body weight loss in obese patients 5-10 years after the surgery. 16SrRNA signatures discriminate (ROC ~ 1) the patients who did not maintain bodyweight loss and those who did. Second, from the 16SrRNA sequences we infer potential pathways suggestive of catabolic biochemical activities that could be signatures of subcutaneous adipose depots that predict body weight loss.

Antimicrobial resistance (AMR) and the evolution of multiple drug-resistant (MDR) bacteria is of grave public health concern. To combat the pandemic of AMR, it is necessary to focus on novel alternatives for drug development. Within the host, the interaction of the pathogen with the microbiome plays a pivotal role in determining the outcome of pathogenesis. Therefore, microbiome-pathogen interaction is one of the potential targets to be explored for novel antimicrobials.

This review focuses on how the gut microbiome has evolved as a significant component of the resistome as a source of antibiotic resistance genes (ARGs). Antibiotics alter the composition of the native microbiota of the host by favouring resistant bacteria that can manifest as opportunistic infections. Furthermore, gut dysbiosis has also been linked to low-dosage antibiotic ingestion or subtherapeutic antibiotic treatment (STAT) from food and the environment.

Colonization by MDR bacteria is potentially acquired and maintained in the gut microbiota. Therefore, it is pivotal to understand microbial diversity and its role in adapting pathogens to AMR. Implementing several strategies to prevent or treat dysbiosis is necessary, including faecal microbiota transplantation, probiotics and prebiotics, phage therapy, drug delivery models, and antimicrobial stewardship regulation.

Competitive sports and sports nutrition, popular among amateur athletes aiming for a lean physique, have limited research on gut microbiota.

We conducted a 46-week study to analyze the consequences of fat loss and diet restrictions in 23 fitness athletes who prepared for a physique competition. Body composition, dietary intakes, serum cytokines and chemokines, and fecal samples were analyzed.

Fat loss through caloric restriction and aerobic exercise led to an increased phylogenetic diversity of gut microbiota and changes in the composition of gut microbiota, with Faecalibacterium, Lachnospiraceae, Bacteroides, and Intestinimonas showing altered abundances. Fat loss also changed the predicted microbial functions responsible for the metabolism of carbohydrates and amino acids. Consumption of energy, carbohydrates, fiber, vitamins and minerals, and various fatty acids decreased during the preparation for the competition, which was partly associated with changes in gut microbiota. Several cytokine levels decreased (IL1a, IL1b, IL10, and TFNα), and certain chemokine levels increased (GROa and RANTES). During the 23-week regain period after the competition, gut microbiota showed signs of recovery, with increased diversity compared to pre- and post-competition measurements. Most taxonomic changes returned to their baseline levels after the regain period.

The study highlights the dynamic nature of gut microbiota and its response to fat loss and regain in non-obese fitness/physique competitors and provides novel insights into how competitive sports and sports nutrition can influence the gut ecosystem.

The role of xenobiotic disruption of microbiota, corresponding dysbiosis, and potential links to host metabolic diseases are of critical importance. In this study, we used a widely prescribed antipsychotic drug, risperidone, known to influence weight gain in humans, to induce weight gain in C57BL/6J female mice. We hypothesized that microbes essential for maintaining gut homeostasis and energy balance would be depleted following treatment with risperidone, leading to enhanced weight gain relative to controls. Thus, we performed metagenomic analyses on stool samples to identify microbes that were excluded in risperidone-treated animals but remained present in controls. We identified multiple taxa including Limosilactobacillus reuteri as a candidate for further study. Oral supplementation with L. reuteri protected against risperidone-induced weight gain (RIWG) and was dependent on cellular production of a specialized metabolite, reutericyclin. Further, synthetic reutericyclin was sufficient to mitigate RIWG. Both synthetic reutericyclin and L. reuteri restored energy balance in the presence of risperidone to mitigate excess weight gain and induce shifts in the microbiome associated with leanness. In total, our results identify reutericyclin production by L. reuteri as a potential probiotic to restore energy balance induced by risperidone and to promote leanness.

Understanding the dynamic relationship between mucus-associated microbiota and host health is critical. However, studies predominantly using stool samples may not accurately represent these bacterial communities. Here, we investigated the mucus-associated microbiota in the gastrointestinal tract of mice and the terminal ileum of humans using different sample types: mucosal washes, brushes, scrapings, and intestinal contents in mice and biopsies, brushes and mucosal washes in humans. We used DNA quantification and 16S rRNA amplicon sequencing to evaluate the comparability of the information yielded from the different sample types under a controlled benchmark. In mice, mucosal washes and brushes had comparative bacterial DNA and host DNA contamination than scraping samples. Similarly, in humans, washes outperformed biopsies in bacterial DNA content. Read counts and microbiota alpha diversity remained remarkably similar in mice and between brushes and washes in humans. The composition of the microbiota varied based on the subsegment and sample type in mice and sample type in humans. We conclude that washes and brushes reduce host contamination without inducing substantial compositional bias when sampling mucosal microbiota. Our findings suggest that mucosal washes and brushes are a viable alternative to biopsies in humans and scrapings in mice, thereby improving the transferability of results across hosts. Our study highlights the importance of focusing on mucus-associated microbiota to better capture host-microbiome interactions at their closer interface.

Excessive intake of dietary fats is strongly associated with an increased risk of various chronic diseases, such as obesity, diabetes, hepatic metabolic disorders, cardiovascular disease, chronic intestinal inflammation, and certain cancers. A significant portion of the adverse effects of high-fat diet on disease risk is mediated through modifications in the gut microbiota. Specifically, high-fat diets are linked to reduced microbial diversity, an overgrowth of gram-negative bacteria, an elevated Firmicutes-to-Bacteroidetes ratio, and alterations at various taxonomic levels. These microbial alterations influence the intestinal metabolism of small molecules, which subsequently increases intestinal permeability, exacerbates inflammatory responses, disrupts metabolic functions, and impairs signal transduction pathways in the host. Consequently, diet-induced changes in the gut microbiota play a crucial role in the initiation and progression of chronic diseases. This review explores the relationship between high-fat diets and gut microbiota, highlighting their roles and underlying mechanisms in the development of chronic metabolic diseases. Additionally, we propose probiotic interventions may serve as a promising adjunctive therapy to counteract the negative effects of high-fat diet-induced alterations in gut microbiota composition.

Micro(nano)plastics (M/NPs) are pervasive in marine environments. Benzo[a]pyrene (B[a]P), a typical polycyclic aromatic hydrocarbon (PAH), possesses teratogenic, mutagenic, and carcinogenic properties. B[a]P can accumulate on M/NPs, altering their toxicity. This study investigated individual and combined effects of M/NPs and B[a]P on the intestinal regeneration of the benthic invertebrate Apostichopus japonicus. Eviscerated sea cucumbers were exposed to 0.1 mg L-1 M/NPs (80 nm [NP80] or 20 μm [MP20]) and/or 0.03 μg L-1 B[a]P for 28 days. Cell proliferation, antioxidant and immunoenzyme activity, gene expression, and microbial community in the regenerated intestine were assessed. It demonstrated that combined exposure prolonged regeneration process, leading to increased oxidative stress and intestinal damage. Differential gene expression analysis revealed that co-exposure and single NP80 exposure both significantly changed translation-related processes, while single MP20 exposure primarily affected lipid metabolism. All treatments significantly altered the intestinal microbiota. Under the MP20+B[a]P treatment, Ralstonia abundance significantly increased, while Cobetia and Paracoccus abundances decreased. In general, co-exposure exerted more detrimental effects on intestinal regeneration than any single exposure, with MP20+B[a]P demonstrating more severe impacts. This study provides novel insights into the biotoxicity of M/NPs and B[a]P, contributing to better understanding of the detriments of microplastics and PAHs on marine benthic invertebrates.

Restriction of dietary carbohydrates, fat and/or protein is often used to reduce body weight and/or treat (metabolic) diseases. Since diet is a key modulator of the human gut microbiome, which plays an important role in health and disease, this review aims to provide an overview of current knowledge of the effects of macronutrient-restricted diets on gut microbial composition and metabolites. A structured search strategy was performed in several databases. After screening for inclusion and exclusion criteria, thirty-six articles could be included. Data are included in the results only when supported by at least three independent studies to enhance the reliability of our conclusions. Low-carbohydrate (<30 energy%) diets tended to induce a decrease in the relative abundance of several health-promoting bacteria, including Bifidobacterium, as well as a reduction in short-chain fatty acid (SCFA) levels in faeces. In contrast, low-fat diets (<30 energy%) increased alpha diversity, faecal SCFA levels and abundance of some beneficial bacteria, including Faecalibacterium prausnitzii. There were insufficient data to draw conclusions concerning the effects of low-protein (<10 energy%) diets on gut microbiota. Although the data of included studies unveil possible benefits of low-fat and potential drawbacks of low-carbohydrate diets for human gut microbiota, the diversity in study designs made it difficult to draw firm conclusions. Using a more uniform methodology in design, sample processing and sharing raw sequence data could foster our understanding of the effects of macronutrient restriction on gut microbiota composition and metabolic dynamics relevant to health. This systematic review was registered at https://www.crd.york.ac.uk/prospero as CRD42020156929.

Obesity, characterized by excessive adipose tissue accumulation, has become a global health challenge with rapidly increasing prevalence. It contributes significantly to metabolic disorders including insulin resistance (IR). Renshen-zhuye decoction (RZD), a traditional Chinese medicine formula historically used for diabetes, shows potential for improving metabolic parameters, but its effects and mechanisms in obesity and insulin resistance remain unclear.

This study aimed to evaluate the therapeutic benefits of RZD on obesity and insulin resistance, and to elucidate the underlying mechanisms through which it improves glucose and lipid metabolism.

The role of RZD was evaluated in a high-fat diet (HFD) mouse model. The formula was characterized using UPLC-MS. Comprehensive analyses including histopathological staining, immunofluorescence, biochemical assays, 16S rRNA gene sequencing of gut microbiota, and non-targeted metabolomic analysis were performed. To validate the role of gut microbiota, we employed antibiotic treatment (ABX) to deplete intestinal flora and conducted fecal microbiota transplantation (FMT) experiments.

RZD treatment dose-dependently alleviated HFD-induced dyslipidemia and insulin resistance, improving glucose tolerance, insulin sensitivity, and energy expenditure. Gut microbiota analysis revealed that RZD significantly modulated the composition of intestinal flora and their metabolic profiles. Additionally, RZD reduced intestinal and systemic inflammation by enhancing intestinal barrier integrity, particularly through increased expression of tight junction proteins such as Occludin. Importantly, the beneficial effects of RZD on weight management and glucose homeostasis were antagonized by antibiotic intervention, while FMT experiments confirmed that these improvements were mediated through gut microbiota modulation.

This study provides new insights into RZD's modulatory effects on gut microbiota and subsequent improvements in obesity-related metabolic parameters. RZD alleviates HFD-induced obesity and insulin resistance in mice by modulating gut microbiota composition and function, which subsequently improves intestinal barrier integrity, reduces inflammation, and enhances metabolic homeostasis.

Monosodium glutamate (MSG) has become one of the most widely used food additives in the global food supply. Although it has been classified for decades as a food ingredient that is generally recognized as safe, concerns about the health impacts of chronic MSG use, especially its potential effect on weight, are still ongoing. This comprehensive review summarizes the available human and animal evidence, highlighting potential mechanisms linking MSG use to weight gain or obesity, and discusses challenges and future research directions. Because of MSG intake worldwide as well as hidden MSG in food labeling, there is a pressing need for a mechanistic understanding of the health impacts of MSG use especially on weight. To generate robust scientific evidence and to clarify public concerns, rigorous mechanistic studies and randomized controlled clinical trials are warranted.

Previous evidence suggests that gut dysbiosis plays an important role in the development and progression of sarcopenia and sarcopenic obesity (SO), but evidence supporting this association is lacking. Thus, this study aimed to investigate the characteristics of gut microbiota in older people with sarcopenia and SO.

A total of 1558 older adults (age ≥65 years) from a community-based cohort in Shanghai, China, underwent sarcopenia screening using the SARC-F questionnaire, with 351 participants completing further assessment. On the basis of the Asian Working Group for Sarcopenia 2019 and the World Health Organization obesity criteria, 60 participants were categorized into three groups: SO (n = 20), sarcopenia without obesity (Sar, n = 18), and controls (Con, n = 22). Gut microbiota composition was analyzed using 16S rRNA sequencing (V3-V4 regions).

Significant differences in the diversity and composition of the gut microbiota were observed in the Sar and SO groups. A reduction in alpha diversity (Chao1 and ACE indices) was found in the SO group. Beta diversity based on unweighted Unifrac PCoA was significantly different among the three groups. LEfSe analysis identified 39 taxa with significant differential abundances across groups. The Sar group exhibited enrichment of Christensenellaceae_R-7_group, Alistipes, Ruminococcus, Odoribacter, Prevotellaceae_UCG-001, Hungatella, Family_XIII_AD3011_group, Anaerotruncus, Ruminiclostridium, and Oxalobacter, along with their high taxonomic classifications. Meanwhile, Enterobacteriaceae, Allisonella, and Peptoclostridium were enriched in the SO group. Feature selection via Boruta algorithm identified five and four discriminatory taxa to construct random forest models, effectively distinguishing individuals with Sar and SO from Con. Key predictors for Sar included reduced Enterococcus, Enterobacter, and Hungatella and increased Odoribacter and Christensenellaceae_R-7_group. Conversely, SO was characterized by decreased Enterobacter, Alloprevotella, and Enterococcus and increased Allisonella. Five-fold cross-validation confirmed robust diagnostic efficacy, achieving AUCs of 0.860 (95 % CI: 0.786-0.996) for Sar and 0.826 (95 % CI: 0.735-0.970) for SO.

This study demonstrated that the gut microbiota of SO and Sar have distinct diversity and composition profiles. The results provide new insights into the role of gut microbiota in SO, highlighting its potential as a therapeutic target in this condition.

This study investigated the relationship between BMI and microorganism profiles, with a particular focus on gut microorganisms in patients with PJI following total hip arthroplasty (THA). It also explored comorbidities, that may contribute to these variations.

This study included all patients treated at our institution for a PJI of a THA between 1996 and 2021. Patients were categorized into four distinct BMI groups: <30; 30-34.9; 35-39.9; ≥ 40. Bivariate and logistic regression analysis were conducted, with presentation of odds ratio (OR) and 95% confidence interval (CI).

A total of 3645 hip PJI cases were recruited for the final analysis. Patients with a BMI ≥ 40 had approximately a ten fold higher risk for Streptococcus dysgalactiae (p < 0.001; OR = 9.92; 95% CI 3.87-25.44) and a seven fold higher risk for Proteus mirabilis (p < 0.001; OR = 7.43; 95% CI 3.13-17.67) and Klebsiella pneumoniae (p < 0.001; OR = 6.9; 95% CI 2.47-19.31). Furthermore, polymicrobial infections (p < 0.001; OR = 2.17; 95% CI 1.50-3.15) were found to be significantly more prevalent in patients with a BMI ≥ 40.

Obese patients (BMI ≥ 30) displayed a distinct microorganism profile in hip PJIs, mainly dominated by Firmicutes and Proteobacteria. Comorbidities such as diabetes, hypertension, and hyperlipidaemia may contribute to a leaky gut syndrome, increasing PJI risk caused by gut microorganisms. Optimizing comorbidities may help reduce the risk of hip PJI. Further research is needed to clarify the relationship between obesity, gut microbiome alterations and hip PJI development.

Currently, many research efforts and product developments focus on goat milk, while studies on the development and probiotic function of sheep milk remain limited. In this study, the effects of Lactobacillus rhamnosus NM-94 on the physicochemical properties, viable count, texture, microrheology, flavor, and quality detection and intestinal flora of fermented milk were analyzed by adding or not adding L. rhamnosus NM-94 to 2 starter cultures. The results showed that the addition of L. rhamnosus NM-94 to sheep milk significantly reduced fermentation time by 2 h (12 h vs. 14 h). At 21 d of storage, the count of viable bacteria in fermented sheep milk supplemented with L. rhamnosus NM-94 (0.61 ± 0.06 × 109 cfu/mL) was surprisingly higher than that of the control milk (0.35 ± 0.03 × 109 cfu/mL). During the microrheological analysis of the fermentation stage, the elastic index, macroscopic viscosity index, and solid-liquid balance values of fermented sheep milk supplemented with L. rhamnosus NM-94 were greater than those of the control milk, indicating that the fermented sheep milk supplemented with L. rhamnosus NM-94 had a more stable gel structure and viscosity. In mice, fermented sheep milk supplemented with L. rhamnosus NM-94 has a variety of beneficial intestinal microorganisms and potential probiotic functions. This study provides new ideas for improving the function of sheep milk and expanding the sheep milk industry.

Diabetes mellitus, a most common endocrine disorder of glucose metabolism, has become a global epidemic and poses a serious public health threat with an increased socio-economic burden. Escalating incidence of diabetes is correlated with changes in lifestyle and food habits that cause gut microbiome dysbiosis and β-cells damage, which can be addressed with dietary interventions containing probiotics. Hence, the search for probiotics of human origin with anti-diabetic, anti-AGE, and anti-ACE potentials has gained renewed interest for the effective management of diabetes and its associated complications. The present study used an alloxan (AXN)-induced diabetic rat model to investigate the effects of potential probiotic Lacticaseibacillus casei MKU1, Lactiplantibacillus pentosus MKU3, and Lactiplantibacillus plantarum MKU7 administration individually on physiochemical parameters related to diabetic pathogenesis. Experimental animals were randomly allotted into six groups viz. NCG (control), DCG (AXN), DGM (metformin), DGP1 (MKU1), DGP2 (MKU3), and DGP3 (MKU7), and biochemical data like serum glucose, insulin, AngII, ACE, HbA1c, and TNF-α levels were measured until 90 days. Our results suggest that oral administration with MKU1, MKU3, or MKU7 significantly improved serum insulin levels, glycemic control, glucose tolerance, and body weight. Additionally, β-cell mass was increased by preserving islet integrity in Lactobacillus-treated diabetic rats, whereas TNF-α (~40%), AngII (~30%), and ACE levels (~50%) were strongly inhibited and enhanced sIgA production (5.8 folds) abundantly. Furthermore, Lactobacillus administration positively influenced the gut microbiome with a significant increase in the abundance of Lactobacillus species and the beneficial Bacteroides uniformis and Bacteroides fragilis, while decreased the pathogenic Proteus vulgaris and Parabacteroides distasonis. Among the probiotic treatment groups, L. pentosus MKU3 performed greatly in almost all parameters, indicating its potential use for alleviating diabetes-associated complications.

Obesity has become a global health crisis driven by genetic, environmental, and lifestyle factors, often linked to gut microbiome imbalances. Probiotics, particularly Lactobacillus and Bifidobacterium strains, have shown promise in clinical trials by promoting weight loss, improving lipid profiles, and addressing gut dysbiosis associated with obesity. This review surveys the literature on the microbiome and obesity, emphasizing the clinical relevance of probiotics in treatment strategies. Our comprehensive PubMed search highlights the mechanisms through which probiotics influence metabolic health, including their effects on inflammation and appetite regulation. We also explore promising future research directions and the potential for integrating probiotics into clinical practice. While results are encouraging, the evidence is limited by strain variability, small sample sizes, short trial durations, and individual differences in microbiota composition. More extensive, long-term studies with standardized methods are crucial to confirm the effectiveness of probiotics as viable anti-obesity treatments.

Microbiota-metabolome interactions play a crucial role in host physiological regulation and metabolic homeostasis. The aim of this study was to investigate that sex induces alterations in rumen microbial community composition and metabolite profiles in lambs and the influence on body weight. This study aimed to demonstrate that sex- induced alterations in rumen microbial community and metabolite profiles and blood indices and their linkage to growth performance in lambs.

This study examined (growth indices, serum indices, rumen fermentation parameters, rumen fluid microbiota community and metabolome profiles) in 180 Hu lambs (90 males, and 90 females) with the same age and diet. At six months, male lambs showed significantly greater body weight, serum indices (glutamic pyruvic transaminase, glutamic oxalacetic transaminase, growth hormone, glucagon-like peptide 1, and ghrelin), and molar percentage of propionic acid, isobutyric acid, butyric acid, isovaleric acid and valeric acid compared to female. However, male had lower VFA molar concentrations (acetic acid, propionic acid, butyric acid, and TVFAs), acetic acid/propionic acid, and VFA molar percentage (acetic acid) than female. Significant sex-related differences were observed in rumen microbiota and metabolic enrichment between genders. Moreover, compared with the females lambs, the relative abundance of Succiniclasticum, uncultured_rumen_bacterium, NK4 A214_group, Veillonellaceae_UCG_001 and Butyrivibrio in the male lambs has been significantly increased, while the relative abundance of Prevotella has been significantly decreased (P < 0.05). Notably, there were significant rumen microbiota-metabolite interactions, especially Firmicutes and Bacteroidota as dominant phyla in the sheep rumen with significant differences in correlation with rumen metabolic modules. Additionally, there are pronounced correlations among the microbiota, particularly within the Firmicutes phylum. Furthermore, the up-regulated metabolites in the rumen fluid of male lambs were predominantly enriched in the amino acid metabolite pathway, and these metabolites exhibited a significant positive correlation with body weight. However, the metabolites that were up-regulated in ewe lambs were predominantly enriched in the lipid metabolic pathway, and these metabolites exhibited a significant negative correlation with body weight. Moreover, lamb rumen microbial markers (Lachnospiraceae_UCG_008, Saccharofermentans, unclassified_Clostridia, Christensenellaceae_R_7_group, Anaerovorax, Mogibacterium, and unclassified_Erysipelotrichaceae) and metabolic markers (C75, 4-Coumarate, Flibanserin,3-Amino-5-mercapto-1,2,4-triazole, 1,3-Propane sultone, Fingolimod phosphate ester, S-,) were significantly positively correlated with body weight, but lamb rumen microbial markers (Anaeroplasma, unclassified_Acholeplasmataceae, uncultured_rumen_bacterum_4c28 d_15) and metabolic markers (Mozenavir, Reduced riboflavin, PG(18:2(9Z,12Z)/0:0), Cowanin) were significantly negatively correlated body weight.

This study shows that sex-induced alterations in rumen microbial communities and metabolite profiles, adapting to the growth and development of lambs. The findings may help develop targeted strategies to optimize sheep rumen microbiota and improve productivity.

Alcohol-associated liver disease (ALD)-encompassing conditions including steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma-refers to hepatic damage arising from excessive or hazardous alcohol consumption, and is now recognized as a significant global health burden. Although the mechanisms underlying ALD remain incompletely understood, several pathways have been substantiated over the last five decades, notably the involvement of intestinal microorganisms and the involvement of the gut-liver axis in alcohol metabolism and ALD pathogenesis. Ethanol intake disrupts the intestinal microbial balance and compromises the gut barrier, resulting in increased permeability to microbial products. The subsequent translocation of microbial metabolites and other antigenic substances to the liver activates hepatic immune responses, thereby contributing to liver injury. In addition, gastrointestinal hormones are also implicated in ALD progression through various mechanisms. Although no therapies for ALD have been approved by the Food and Drug Administration, various therapeutic strategies targeting the intestinal microbiota and gut barrier have been identified. In conclusion, this review discusses the role of the gut-liver axis in alcohol metabolism and ALD pathogenesis and explores the emerging therapeutic strategies.

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.

Coccidiosis, caused by Eimeria protozoa, is a severe intestinal parasitic disease that results in substantial economic losses to the global poultry industry annually. The gut microbiota plays a crucial role in host health, metabolism, immune function, and nutrient absorption in chickens. Recent studies have focused on the effects of Eimeria tenella's (E. tenella) acute infection period on host health. However, recovery conditions, cecal microbiota composition, and functional differences in the ceca of chickens with varying resistance to E. tenella remain poorly understood during the recovery period after infection. This study aimed to compare growth performance, cecal histopathology, and the cecal microbiota characteristics in control (R_JC), resistant (R_JR), and susceptible (R_JS) chickens during recovery, using metagenomic sequencing. The results revealed significant differences in both cecal tissue structure and growth performance between the different groups during recovery. Although no significant differences were observed in microbial alpha diversity among the groups, sequencing analysis highlighted notable changes in microbial composition and abundance. Bacteroidetes, Firmicutes, and Proteobacteria were the predominant phyla in chicken cecal contents; however, Firmicutes abundance was lower in the R_JS group than in the R_JC and R_JR groups. Further analysis, combining linear discriminant analysis effect size (LEfSe) and differential heatmap analysis, identified Bacteroides_fluxus, Ruminococcus_flavefaciens, and Bacteroides_sp_CACC_737 as dominant microorganisms in the R_JR group (p < 0.05) compared to both the R_JC and R_JS groups. In contrast, Sutterella_sp_AM11-39, Bacteroides_sp_43_108, Mycobacterium, Mycoplasma_arginini, and Chlamydia dominated in the R_JS group, while Butyricimonas, Butyricimonas_sp_Marseille-P3923, and Flavonifractor_plautii were significantly reduced in the R_JS group (p < 0.05). Additionally, beneficial cecal microorganisms such as Flavonifractor_sp__An10, Pseudoflavonifractor, and Faecalicoccus were significantly decreased in both the R_JR and R_JS groups (p < 0.05) compared to the R_JC group. Predictive functional analysis using the KEGG and CAZy databases further indicated that the cecal microbiota in the R_JR group exhibited enhanced metabolism-related pathways, whereas these pathways were significantly diminished in the R_JS group, potentially influencing the recovery process from coccidial infection. These findings provide valuable insights into the cecal microbiota's role during recovery from E. tenella infection and deepen our understanding of the impact of coccidial infections on host health.

There is substantial evidence linking migraines to gastrointestinal (GI) issues. Conditions such as irritable bowel syndrome and colitis often co-occur with migraines and GI symptoms are common among migraine patients. However, the evidence supporting the efficacy of gut microbiome-targeted therapies for managing migraines is limited. This systematic review aimed to describe the existing evidence of the gut microbiome in patients with migraine compared to healthy individuals. Additionally, it sought to examine how therapies targeting the gut microbiome including prebiotics, probiotics and synbiotics, might influence clinical outcomes.

We performed searches on Embase, PubMed, and the Cochrane Library to identify studies in migraines and the gut microbiome, focusing on those which investigated the gut microbiome composition and gut microbiome-targeted therapies. Key data was extracted and analysed including study details, patient demographics, migraine type, comorbidities, and clinical outcomes. For gut microbiome composition studies, bacterial diversity and abundance was noted. For gut microbiome-targeted therapies studies, treatment types, dosages, and patient outcomes was recorded.

A significant difference between various genera of microbes was reported between migraine patients and controls in several studies. Bacteroidetes (also named Bacteroidota), proteobacteria, and firmicutes (also named Bacillota) phyla groups were found significantly abundant in migraine, while studies were conflicted in the abundance of Actinobacteria and Clostridia with regards to increased migraine risk in migraine patients. Patients with migraine had a gut microbiome with reduced species number and relative abundance, as well as a distinct bacterial composition compared to controls. Synbiotic and synbiotic/probiotic combination treatments have been shown in five randomised controlled trials and one open label pilot study to significantly decrease migraine severity, frequency, duration and painkiller consumption.

The significant alterations in microbial phyla observed in migraine patients suggest a potential microbial signature that may be associated with migraine risk or chronic progression. However, the mechanistic underpinnings of these associations remain unclear. This systemic review found that probiotic and synbiotic/probiotic combination therapies may be promising interventions for migraine management, offering significant reductions in migraine frequency and painkiller use. Future randomised controlled studies are needed to evaluate the optimal length of treatment and impact on patient related quality of life.

Extracellular vesicles (EVs), nanoparticles secreted by both gram-negative and gram-positive bacteria, carry various biomolecules and cross biological barriers. Gut microbiota-derived EVs are currently being investigated as a communication mechanism between the microbiota and the host. Few clinical studies, however, have investigated gut microbiota-derived EVs. Here, we show that machine learning models were able to accurately distinguish gut microbiota and respective microbiota-derived EV samples according to their taxonomic composition both within each data set (area under the curve [AUC] 0.764-1.00) and in a cross-study setting (AUC 0.701-0.997). These results show that gut microbiota-derived EVs form a distinct taxonomic entity from gut microbiota. Thus, conventional gut microbiota composition may not correctly reflect communication between the gut microbiota and the host unless microbiota-derived EVs are reported separately.IMPORTANCEGut microbiota-derived extracellular vesicles (EVs) have been suggested to be a communication mechanism between the gut microbiota and the human body. However, the data on EV secretion from the gut microbiota remain limited. To investigate and compare the composition of gut microbiota-derived EVs to gut microbiota composition, we used a machine learning approach to classify 16S rRNA gene sequencing data in seven clinical data sets incorporating both gut microbiota and gut microbiota-derived EV samples. The results of the study show that microbiota-derived EVs form a separate taxonomic entity from the gut microbiota. Gut microbiota-derived EVs should be included in clinical studies that investigate gut microbiota to gain more comprehensive insight into gut microbiota-host communication.

Constipation is common in patients with acute ischemic stroke, yet its incidence and prognosis remain unknown. Herein, we investigate the incidence of new-onset constipation and its risk factors and relationship with stroke severity and prognosis.

This prospective study enrolled 358 patients diagnosed with acute ischemic stroke. The Constipation Scoring System was used to assess new-onset constipation during hospitalization. Demographics, medical histories, clinical data, laboratory parameters, and medication use were compared between non-constipation and constipation groups. Univariate and multivariate logistic regression and multiple linear regression were used to explore potential influencing factors and prognosis.

The cumulative incidence of new-onset constipation during was 41.6 %. Its occurrence was closely associated with multiple demographic factors and laboratory markers. Binary logistic regression identified age (P = 0.002), eosinophil count (P = 0.004), and modified Rankin scale (mRS) scores at admission (P = 0.048) as significant predictors. The NIHSS (β = 0.179, P = 0.001) and mRS (β = 0.168, P = 0.016) scores at admission significantly positively predicted the Constipation Assessment Scale. NIHSS scores at admission (β = 0.300, P < 0.001) also positively predicted constipation severity at six-month follow-up.

New-onset constipation is a common complication of acute ischemic stroke hospitalization. NIHSS, mRS, and water swallowing test scores at admission can predict the incidence and severity of constipation during hospitalization and at the 6-month follow-up. These findings provide clinical insights for early risk assessment and intervention to mitigate constipation-related complications in patients with stroke.

Queen bee larvae (QBL) have been consumed as both a traditional food and medicine in China for thousands of years; however, their specific benefits for human health, particularly their potential anti-obesity property, remain underexplored. This study investigated the anti-obesity effect of QBL freeze-dried powder (QBLF) on high-fat diet (HFD) induced obesity in mice and explored the underlying mechanisms. Our findings showed that QBLF effectively reduced body weight, fasting blood glucose levels, lipid accumulation, and inflammation in HFD mice. 16S rRNA sequencing revealed that QBLF significantly modulated the gut microbiota disrupted by an HFD, notably increasing the relative abundance of beneficial microbes such as Ileibacterium, Clostridium sensu stricto 1, Incertae sedis, Streptococcus, Lactococcus, Clostridia UCG-014, and Lachnospiraceae UCG-006, which were inversely associated with obesity-related phenotypes in the mice. RNA sequencing analysis further demonstrated that QBLF intervention upregulated the expression of genes involved in liver lipid metabolism, including Pck1, Cyp4a10, Cyp4a14, and G6pc, while downregulating genes associated with the inflammatory response, such as Cxcl10, Ccl2, Traf1, Mapk15, Lcn2, and Fosb. These results suggested that QBLF can ameliorate HFD-induced obesity through regulating the gut microbiota, promoting liver lipid metabolism, and reducing inflammatory response.

Aquatic environments are frequently contaminated with nanoplastics (NPs) ranging from 1-100 nm generated by plastic aging, but their bio-enrichment and toxicological impacts remain poorly understood. This study investigates how chronic exposure to carboxylated polystyrene nanoplastics (PNPs) alters gut microbiota composition and function in zebrafish (Danio rerio). Adult zebrafish were exposed to 50 nm PNPs at concentrations of 0.1, 1.0, and 10 mg/L for 14 and 28 days, followed by gut microbiota analysis using 16S rRNA gene sequencing. PNP exposure altered gut microbiota composition, including an increase in Proteobacteria abundance and a decrease in Firmicutes, Bacteroidetes, and the inflammation-related genus Alistipes. Beneficial probiotics such as Faecalibacterium, Streptococcus, Bifidobacterium, and Lachnospira were diminished, while pathogenic bacteria proliferated. TEM imaging revealed the internalization of PNP particles within intestinal tissues resulted in vacuolation, suggesting potential epithelial damage. Co-occurrence network patterns of gut microbiota greatly decreased during treatment with NPs. The neutral community model showed that among PNP treatments, 0.1 mg/L led to a less predictable (stochastic assembly process). PNP exposure led to increased predicted microbial functions (via PICRUSt2) related to xenobiotic metabolism, infection pathways, and lipopolysaccharide (LPS) production, while RNA transport and N-glycan biosynthesis were decreased. However, pathways related to microbial antioxidants exhibited significant variation across different PNP levels. These results provide critical insights into the toxicological impacts of chronic PNP exposure on fish gut health, highlighting the potential risks to aquatic ecosystems and human health.

The pathogenesis of obesity is complex and incompletely understood, with an underlying interplay between our genetic architecture and obesogenic environment. The public understanding of the development of obesity is shrouded in myths with widespread societal misconceptions. Body Mass Index (BMI) is a highly heritable trait. However, despite reports from recent genome-wide association studies, only a small proportion of the overall heritability of BMI is known to be lurking within the human genome. Other non-genetic heritable traits may contribute to BMI. The gut microbiome is an excellent candidate, implicating complex interlinks with hypothalamic control of appetite and metabolism via entero-endocrine, autonomic, and neuro-humeral pathways. The neonatal gut microbiome derived from the mother via transgenerational transmission (vaginal delivery and breastfeeding) tends to have a permanence within the gut. Conversely, non-maternally derived gut microbiota manifest mutability that responds to changes in lifestyle and diet. We should all strive to optimize our lifestyles and ensure a diet that is replete with varied and unprocessed plant-based foods to establish and nurture a healthy gut microbiome. Women of reproductive age should optimize their gut microbiome, particularly pre-conception, ante- and postnatally to enable the establishment of a healthy neonatal gut microbiome in their offspring. Finally, we should redouble our efforts to educate the populace on the pathogenesis of obesity, and the role of heritable (but modifiable) factors such as the gut microbiome. Such renewed understanding and insights would help to promote the widespread adoption of healthy lifestyles and diets, and facilitate a transition from our current dispassionate and stigmatized societal approach towards people living with obesity towards one that is epitomized by understanding, support, and compassion.

Exercise and diet modulate the gut microbiota, which is involved in the regulation of orthopaedic diseases and synthesises a wide range of metabolites that modulate cellular function and play an important role in bone development, remodelling and disease. G protein-coupled receptors (GPCRs), the largest family of transmembrane receptors in the human body, interact with gut microbial metabolites to regulate relevant pathological processes. This paper provides a review of different dietary and exercise effects on the pathogenic gut microbiota and their metabolites associated with GPCRs in orthopaedic diseases. RESULTS: Generally, metabolites produced by gut microbiota contribute to the maintenance of bone health by activating the corresponding GPCRs, which are involved in bone metabolism, regulation of immune response, and maintenance of gut flora homeostasis. Exercise and diet can influence gut microbiota, and an imbalance in gut microbiota homeostasis can trigger a series of adverse immune and metabolic responses by affecting GPCR function, ultimately leading to the onset and progression of various orthopaedic diseases. Understanding these relationships is crucial for elucidating the pathogenesis of orthopaedic diseases and developing personalised probiotic-based therapeutic strategies. In the future, we should further explore how to prevent and treat orthopaedic diseases through GPCR-based modulation of gut microbes and their interactions. The development of substances that precisely modulate gut microbes through different exercises and diets will provide more effective interventions to improve bone health in patients.

Inflammatory bowel disease (IBD) is an idiopathic, lifelong, and devastating chronic inflammatory disease of the gastrointestinal tract. Berberine, an alkaloid extracted from the Chinese herb Huanglian, is a pharmaceutical ingredient with antibacterial, anti-inflammatory, and antiviral pharmacological effects in Chinese medicine. However, direct administration of berberine requires high doses due to its low bioavailability and high waste in the stomach. In this study, we prepared berberine-loaded pH-responsive Eudragit® FS 30D-attapulgite (FS-ATT) microspheres for the targeted treatment of colitis. The microspheres had pH-responsive release behavior, with minimal berberine release (about 5.97%) in simulated gastric fluid and high berberine release in simulated colonic fluid (about 69.27%). In addition, it was revealed by in vivo biological evaluations that, compared with drugs in an equivalent solution form taken orally, a significant improvement in IBD symptoms was observed after oral administration of drug-loaded FS-ATT microspheres, leading to an increase in the diversity of intestinal microbiota, inhibition of inflammatory cytokines, and enhanced therapeutic effects of berberine. The pH-responsive FS-ATT microspheres could offer a promising drug delivery platform for managing and treating many gastrointestinal diseases.

Urolithins (Uros), a series of natural polyphenols derived from ellagic acid through gut bacteria metabolism, have gathered significant attention due to their diverse bioactivities such as maintaining mitochondrial health and anti-inflammatory and antioxidative effects. However, the ability to metabolize Uros varies among individuals. This Review provides a comprehensive insight into the synthesis, encapsulation and bioactivities of Uros, focusing on their biotransformation in vivo. We highlight the critical role of gut microbiota in the biotransformation of urolithins, including primary bacterial species such as Gordonibacter urolithinfaciens, Enterocloster bolteae and Enterococcus faecium. Furthermore, the therapeutic potential of Uros in alleviating neurodegenerative diseases, cancer, and Duchenne muscular dystrophy is discussed. Finally, several encapsulation strategies for enhancing the solubility and bioavailability of Uros are summarized. Future research direction includes identifying key genes involved in Uros biotransformation, elucidating the bioactive mechanisms of Uros, and improving their bioavailability. In conclusion, we synthesized biosynthetic pathways and bioactive properties of Uros for better utilization in health management.

Acute malnutrition still affects millions of children under five years of age globally each year and contributes to approximately half of all annual childhood deaths. A considerable proportion of patients who recover from acute malnutrition experience poor health and nutrition and eventually relapse after they are discharged from community management of acute malnutrition programs. A microbiota-directed complementary food (MDCF) showed a superior effect compared to standard ready-to-use supplementary food (RUSF) in terms of ponderal growth and potential benefit for bacterial taxa that were correlated with weight-for-height z-score (WHZ). This paper describes a protocol for the MDCF phase III trial on a larger African sample for promoting sustained recovery.

This study is an individually controlled open-label phase III trial to determine the efficacy of MDCF on programmatic and sustained recovery compared to standards RUTF and RUSF. Eligible MAM children will be randomly assigned to MDCF or RUSF and those with SAM to MDCF or RUTF. Supplementation and follow-up visits will be performed following national guidelines for acute malnutrition management. Primary outcomes are programmatic recovery at 12 weeks after enrollment and sustained recovery at 12 weeks after recovery. The secondary outcomes included the mean WHZ, weight-for-age z score, height-for-age z score change, average length of stay, nonresponse, failure and dropout.

The present study is designed to investigate the efficacy of a microbiota-targeted food in treating acute uncomplicated malnutrition and preventing relapses. It will provide evidence as a phase III clinical trial.

Clinicaltrials.gov Protocol registration and results system (NCT05586139). Registered on 2022-10-14. https://register.

gov/ .

Ginseng soluble dietary fiber (GSDF) has been shown to have good physicochemical properties; however, its in vivo benefits in obesity are yet to be fully elucidated.

To explore this, C57BL/6J obese mice were given metformin hydrochloride and different doses of GSDF for 60 days. The levels of blood lipids and inflammatory factors were detected by ELISA, and the pathological alterations were detected through the application of HE staining. The level of adipose tissue protein in epididymis was detected by Western blotting and through the effects of 16S rRNA sequencing on gut microbiota.

The results showed that GSDF significantly improved basal physiological indices, lipid levels, and serum cytokine levels in the obese mice. GSDF increased the expression levels of PPAR-γ, AMPK, and P-AMPK proteins, and lowered the expression of IL-1β, TNF-α, and other proteins in the adipose tissues of the epididymis, in turn inhibiting adipogenesis and ameliorating lipid metabolism disorders. By lowering the Firmicutes/Bacteroidetes ratio in the gut and altering the abundance of thick-walled bacteria and mycobacterium, the abundance of species such as Lactobacillus, Alloprevotella, and Faecalibaculum was altered to improve cecum health.

These results suggest that GSDF may have a positive effect on growth, obesity, and cecal health in obese mice.

As the main active ingredient of the first FDA-approved phytochemical drug, epigallocatechin gallate (EGCG) can effectively alleviate glucolipid metabolic disorders. However, existing studies mainly focuses on the treatment of EGCG in disease models, with limited focus on its preventive effect on diseases in healthy models.

This study investigated how EGCG prevents and alleviates T2DM through gut microbiota and multi-organ interactions in Wistar healthy rats and GK T2DM rats.

The GK T2DM rat strain was established through repeated selective breeding of Wistar rats with glucose intolerance. Whether and how EGCG prevents and alleviates T2DM were evaluated, including glucose production and absorption efficiency, glucose transport, glucose metabolism, glucose excretion, T2DM-related tissue damage, gut microbiota, and liver transcriptome.

The health benefits of EGCG are primarily reliant on the involvement of the gut microbiota. Our study showed that although the specific microbial communities involved differ, the bidirectional interaction between EGCG and gut microbiota is widespread in healthy rats and T2DM rats. EGCG intervention elevated the relative abundance of specific microbial communities, which in turn promoted the metabolic processing of EGCG in the gut, producing numerous EGCG metabolites that may contribute to preventing and alleviating T2DM. In healthy rats, EGCG intervention selectively enhanced insulin secretion and serum insulin levels to prevent T2DM. In T2DM rats, EGCG intervention selectively lowered blood glucose levels, improved insulin resistance, delayed glucose production and absorption, and promoted urinary glucose excretion to alleviate T2DM. In both healthy and T2DM rats, EGCG intervention universally reduced gut microbiota-derived lipopolysaccharides, maintained systemic oxidative stress homeostasis, alleviated liver and kidney damage, increased muscle glycogen content, and promoted beige thermogenesis in white fat, thus demonstrating potential for preventing and alleviating T2DM.

As a natural active ingredient, EGCG could prevent and alleviate T2DM through gut microbiota and multi-organ interactions.

The importance of the microbiome, particularly the gut microbiota and its implications for health, is well established. However, an increasing number of studies further strengthen the link between an imbalanced gut microbiota and a greater predisposition to different diseases. The gut microbiota constitutes a fundamental ecosystem for maintaining human health. Its alteration, known as dysbiosis, is associated with a wide range of conditions, including intestinal, metabolic, immunological, or neurological pathologies, among others. In recent years, there has been a substantial increase in knowledge about probiotics-bacterial species that enhance health or address various diseases-with numerous studies reporting their benefits in preventing or improving these conditions. This review aims to analyze the most common pathologies resulting from an imbalance in the gut microbiota, as well as detail the most important and known gut probiotics, their functions, and mechanisms of action in relation to these conditions.

1,2-Bis (2,4,6-tribromophenoxy) ethane (BTBPE) has been increasingly detected in environmental and biota samples, primarily accumulating in the liver. However, the mechanism underlying BTBPE-induced metabolic dysregulation remains unclear. In this study, molecular docking and microscale thermophoresis assays indicated that BTBPE binds to zebrafish liver X receptor α (LXRα). Subsequently, zebrafish embryos were exposed to BTBPE, an LXR antagonist (GSK2033), or coexposed to BTBPE with an LXR agonist (GW3965) for 120 h postfertilization (hpf). The results showed that BTBPE induced reduction in body weight and lipid levels, likely via inhibition of the LXR signaling pathway. Exposure of adult female zebrafish to environmentally relevant concentrations of BTBPE (0.01-10 μg/L) for 28 days induced developmental toxicity, evidenced by decreases in body weight, growth rate, and fat accumulation. Metabolomic analysis revealed that BTBPE-induced alterations in liver metabolites were primarily associated with LXR-mediated lipid metabolic pathways such as glycerophospholipid metabolism and primary bile acid biosynthesis. Additionally, BTBPE impaired the physical barrier and induced inflammation, resulting in gut microbiota dysbiosis, which is potentially linked to LXR activation. These effects were validated through the alterations of multiple biomarkers at various levels. Overall, our results suggest that BTBPE disrupts lipid metabolism and gut function via the LXR-mediated pathway.

Mussels are highly efficient filter feeders, playing a crucial role in managing eutrophication and assessing pollution. Although research on nanoplastic (NP) toxicity in marine organisms is expanding, studies on freshwater species remain limited despite freshwater ecosystems being disproportionately biodiverse and vulnerable to pollutants. Here, we quantified the effects of polystyrene nanoplastics (PS-NPs, 50 nm) at concentrations of 0, 2, 20, and 200 μg/L on different growth stages of the freshwater mussel Cristaria plicata. After a 45-day exposure, PS-NPs at concentrations ≥ 20 μg/L damaged intestinal epithelial cilia in both age groups. Exposure to 200 μg/L PS-NPs significantly increased malondialdehyde levels and decreased superoxide dismutase activity in both groups, with adults showing a significant rise in total protein content and juveniles exhibiting marked increases in respiratory and ammonia excretion rates. Additionally, PS-NP exposure significantly altered the relative abundance of gut microbial phyla, including Proteobacteria, Firmicutes, Verrucomicrobiota, and Bacteroidota, with Fusobacteriota also being affected in adults. Juveniles were more sensitive to physiological changes, whereas adults exhibited greater microbiota shifts in response to PS-NP exposure. Therefore, this study provides new insights into the stage-specific effects of PS-NPs on intestinal integrity and physiological and biochemical health in freshwater mussels, underscoring the need for targeted management strategies to protect freshwater ecosystems.

Evidence suggests that increased distal short-chain fatty acid (SCFA) production beneficially impacts metabolic health. However, indigestible carbohydrate availability is limited in the distal colon; consequently, microbes shift toward protein fermentation, often linked to adverse metabolic health effects. We aimed to identify specific fiber(s) that promote saccharolytic fermentation in the distal colon and thereby may (partially) inhibit proteolytic fermentation.

Potato-fiber, pectin, and inulin were studied individually and in combination against a high (predigested) protein background using an in vitro model of the colon (TIM-2) inoculated with pooled, standardized fecal microbiota from individuals with overweight/obesity. Microbiota composition and activity were assessed at different timepoints to simulate the travel throughout the colon (proximal: 0-8 h, distal: 8-24 h) and compared to a high protein (HP)_control, receiving only proteins.

Fiber addition increased total SCFA production compared to HP_control (52.11 ± 1.49 vs 27.07 ± 0.26 mmol) whereas total branched-chain fatty acids (BCFA; a marker for protein fermentation) production only slightly decreased (3.31 ± 0.10 vs 4.18 ± 0.40 mmol). Combining potato-fiber and pectin led to the highest total and distal SCFA production and distal SCFA:BCFA. Fiber addition attenuated HP-induced increases in several bacterial taxa including Mogibacterium and Coprococcus, independent of fiber type. Additionally, time- and fiber-specific microbial signatures were identified: inulin increased Bifidobacterium (proximal) relative abundance and pectin and/or potato-fiber increased Prevotella 9 (distal) relative abundance.

The most marked increase in distal colonic SCFA production was induced by combining potato-fiber and pectin. Further research should elucidate whether this switch toward saccharolytic fermentation translates into beneficial metabolic health effects in humans.

Non-alcoholic fatty liver disease (NAFLD) is a progressive condition with limited effective treatments. This study investigated the therapeutic effects of Aurantio-obtusin (AO), a bioactive compound from Cassiae Semen, on obesity-associated NAFLD. An obesity-related NAFLD model was established in ApoE -/- mice fed a high-fat diet (HFD) for 24 weeks, with AO administered during the last 16 weeks. Mouse body weight, adipose tissue weights, liver weights, serum lipid levels, hepatic steatosis, inflammatory damage, and colonic tissue barrier integrity were evaluated. Gut microbial communities and serum metabolic profiles were analyzed using 16S rRNA sequencing and untargeted metabolomics. Hepatic lipid metabolism-related gene expression was assessed using molecular biology techniques. AO treatment significantly ameliorated HFD-induced adiposity, hyperlipidemia, and NAFLD symptoms. It preserved intestinal barrier integrity, modulated gut microbial composition by enriching beneficial taxa, and improved serum metabolic profiles. AO favorably adjusted hepatic lipid metabolism by upregulating PPARα and CPT1A while downregulating SREBP1, FASN, and SCD1. Correlation analysis revealed significant associations among gut microbial composition, serum metabolites, and disease indicators. AO's therapeutic benefits in NAFLD might be attributed to its ability to modulate gut microbial community composition and serum metabolic profile, enhance intestinal barrier function, and regulate hepatic lipid metabolism gene expression. AO presents a promising therapeutic agent for obesity-associated NAFLD, warranting further investigation into its potential clinical applications.

The purpose of this study is to explore the causal relationship between gut microbiota and gastrointestinal (GI) cancers and to investigate the potential mediating factors influencing the development of GI cancers.

Using data from genome-wide association studies (GWAS), we employed two-sample Mendelian randomization (TSMR) to explore the relationship among gut microbiota, inflammatory cytokines and GI cancers. Subsequently, a multivariable Mendelian randomization (MVMR) analysis was meticulously conducted to perform a mediation analysis, thereby estimating the proportion of mediation effects conferred by inflammatory cytokines.

TSMR analysis established a causal relationship between 23 gut microbiota taxa and 11 inflammatory cytokines with GI cancers. Specifically, 7 gut microbiota taxa were associated with an increased risk of gastric cancer (GC), 6 with small intestine cancer, and 10 with colorectal cancer (CRC). Among the inflammatory cytokines, 4 were linked to GC risk, 3 to small intestine cancer, and to CRC. Mediation analysis further indicatedthat tumor necrosis factor ligand superfamily member 12 (TNFSF12) mediated 9.703% (95% CI 0.108%~15.891%) of the total effect of genus Ruminiclostridium9 on GC.

Our findings support a causal relationship between gut microbiota, inflammatory cytokines, and GI cancers. These biomarkers provide new insights into the mechanisms underlying GI cancers and have the potential to improve strategies forprevention, diagnosis, and treatment.