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Objectives: Dietary strategies to improve arachidonic acid:eicosapentaenoic acid (AA:EPA) ratios are of interest due to potential reductions in inflammation and oxidative stress following exercise. The aim of this study was to investigate the impact of a novel dietary intervention, that is, the ingestion of 30 g of dark chocolate, on blood lipid profiles and gut microbiota composition in elite male soccer players. Methods: Professional male soccer players were randomly assigned to the experimental group (DC) provided with 30 g of dark chocolate or to the control group (WC), provided with 30 g of white chocolate, for 30 days. Before and after intervention, blood, fecal sample, and anthropometry data were collected. For each outcome, two-way repeated-measure analysis of variance was used to identify differences between baseline and endpoint (Week 4), considering treatment (dark chocolate, white chocolate) as intersubjects' factors. Metagenomic analysis was performed following the general guidelines, which relies on the bioBakery computational environment. Results: DC group showed increased plasma polyphenols (from 154.7 ± 18.6 μg gallic acid equivalents/ml to 185.11 ± 57.6 μg gallic acid equivalents/ml, Δ pre vs. post = +30.41 ± 21.50) and significant improvements in lipid profiles: total cholesterol (Δ −32.47 ± 17.18 mg/dl DC vs. Δ −2.84 ± 6.25 mg/dl WC, Time × Treatment interaction p <.001), triglycerides (Δ −6.32 ± 4.96 mg/dl DC vs. Δ −0.42 ± 6.47 mg/dl WC, Time × Treatment interaction p <.001), low-density lipoprotein (Δ −18.42 ± 17.13 mg/dl vs. Δ −2.05 ± 5.19 mg/dl WC, Time × Treatment interaction p <.001), AA/EPA ratio (Δ −5.26 ± 2.35; −54.1% DC vs. Δ −0.47 ± 0.73, −6.41% WC, Time × Treatment interaction p <.001) compared with WC group. In addition, 4 weeks of intervention showed a significant increase in high-density lipoprotein concentration in DC group (Δ + 3.26 ± 4.49 mg/dl DC vs. Δ −0.79 ± 5.12 mg/dl WC). Microbial communities in the DC group maintained a slightly higher microbial stability over time (exhibiting lower within-subject community dissimilarity). Conclusion: Ingesting 30 g of dark chocolate over 4 weeks positively improved AA:EPA ratio and maintained gut microbial stability. Dark chocolate ingestion represents an effective nutritional strategy to improve blood lipid profiles in professional soccer players. What Are the Findings? Ingesting 30 g of dark chocolate for 4 weeks positively influences blood lipid AA: EPA ratio while maintaining gut microbial stability. What This Study Adds? Dietary intake of specific foods such as dark chocolate represents an alternative strategy to support the health and recovery of elite soccer players. WhatImpact Might This Have on Clinical Practice in the Future? From a clinical and translational perspective, dark chocolate ingestion positively modulates favorable blood lipid profiles and polyunsaturated fatty acid metabolism while maintaining gut microbial stability. Dark chocolate ingestion may be considered as an effective nutritional strategy in elite sport environments during periods of high-intensity training and congested competitions. Further research is required to determine functional outcomes associated with the observed improvements in blood lipid profiles. [ABSTRACT FROM AUTHOR]

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a common, yet underdiagnosed, gut condition caused by gut dysbiosis. A previous study has shown the potential of herbal therapy, providing equivalent results to rifaximin. OBJECTIVES: The objective of this study was to assess how the use of an oral botanical regimen may modulate the gut microbiome, facial erythema, and intestinal permeability in those with SIBO. METHODS: This was an open-label prospective study of adults that had lactulose breath test-confirmed SIBO. Participants received a 10-week oral supplementation of a Biocidin liquid tincture and GI Detox+. If participants were found to be non-responsive to treatment after 10 weeks with a persistently positive lactulose breath test, a third oral supplement, Olivirex, was administered for an additional 4 weeks. Lactulose breath tests were administered at baseline, weeks 6, 10, and 14 to assess for SIBO status. A high-resolution photographic analysis system was utilized to analyze changes in facial erythema. Stool sample collections and venipuncture were performed to analyze the gut microbiome and intestinal permeability. RESULTS: A total of 33 subjects were screened with breath testing, and 19 subjects were found to have SIBO. Three of the subjects withdrew during the screening period prior to baseline, and sixteen subjects enrolled. Four subjects dropped out after baseline. Hydrogen-dominant SIBO was the most common subtype of SIBO, followed by methane and hydrogen sulfide. The botanical regimen was most effective for hydrogen- and hydrogen sulfide-dominant SIBO, leading to negative breath test results at week 10 in 42.8% and 66.7% of participants, respectively. Compared to baseline, supplementation with the botanical regimen led to positive shifts in short-chain fatty acid-producing bacteria such as A. muciniphila, F. prausnitzii, C. eutectus, and R. faecis by 31.4%, 35.4%, 24.8%, and 48.7% percent at week 10, respectively. The mean abundance of Firmicutes decreased by 20.2%, Bacteroides increased by 30%, and the F/B ratio decreased by 25.4% at week 10 compared to baseline. At week 10, there was a trending 116% increase in plasma LPS/IgG (p = 0.08). There were no significant changes in plasma zonulin, DAO, histamine, DAO/histamine, LPS/IgG, LPS/IgA, or LPS/IgM. Facial erythema was not statistically different at week 6, but at week 10, there was a 20% decrease (p = 0.001) in redness intensity. Among the patients that extended to week 14, there was no statistical change in erythema. CONCLUSIONS: Supplementation with an antimicrobial botanical supplemental regimen may have therapeutic potential in hydrogen and hydrogen-sulfide subtypes of SIBO. Furthermore, the botanical supplemental regimen may reduce facial erythema, increase SCFA-producing bacteria, decrease the F/B ratio, and modulate markers of intestinal permeability.

PURPOSE: Population-based studies on the associations of plant-based foods, red meat or dairy with gut microbiome are scarce. We examined whether the consumption of plant-based foods (vegetables, potatoes, fruits, cereals), red and processed meat (RPM) or dairy (fermented milk, cheese, other dairy products) are related to gut microbiome in Finnish adults. METHODS: We utilized data from the National FINRISK/FINDIET 2002 Study (n = 1273, aged 25-64 years, 55% women). Diet was assessed with 48-hour dietary recalls. Gut microbiome was analyzed using shallow shotgun sequencing. We applied multivariate analyses with linear models and permutational ANOVAs adjusted for relevant confounders. RESULTS: Fruit consumption was positively (beta = 0.03, SE = 0.01, P = 0.04), while a dairy subgroup including milk, cream and ice-creams was inversely associated (beta=-0.03, SE 0.01, P = 0.02) with intra-individual gut microbiome diversity (alpha-diversity). Plant-based foods (R2 = 0.001, P = 0.03) and dairy (R2 = 0.002, P = 0.01) but not RPM (R2 = 0.001, P = 0.38) contributed to the compositional differences in gut microbiome (beta-diversity). Plant-based foods were associated with several butyrate producers/cellulolytic species including Roseburia hominis. RPM associations included an inverse association with R. hominis. Dairy was positively associated with several lactic producing/probiotic species including Lactobacillus delbrueckii and potentially opportunistic pathogens including Citrobacter freundii. Dairy, fermented milk, vegetables, and cereals were associated with specific microbial functions. CONCLUSION: Our results suggest a potential association between plant-based foods and dairy or their subgroups with microbial diversity measures. Furthermore, our findings indicated that all the food groups were associated with distinct overall microbial community compositions. Plant-based food consumption particularly was associated with a larger number of putative beneficial species.

The insights into interactions between host genetics and gut microbiome (GM) in colorectal tumor susceptibility (CTS) remains lacking. We used Collaborative Cross mouse population model to identify genetic and microbial determinants of Azoxymethane-induced CTS. We identified 4417 CTS-associated single nucleotide polymorphisms (SNPs) containing 334 genes that were transcriptionally altered in human colorectal cancers (CRCs) and consistently clustered independent human CRC cohorts into two subgroups with different prognosis. We discovered a set of genera in early-life associated with CTS and defined a 16-genus signature that accurately predicted CTS, the majority of which were correlated with human CRCs. We identified 547 SNPs associated with abundances of these genera. Mediation analysis revealed GM as mediators partially exerting the effect of SNP UNC3869242 within Duox2 on CTS. Intestine cell-specific depletion of Duox2 altered GM composition and contribution of Duox2 depletion to CTS was significantly influenced by GM. Our findings provide potential novel targets for personalized CRC prevention and treatment.

Bile acids (BA) are among the most abundant metabolites produced by the gut microbiome. Primary BAs produced in the liver are converted by gut bacterial 7-α-dehydroxylation into secondary BAs, which can differentially regulate host health via signaling based on their varying affinity for BA receptors. Despite the importance of secondary BAs in host health, the regulation of 7-α-dehydroxylation and the role of diet in modulating this process is incompletely defined. Understanding this process could lead to dietary guidelines that beneficially shift BA metabolism. Dietary fiber regulates gut microbial composition and metabolite production. We tested the hypothesis that feeding mice a diet rich in a fermentable dietary fiber, resistant starch (RS), would alter gut bacterial BA metabolism. Male and female wild-type mice were fed a diet supplemented with RS or an isocaloric control diet (IC). Metabolic parameters were similar between groups. RS supplementation increased gut luminal deoxycholic acid (DCA) abundance. However, gut luminal cholic acid (CA) abundance, the substrate for 7-α-dehydroxylation in DCA production, was unaltered by RS. Further, RS supplementation did not change the mRNA expression of hepatic BA producing enzymes or ileal BA transporters. Metagenomic assessment of gut bacterial composition revealed no change in the relative abundance of bacteria known to perform 7-α-dehydroxylation. P. ginsenosidimutans and P. multiformis were positively correlated with gut luminal DCA abundance and increased in response to RS supplementation. These data demonstrate that RS supplementation enriches gut luminal DCA abundance without increasing the relative abundance of bacteria known to perform 7-α-dehydroxylation.

BackgroundGut microbes produce short-chain fatty acids (SCFAs), which are associated with broad health benefits. However, it is not fully known how diet and/or the gut microbiome could be modulated to improve SCFA production.ObjectivesThe objective of this study was to identify dietary, inflammatory, and/or microbiome predictors of SCFAs in a cohort of healthy adults.MethodsSCFAs were measured in fecal and plasma samples from 359 healthy adults in the United States Department of Agriculture Nutritional Phenotyping Study. Habitual and recent diet was assessed using a food frequency questionnaire and automated self-administered 24-h dietary assessment tool dietary recalls. Markers of systemic and gut inflammation were measured in fecal and plasma samples. The gut microbiome was assessed using shotgun metagenomics. Using statistics and machine learning, we determined how the abundance and composition of SCFAs varied with measures of diet, inflammation, and the gut microbiome.ResultsWe show that fecal pH may be a good proxy for fecal SCFA abundance. A higher healthy eating index for a habitual diet was associated with a compositional increase in fecal butyrate relative to acetate and propionate. SCFAs were associated with markers of subclinical gastrointestinal (GI) inflammation. Fecal SCFA abundance was inversely related to plasma lipopolysaccharide-binding protein. When we analyzed hierarchically organized diet and microbiome data with taxonomy-aware algorithms, we observed that diet and microbiome features were far more predictive of fecal SCFA abundances compared to plasma SCFA abundances. The top diet and microbiome predictors of fecal butyrate included potatoes and the thiamine biosynthesis pathway, respectively.ConclusionsThese results suggest that resistant starch in the form of potatoes and microbially produced thiamine provide a substrate and essential cofactor, respectively, for butyrate synthesis. Thiamine may be a rate-limiting nutrient for butyrate production in adults. Overall, these findings illustrate the complex biology underpinning SCFA production in the gut. This trial was registered at clinicaltrials.gov as NCT02367287.

Host–microbiota interactions play a critical role in the hosts’ biology, and thus, it is crucial to elucidate the mechanisms that shape gut microbial communities. We leveraged threespine stickleback fish ( Gasterosteus aculeatus ) as a model system to investigate the contribution of host and environmental factors to gut microbiota variation. These fish offer a unique opportunity for experiments in naturalistic conditions; we reared benthic and limnetic ecotypes from three different lakes in experimental ponds, allowing us to assess the relative effects of shared environment (pond), geographic origin (lake-of-origin), trophic ecology and genetics (ecotype) and biological sex on gut microbiota α- and β-diversity. Host ecotype had the strongest influence on α-diversity, with benthic fish exhibiting higher diversity than limnetic fish, followed by the rearing environment. β-diversity was primarily shaped by rearing environment, followed by host ecotype, indicating that environmental factors play a crucial role in determining gut microbiota composition. Furthermore, numerous bacterial orders were differentially abundant across ponds, underlining the substantial contribution of environmental factors to gut microbiota variation. Our study illustrates the complex interplay between environmental and host ecological or genetic factors in shaping the stickleback gut microbiota and highlights the value of experiments conducted under naturalistic conditions for understanding gut microbiota dynamics.

Purpose: To investigate the possible antimicrobial activity of glycine air polishing by comparing peri-implant microbiota before and after treatment. Materials and Methods: A total of 15 patients who received implant-supported full-arch fixed rehabilitations were included. After prosthesis removal (T0), Plaque Index (PI), probing depth (PD), and bleeding on probing (BOP) were recorded. In each hemiarch, the implant with the highest PD score was selected for microbiologic sample collection from the peri-implant sulcus (T0). All patients received two different hygienic protocols (randomly administered, one per each hemiarch): glycine air-polishing (G) and cleansing with cotton pellets soaked in saline (C). At 7 days (T1) and 3 months (T2) after the intervention, PI and BOP were recorded, and new microbiologic samples were taken. Traditional polymerase chain reaction (PCR) and quantitative PCR real-time were employed for microbiologic analysis to investigate how the presence of different bacterial species varied according to the hygienic treatment performed. Results: Treatment G provided a significantly higher PI score reduction around implants compared to treatment C (P = .015). No statistical difference was found in the microbial population around G and C implant sites, with Tannerella forsythia being the most commonly detected bacterial species in both G and C groups. No statistical differences were found between the antimicrobial activity of treatments C and G. Conclusions: Glycine powder air polishing is a valid method for professional hygienic care of implants and was more effective in PI reduction compared to the control treatment. However, its antimicrobial efficacy cannot be confirmed by the outcomes of the present study. [ABSTRACT FROM AUTHOR]

The movement of organic anionic drugs across cell membranes is partly governed by interactions with SLC and ABC transporters in the intestine, liver, kidney, blood-brain barrier, placenta, breast, and other tissues. Major transporters involved include organic anion transporters (OATs, SLC22 family), organic anion transporting polypeptides (OATPs, SLCO family), and multidrug resistance proteins (MRPs, ABCC family). However, the sets of molecular properties of drugs that are necessary for interactions with OATs (OAT1, OAT3) vs. OATPs (OATP1B1, OATP1B3) vs. MRPs (MRP2, MRP4) are not well-understood. Defining these molecular properties is necessary for a better understanding of drug and metabolite handling across the gut-liver-kidney axis, gut-brain axis, and other multi-organ axes. It is also useful for tissue targeting of small molecule drugs and predicting drug-drug interactions and drug-metabolite interactions. Here, we curated a database of drugs shown to interact with these transporters in vitro and used chemoinformatic approaches to describe their molecular properties. We then sought to define sets of molecular properties that distinguish drugs interacting with OATs, OATPs, and MRPs in binary classifications using machine learning and artificial intelligence approaches. We identified sets of key molecular properties (e.g., rotatable bond count, lipophilicity, number of ringed structures) for classifying OATs vs. MRPs and OATs vs. OATPs. However, sets of molecular properties differentiating OATP vs. MRP substrates were less evident, as drugs interacting with MRP2 and MRP4 do not form a tight group owing to differing hydrophobicity and molecular complexity for interactions with the two transporters. If the results also hold for endogenous metabolites, they may deepen our knowledge of organ crosstalk, as described in the Remote Sensing and Signaling Theory. The results also provide a molecular basis for understanding how small organic molecules differentially interact with OATs, OATPs, and MRPs.

The complex role of the gut microbiome in the pathogenesis of gastrointestinal (GI) disorders is an emerging area of research, and there is considerable interest in understanding how diet can alter the composition and function of the microbiome. Prebiotics and probiotics have been shown to beneficially modulate the gut microbiome, which underlies their potential for benefit in GI conditions. Formulating specific recommendations for the public regarding these dietary supplements has been difficult due to the significant heterogeneity between strains, doses, and duration of treatment investigated across studies, as well as safety concerns with administering live organisms. This review aims to summarize the existing evidence for the use of prebiotics and probiotics in various GI disorders, paying special attention to strain-specific effects that emerged and any adverse effects noted.

BackgroundOrganophosphorus pesticides (OP) have been associated with various human health conditions. Animal experiments and in-vitro models suggested that OP may also affect the gut microbiota. We examined associations between ambient chronic exposure to OP and gut microbial changes in humans.MethodsWe recruited 190 participants from a community-based epidemiologic study of Parkinson's disease living in a region known for heavy agricultural pesticide use in California. Of these, 61% of participants had Parkinson's disease and their mean age was 72 years. Microbiome and predicted metagenome data were generated by 16S rRNA gene sequencing of fecal samples. Ambient long-term OP exposures were assessed using pesticide application records combined with residential addresses in a geographic information system. We examined gut microbiome differences due to OP exposures, specifically differences in microbial diversity based on the Shannon index and Bray-Curtis dissimilarities, and differential taxa abundance and predicted Metacyc pathway expression relying on regression models and adjusting for potential confounders.ResultsOP exposure was not associated with alpha or beta diversity of the gut microbiome. However, the predicted metagenome was sparser and less evenly expressed among those highly exposed to OP (p = 0.04). Additionally, we found that the abundance of two bacterial families, 22 genera, and the predicted expression of 34 Metacyc pathways were associated with long-term OP exposure. These pathways included perturbed processes related to cellular respiration, increased biosynthesis and degradation of compounds related to bacterial wall structure, increased biosynthesis of RNA/DNA precursors, and decreased synthesis of Vitamin B1 and B6.ConclusionIn support of previous animal studies and in-vitro findings, our results suggest that ambient chronic OP pesticide exposure alters gut microbiome composition and its predicted metabolism in humans.

IntroductionPolycystic ovary syndrome (PCOS) is a common endocrine pathology in women. In addition to infertility, women with PCOS have metabolic dysregulation which predisposes them to Type 2 diabetes, cardiovascular disease and non-alcoholic fatty liver disease. Moreover, women with PCOS have changes in their gut microbial community that may be indicative of dysbiosis. While hyperandrogenism is associated with both the development of metabolic dysfunction and gut dysbiosis in females, the mechanisms involved are not well understood.MethodsWe used dihydrotestosterone (DHT) and ovariectomy (OVX) mouse models coupled with metabolic assessments and 16S rRNA gene sequencing to explore the contributions of hyperandrogenism and oestrogen deficiency to the development of insulin resistance and gut microbial dysbiosis in pubertal female mice.ResultsWe demonstrated that, while DHT treatment or OVX alone were insufficient to induce insulin resistance during the pubertal-to-adult transition, combining OVX with DHT resulted in insulin resistance similar to that observed in letrozole-treated mice with elevated testosterone and decreased oestrogen levels. In addition, our results showed that OVX and DHT in combination resulted in a distinct shift in the gut microbiome compared to DHT or OVX alone, suggesting that the substantial metabolic dysregulation occurring in the OVX + DHT model was accompanied by unique changes in the abundances of gut bacteria including S24-7, Rikenellaceae and Mucispirillum schaedleri.ConclusionsWhile hyperandrogenism plays an important role in the development of metabolic dysregulation in female mice, our results indicate that investigation into additional factors influencing insulin resistance and the gut microbiome during the pubertal-to-adult transition could provide additional insight into the pathophysiology of PCOS.

Chemotherapy is used as neoadjuvant therapy for all subgroups of breast cancer, including ER-positive, and HER2-negative cases. However, studies have suggested that using aromatase inhibitors combined with CDK4/6-inhibitors might be an appropriate alternative in selected patients. Thus, the NEOLETRIB trial evaluates the response of ER-positive, HER2-negative luminal A/B breast cancer to the combination of letrozole and ribociclib in the neoadjuvant setting. Comprehensive molecular biology procedures, including sequential single-cell RNA-sequencing of tumor biopsies, are performed during 6 months of treatment with extensive biobanking of blood samples, tumor biopsies and gut microbiome specimens. Our findings will hopefully contribute to an improved selection of patients who may benefit from this drug combination and give new insights into the intra-tumoral changes during this treatment. Trial registration number:NCT05163106 (ClinicalTrials.gov) Article highlights Background & rationale Hormone receptor-positive breast cancer is the most common subtype and accounts for about 70–80% of all breast cancer patients. The rationale for using neoadjuvant therapy in the treatment of early breast cancer is to down-size large, otherwise inoperable tumors, with or without axillary lymph node metastasis, before definite surgery. Chemotherapy is still widely used as neoadjuvant therapy for all subgroups of breast cancer, including ER-positive, and HER2-negative cases. Neoadjuvant endocrine treatment with aromatase inhibitors and a CDK4/6 inhibitor in combination is currently tested in the neoadjuvant setting with promising results. Trial design The NEOLETRIB trial is a Phase-II, multicenter, single-arm, open-label, neoadjuvant trial. Objectives The trial aims to comprehensively study the tumor response to the highly potent drug combination of letrozole and ribociclib in women with locally advanced, ER-positive, luminal A/B breast cancer. In premenopausal women, goserelin will be added to letrozole and ribociclib. Comprehensive molecular biology procedures, including sequential single-cell RNA-sequencing of tumor biopsies, are performed during 6 months of treatment with extensive biobanking of blood samples, tumor biopsies and gut microbiome specimens. Conclusion The findings will hopefully contribute to an improved selection of patients who may benefit from this drug combination, and give new insights into the intra-tumoral changes during this treatment. [ABSTRACT FROM AUTHOR]

Phenolic compounds show promise in treating obesity and enhancing intestinal health. This systematic review addressed the following question: "What are the effects of polyphenols on intestinal health in preclinical studies with diet-induced obesity?". The review followed PRISMA guidelines and was registered in PROSPERO(CRD42021262445). Studies published until April 2024 were selected from Medline(PubMed), Web of Science, Scopus, Embase, and ScienceDirect using terms related to polyphenols, obesity, and microbiota in rats and mice. Thirty papers meeting PICOS criteria were included. Bias risk was assessed with the SYRCLE tool, yielding scores between 4.5 and 7.0 out of 10. Findings indicated that 22 phenolic compounds improved gut microbiota diversity, reduced the Firmicutes/Bacteroides ratio, and modulated microbiota at various taxonomic levels. They also increased short-chain fatty acids, tight-junction expression, enhanced intestinal morphology, and reduced endotoxemia and inflammatory cytokines. These results suggest phenolic compounds may help treat obesity by modifying the microbiota and improving intestinal health. However, further research is needed to standardize data and facilitate meta-analyses. [ABSTRACT FROM AUTHOR]

Existence of Trimethylamine N-oxide (TMAO) and trimethylamine (TMA) are well recognized through our multiple human activities. Most of them are derived from quaternary ammoniums widely distributed in natural products, which have N-trimethyl moiety. There could also be some inhibitors to reduce their yield. TMAO is known as a representative component in seafood and is recently gaining large attention. TMAO is formed mostly from choline and carnitine in animal products by mediating gut microbes and host monooxygenase in the human body. Teleost tilapia also has a similar mechanism well mediating choline. In marine habitants, TMAO is utilized as an osmolyte. In human, however, the endogenous TMAO is reported to be associated with a risk of cardiovascular events. During the organic evolution, marine creatures could develop utilizing TMAO while avoiding risks. This article, therefore, reviews and characterize the TMAO/TMA having different profiles, and consider the possible inhibitors preventing undesired metabolisms, to try to find clues of the TMAO subjects and consider possibilities and prospects. [ABSTRACT FROM AUTHOR]

Importance: Obstructive sleep apnea (OSA) in children is linked with alterations in the gut microbiome. The influence of adenotonsillectomy (AT), a primary intervention for OSA, on gut microbiota dynamics relative to disease severity remains to be elucidated. Objective: This study aimed to investigate the impact of OSA severity and AT on the gut microbiome in pediatric patients. Design: A prospective observational study. Setting: Tertiary referral center. Participants: A cohort of 55 pediatric patients treated with AT for OSA. Intervention: Total tonsillectomy and adenoidectomy procedures. Main Outcome Measures: Comprehensive evaluations included in-laboratory polysomnography and 16S rRNA gut microbiome profiling at baseline, and again at 3rd and 12thmonth following surgery. Results: Initial findings showed uniform α-diversity across different severities of OSA, while β-diversity was significantly elevated in the severe OSA subgroup. Certain gut microbiota taxa (Lachnospiraceae NK4A136 group, Ruminococcaceae UCG-002, Ruminococcaceae UCG-014, Alloprevotella, Christensenellaceae R-7 group, Ruminococcaceae UCG-005, Lactobacillus murinus, and Prevotella nigrescens) were found to inversely correlate with the apnea-hypopnea index (AHI). Significant post-AT improvements in AHI and other polysomnographic metrics were observed. Notably, AHI changes post-AT were positively associated with microbial α-diversity (species richness), β-diversity, and specific bacterial taxa (Enterobacter, Parasutterella, Akkermansia, Roseburia, and Bacteroides plebeius DSM 17135), but negatively with other taxa (Fusicatenibacter, Bifidobacterium, UBA1819, Ruminococcus gnavus group, Bifidobacterium longum subsp. Longum, and Parabacteroides distasonis) and specific metabolic pathways (purine metabolism, transcription factors, and type II diabetes mellitus). The postoperative patterns of α- and β-diversity mirrored baseline values. Conclusions and Relevance: This study documents significant changes in the gut microbiome of pediatric patients after AT, including variations in α- and β-diversities, bacterial communities, and inferred metabolic functions. These changes suggest a potential association between the surgical intervention and microbiome alterations, although further studies are necessary to discern the specific contributions of AT amidst possible confounding factors such as antibiotic use. [ABSTRACT FROM AUTHOR]

Objective: The influence of different faecal collection methods on metagenomic analyses remains under discussion, and there is no general agreement on which collection method is preferable for gut microbiome research. We compared faecal samples collected in tubes without preservatives with those containing 10 mL of 96% ethanol for gut microbiome research when the timeframe from defecation to freezing at – 80 °C was up to 24 h. We aimed to compare the collection methods on faeces from participants with inflammatory and non-inflammatory gastrointestinal disorders and healthy controls to investigate the most suitable method when considering data yield, human fraction of sequencing reads, and ease of use. We also examined the faecal sample homogeneity. Results: Faeces collected in tubes without preservatives resulted in more sequencing reads compared to faeces collected in tubes with 96% ethanol and were also easier to handle. The human fraction of total reads in faeces collected in ethanol from participants with inflammatory bowel disease was higher than all other samples. DNA extraction and sequencing from two different locations in the same faecal sample gave similar results and showed sample homogeneity. [ABSTRACT FROM AUTHOR]

Gut microbiota is considered a key player modulating the response to immune checkpoint inhibitors (ICI) in cancer. The effects of dietary pattern on this interaction is not well-studied. A prospective multicenter cohort of 95 patients with advanced non-small cell lung cancer (NSCLC) undergoing ICI therapy were enrolled. Stool shotgun metagenomic sequencing was performed. Three-day dietary patterns before ICI were assessed. Patients were categorized as hyperprogressive disease (HPD) if they exhibited a time to treatment failure of less than 2 months. All others were categorized as non-hyperprogressive disease (non-HPD). The correlation between dietary patterns, gut microbiome, and response to ICI therapy was analyzed. In the multivariate analysis, a high abundance of Firmicutes unclassified and the Ruminococcaceae family correlated with a significantly diminished progression-free survival (PFS) with an HR of 2.40 [P = 0.006] and 4.30 [P = 0.005], respectively. More specifically, within the subset of NSCLC patients treated solely with ICI therapy, a high abundance of Intestinimonas and the Enterobacteriaceae family were associated with substantially reduced PFS with an HR of 2.61 [P = 0.02] and HR 3.34 [P = 0.005], respectively. In our comprehensive dietary pattern analysis, the HPD group showed increased consumption of cholesterol, sodium, and fats beyond recommended levels compared to the non-HPD group. This group also displayed a tendency towards higher food pattern scores characterized by a high intake of fat and dairy products. Our study revealed a distinct association between the gut microbiome composition and treatment outcomes. The overall composition of diet might be related to ICI therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Berries represent an important source of bioactive compounds, among which, (poly)phenols are the main constituents. (Poly)phenols have been shown to have important biological activities and in particular, to take a relevant role in mediating the modulation of gut microbiota and human health. Gut microbiota constitute significant players in the metabolism of ingested (poly)phenols and consequently in their biological effects. However, the evidence regarding the mutual contribution between (poly)phenol intake and gut microbiota activity in humans is still unclear. The aim of the current systematic review was to collect and assess results from randomized clinical trials addressing the role of berries in the modulation of the gut microbiota composition and how this can contribute to the metabolism of berry (poly)phenols. When information was available, the interaction of berry-gut microbiota on human health was evaluated. A total of 16 trials were included and analyzed. Overall, berries and their (poly)phenols could represent a driver for the modulation of intestinal microbes. The gut microbiota catabolize (poly)phenols by producing bioactive metabolites which can positively affect both the composition of commensal microbiota and also the host health. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal symptoms are now detected early in the clinical course of many dementia patients, and studies of the microbiome-gut-brain axis have confirmed bidirectional interactions between the gut and the brain. However, the causal relationship between gut microbiota and cognitive impairment has not been fully established. Therefore, this study conducted a bidirectional Mendelian randomization study to elucidate the potential causal relationship of gut microbiota to cognitive impairment. Objective: Using Mendelian randomization to identify gut flora with a genetic causal effect on the development of cognitive impairment. Methods: This study utilized publicly available genome-wide association study summary data to perform MR analysis, with gut microbiota as the exposure and various cognitive function indicators as well as scores for Alzheimer's disease as outcomes. This study selected single nucleotide polymorphisms as instrumental variables based on p-values, F-statistics, and r2. Bidirectional Mendelian randomization was conducted using methods such as inverse variance weighted, MR-Egger, simple mode, and weighted mode to assess the causal relationship. Concurrently, this study carried out Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis to identify potential heterogeneity and horizontal pleiotropy. Results: This study identified a total of 31 gut microbes that have a causal relationship with cognitive impairment, which include 1 phylum, 4 classes, 3 orders, 2 families, and 21 genera. Conclusions: This study unveiled specific gut microbiota associated with cognitive impairment, offering new insights and approaches for the prevention and treatment of cognitive impairment through gut microbiota such as Bifidobacterium and Ruminococcus gnavus group. [ABSTRACT FROM AUTHOR]

Background and Purpose: Antipsychotics such as olanzapine are associated with significant metabolic dysfunction, attributed to gut microbiome dysbiosis. A recent notion that most psychotropics are detrimental to the gut microbiome has arisen from consistent findings of metabolic adverse effects. However, unlike olanzapine, the metabolic effects of lurasidone are conflicting. Thus, this study investigates the contrasting effects of olanzapine and lurasidone on the gut microbiome to explore the hypothesis of 'gut neutrality' for lurasidone exposure. Experimental Approach: Using Sprague–Dawley rats, the effects of olanzapine and lurasidone on the gut microbiome were explored. Faecal and blood samples were collected weekly over a 21‐day period to analyse changes to the gut microbiome and related metabolic markers. Key Results: Lurasidone triggered no significant weight gain or metabolic alterations, instead positively modulating the gut microbiome through increases in mean operational taxonomical units (OTUs) and alpha diversity. This novel finding suggests an underlying mechanism for lurasidone's metabolic inertia. In contrast, olanzapine triggered a statistically significant decrease in mean OTUs, substantial compositional variation and a depletion in short‐chain fatty acid abundance. Microbiome depletion correlated with metabolic dysfunction, producing a 30% increase in weight gain, increased pro‐inflammatory cytokine expression, and increased blood glycaemic and triglyceride levels. Conclusion and Implications: Our results challenge the notion that all antipsychotics disrupt the gut microbiome similarly and highlights the potential benefits of gut‐neutral antipsychotics, such as lurasidone, in managing metabolic side effects. Further research is warranted to validate these findings in humans to guide personalised pharmacological treatment regimens for schizophrenia. [ABSTRACT FROM AUTHOR]

The human gut microbiota plays numerous roles in regulating host growth, the immune system, and metabolism. Age-related changes in the gut environment lead to chronic inflammation, metabolic dysfunction, and illness, which in turn affect aging and increase the risk of neurodegenerative disorders. Local immunity is also affected by changes in the gut environment. Polyamines are crucial for cell development, proliferation, and tissue regeneration. They regulate enzyme activity, bind to and stabilize DNA and RNA, have antioxidative properties, and are necessary for the control of translation. All living organisms contain the natural polyamine spermidine, which has anti-inflammatory and antioxidant properties. It can regulate protein expression, prolong life, and improve mitochondrial metabolic activity and respiration. Spermidine levels experience an age-related decrease, and the development of age-related diseases is correlated with decreased endogenous spermidine concentrations. As more than just a consequence, this review explores the connection between polyamine metabolism and aging and identifies advantageous bacteria for anti-aging and metabolites they produce. Further research is being conducted on probiotics and prebiotics that support the uptake and ingestion of spermidine from food extracts or stimulate the production of polyamines by gut microbiota. This provides a successful strategy to increase spermidine levels. [ABSTRACT FROM AUTHOR]

Human milk oligosaccharides (HMOs) have attracted considerable attention owing to their unique physiological functions. Two important tetrasaccharides, lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT), are core structures of HMOs. Their safety has been evaluated and they can be added to infant formula as functional ingredients. The fucosylated derivatives of LNT and LNnT, mainly lacto-N-fucopentaose (LNFP) I, LNFP II, LNFP III, and lacto-N-difucohexaose I, exhibit prominent physiological characteristics, including modificating the intestinal microbiota, immunomodulation, anti-bacterial activities, and antiviral infection. However, they have received lesser attention than 2'-fucosyllactose. As precursors, LNT and LNnT are connected to one or two fucosyl units through α1,2/3/4 glycosidic bonds, forming a series of compounds with complex structures. These complex fucosylated oligosaccharides can be biologically synthesized using enzymatic and cell factory approaches. This review summarizes the occurrence, physiological effects, and biosynthesis of fucosylated LNT and LNnT derivatives and their future development. [ABSTRACT FROM AUTHOR]

Oligosaccharides, a low polymerization degree of carbohydrate, possess various physiological activities, such as anti-diabetes, anti-obesity, anti-aging, anti-viral, and gut microbiota regulation, having a widely used in food and medical fields. However, due to the limited natural oligosaccharides, many un-natural oligosaccharides from complex polysaccharides are being studied for amplifying the available pool of oligosaccharides. More recently, various oligosaccharides were developed by using several artificial strategies, such as chemical degradation, enzyme catalysis, and biosynthesis, then they can be applied in various sectors. Moreover, it has gradually become a trend to use biosynthesis to realize the synthesis of oligosaccharides with clear structure. Emerging research has found that un-natural oligosaccharides exert more comprehensive effects against various human diseases through multiple mechanisms. However, these oligosaccharides from various routes have not been critical reviewed and summarized. Therefore, the purpose of this review is to present the various routes of oligosaccharides preparations and healthy effects, with a focus on diabetes, obesity, aging, virus, and gut microbiota. Additionally, the application of multi-omics for these natural and un-natural oligosaccharides has also been discussed. Especially, the multi-omics are needed to apply in various disease models to find out various biomarkers to respond to the dynamic change process of oligosaccharides. [ABSTRACT FROM AUTHOR]

The goal of food allergy (FA) prevention and treatment is to induce oral tolerance (OT). Appropriate nutritional interventions are essential to induce OT to food allergens. This review introduces the mechanism of OT and the importance of early nutritional interventions, and then firstly summarizes specific nutritional factors to induce the development of OT of FA, including proteins, vitamins, fatty acids, saccharides and probiotics. The regulatory mechanism mainly induces the development of tolerance by increasing local or systemic protective regulatory T cells (Tregs) to suppress FA, while the gut microbiota may also be changed to maintain intestinal homeostasis. For allergens-specific OT, the disruption to the structure of proteins and epitopes is critical for the induction of tolerance by hydrolyzed and heated proteins. Vitamins (vitamin A, D), fatty acids, saccharides and probiotics as allergens nonspecific OT also induce the development of OT through immunomodulatory effects. This review contributes to our understanding of OT in FA through nutritional interventions. Nutritional interventions play an important role in the induction of OT, and offer promising approaches to reduce allergy risk and alleviate FA. Moreover, due to the importance and diversity of nutrition, it must be the future trend of induction of OT in FA. [ABSTRACT FROM AUTHOR]

One of the emerging non-digestible oligosaccharide prebiotics is β-mannooligosaccharides (β-MOS). β-MOS are β-mannan derived oligosaccharides, they are selectively fermented by gut microbiota, promoting the growth of beneficial microorganisms (probiotics), whereas the growth of enteric pathogens remains unaffected or gets inhibited in their presence, along with production of metabolites such as short-chain fatty acids. β-MOS also exhibit several other bioactive properties and health-promoting effects. Production of β-MOS using the enzymes such as β-mannanases is the most effective and eco-friendly approach. For the application of β-MOS on a large scale, their production needs to be standardized using low-cost substrates, efficient enzymes and optimization of the production conditions. Moreover, for their application, detailed in-vivo and clinical studies are required. For this, a thorough information of various studies in this regard is needed. The current review provides a comprehensive account of the enzymatic production of β-MOS along with an evaluation of their prebiotic and other bioactive properties. Their characterization, structural-functional relationship and in-vivo studies have also been summarized. Research gaps and future prospects have also been discussed, which will help in conducting further research for the commercialization of β-MOS as prebiotics, functional food ingredients and therapeutic agents. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis explores alterations in the gut microbiota of patients with Multiple Sclerosis (MS) using 16S ribosomal RNA (rRNA) gene sequencing. Methods: Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, our comprehensive review spanned major databases, including PubMed, Web of Science, Embase, Cochrane, and Ovid, targeting observational studies that implemented 16S rRNA gene sequencing on fecal specimens. The quality of these studies was meticulously evaluated using the Newcastle-Ottawa scale. Results: Our search yielded 26 relevant studies conducted between 2015-2022, encompassing 2885 participants. No significant differences were observed in alpha diversity indices (Shannon, Chao1, Operational Taxonomic Units (OTU), and Simpson) between MS patients and controls in general. Nonetheless, subgroup analyses according to disease activity using the Shannon index highlighted a significant decrease in microbial diversity during MS's active phase. Similarly, an evaluation focusing on MS phenotype revealed diminished diversity in individuals with relapsing-remitting MS (RRMS). Microbial composition analysis revealed no consistent increase in pro-inflammatory Bacteroidetes or decrease in anti-inflammatory Firmicutes within the MS cohort. Conclusion: The gut microbiome's role in MS presents a complex panorama, where alterations in microbial composition might hold greater significance to disease mechanisms than diversity changes. The impact of clinical factors such as disease activity and phenotype are moderately significant, underscoring the need for further research to elucidate these relationships. Prospective research should employ longitudinal methodologies to elucidate the chronological interplay among gut microbiota, disease evolution, and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: This research aimed to delineate the pharmacological mechanisms of 7-Hydroxycoumarin (7-HC) on ulcerative colitis (UC) employing network pharmacology and experimental validation. Methods: To investigate the therapeutic effects of 7-HC on UC, a UC mouse model was established through the unrestricted intake of 3.0% dextran sulfate sodium (DSS) in their drinking water. Subsequently, we predicted the core targets and signaling pathways of 7-HC for the treatment of UC using the network pharmacology approach. Finally, the insights gained from network pharmacology were further validated by molecular docking, molecular dynamics simulation as well as in vivo experiments. Results: Administering 7-HC orally to mice with UC led to a marked improvement in colitis indicators. Furthermore, 7-HC significantly lowered the levels of inflammatory cytokines (TNF-α, IL-1β) in the colon and modulated oxidative stress markers (MPO, SOD). Subsequent studies identified 2 core targets (AKT1 and EGFR) in the colon of UC mice that were inhibited by 7-HC. Network pharmacology and experimental validation showed that 7-HC can reduce the expression of MAPK pathway markers P38, JNK, ERK, and their phosphorylation; 7-HC can also ameliorate UC by regulating the gut microbiome. Conclusion: 7-HC demonstrates considerable efficacy in alleviating UC in mice, primarily through substantial diminution of tissue inflammation and oxidative stress. This is the first time that 7-HC has been found to treat UC by inhibiting the MAPK pathway and modulating the gut microbiota, providing a fresh perspective on the pharmacological mechanisms through which 7-HC operates in the management of UC. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota may be involved in neuropathic pain. However, the causal association between gut microbiota and neuropathic pain remains unclear. Whether immune cells and inflammatory factors mediate the pathway from gut microbiota to neuropathic pain has not been elucidated. Methods: We obtained the summary data of 412 gut microbiota, 731 immune cells, 91 inflammatory factors, and five types of neuropathic pain (drug-induced neuropathy, postherpetic neuralgia, sciatica, trigeminal neuralgia, and unspecified neuralgia) from large-scale genome-wide association study (GWAS) datasets and the FinnGen database. We used bidirectional Mendelian randomization (MR) analysis to explore the causal association between gut microbiota and neuropathic pain. Additionally, we conducted a mediation analysis to identify whether immune cells and inflammatory factors act as mediators within these causal relationships. Results: Our study revealed 30 causal relationships between 26 gut bacterial taxa and five types of neuropathic pain, including four associated with drug-induced neuropathy, six with postherpetic neuralgia, five with sciatica, eight with trigeminal neuralgia, and seven with unspecified neuralgia. Moreover, we identified 35 gut bacterial pathway abundances causally involved in neuropathic pain. The reverse MR analysis showed no evidence of reverse causality from gut microbiota to neuropathic pain. Mediation analysis demonstrated that the immune cell phenotype "HLA-DR++ monocyte % leukocyte" mediated the causal relationship between p_Proteobacteria and sciatica with a mediation proportion of 36.15% (P = 0.038), whereas "CD11c on CD62L+ myeloid dendritic cell" mediated the causal pathway from assimilatory sulfate reduction to trigeminal neuralgia with a mediation proportion of 27.90% (P = 0.041). Conclusion: This study identified the causal relationships between several specific gut microbiota and various neuropathic pain subtypes. Additionally, two immune cells may act as potential mediators in the pathways from gut microbiota to neuropathic pain. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion Alterations in gut microbiota are observed in Parkinson's disease (PD). Previous studies on microbiota‐derived metabolites in PD were small‐scale and post‐diagnosis, raising concerns about reverse causality.Our goal was to prospectively investigate the association between plasma microbial metabolites and PD risk within a metabolomics framework.A nested case–control study within the prospective EPIC4PD cohort, measured pre‐diagnostic plasma microbial metabolites using untargeted metabolomics.Thirteen microbial metabolites were identified nominally associated with PD risk (P‐value < 0.05), including amino acids, bile acid, indoles, and hydroxy acid, although none remained significant after multiple testing correction. Three pathways were implicated in PD risk: valine, leucine, and isoleucine degradation, butanoate metabolism, and propanoate metabolism. PD‐associated microbial pathways were more pronounced in men, smokers, and overweight/obese individuals.Changes in microbial metabolites may represent a pre‐diagnostic feature of PD. We observed biologically plausible associations between microbial pathways and PD, potentially influenced by individual characteristics. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

ABSTRACT Comparative approaches in animal gut microbiome research have revealed patterns of phylosymbiosis, dietary and physiological convergences, and environment–host interactions. However, most large‐scale comparative studies, especially those that are highly cited, have focused on mammals, and efforts to integrate comparative approaches with existing ecological frameworks are lacking. While mammals serve as useful model organisms, developing generalised principles of how animal gut microbiomes are shaped and how these microbiomes interact bidirectionally with host ecology and evolution requires a more complete sampling of the animal kingdom. Here, we provide an overview of what past comparative studies have taught us about the gut microbiome, and how community ecology theory may help resolve certain contradictions in comparative gut microbiome research. We explore whether certain hypotheses are supported across clades, and how the disproportionate focus on mammals has introduced potential bias into gut microbiome theory. We then introduce a methodological solution by which public gut microbiome data of understudied hosts can be compiled and analysed in a comparative context. Our aggregation and analysis of 179 studies shows that generating data sets with rich host diversity is possible with public data and that key gut microbes associated with mammals are widespread across the animal kingdom. We also show the effects that sample size and taxonomic rank have on comparative gut microbiome studies and that results of multivariate analyses can vary significantly with these two parameters. While challenges remain in developing a universal model of the animal gut microbiome, we show that existing ecological frameworks can help bring us one step closer to integrating the gut microbiome into animal ecology and evolution. [ABSTRACT FROM AUTHOR]

Intratumoral TLR9 agonists and anti-PD-1 produce clinical responses and broad immune activation. We conducted a single-arm study of neoadjuvant TLR9 agonist vidutolimod combined with anti-PD-1 nivolumab in high-risk resectable melanoma. In 31 evaluable patients, 55% major pathologic response (MPR) was observed, meeting primary endpoint. MPR was associated with necrosis, and melanophagocytosis with increased CD8+ tumor-infiltrating lymphocytes and plasmacytoid dendritic cells (pDCs) in the tumor microenvironment, and increased frequencies of Ki67+CD8+ T cells peripherally. MPRs had an enriched pre-treatment gene signature of myeloid cells, and response to therapy was associated with gene signatures of immune cells, pDCs, phagocytosis, and macrophage activation. MPRs gut microbiota were enriched for Gram-negative bacteria belonging to the Bacteroidaceae and Enterobacteriaceae families and the small subgroup of Gram-negative Firmicutes. Our findings support that combined vidutolimod and nivolumab stimulates a broad anti-tumor immune response and is associated with distinct baseline myeloid gene signature and gut microbiota. ClinicalTrials.gov identifier: NCT03618641. [Display omitted] • Neoadjuvant intratumoral vidu/nivo produces pathologic responses in stage III melanoma • Response is linked to myeloid cells, pDCs, and CD8+ T cells within tumor • Responder gut microbiota signatures vidu/nivo are distinct from those in anti-PD-1 Neoadjuvant immunotherapy improves relapse-free survival in stage III melanoma. The novel combination of intratumoral vidu/nivo produces 55% major pathologic response (MPR) with an acceptable safety profile. MPR was associated with intratumoral myeloid cells, pDCs, and CD8+ TIL. Gut microbiota signatures in vidu/nivo MPR are distinct from those in anti-PD-1 responders. [ABSTRACT FROM AUTHOR]

[Display omitted] • MOE ameliorates depressive behaviors by modulating the microbiota-gut-brain axis. • MOE restored sucrose preference in depressed mice. • MOE reversed CUMS-induced 5-HT reduction in the prefrontal cortex and hippocampus. • MOE increased gut lactobacilli in stressed mice. The gut microbiota has been posited as a target for the treatment of major depressive disorder. Herein, we investigated the effect of the hydroethanolic leaf extract of Mallotus oppositifolius (MOE) on the gut microbiota of mice and how this contributes to its known antidepressant-like effect. A 6-week chronic unpredictable mild stress (CUMS) procedure was employed in 7 groups of mice to induce depression. From the third week, oral MOE treatments (10, 30, 100 mg/kg) and two reference drugs, fluoxetine (12 mg/kg) and minocycline (40 mg/kg), known to affect the gut microbiota, were administered. The sixth and seventh groups were the vehicle stressed (VEH-S) and non-stressed groups (VEH-NS). Changes in depressive-like behaviors were assessed using sucrose preference test while the forced swimming test (FST) was used to assess sustained antidepressant-effect after treatment discontinuation. Moreover, changes in prefrontal cortex (PFC) and hippocampal serotonin (5-HT) levels were evaluated using enzyme-linked immunosorbent assay (ELISA). The effect of treatment on the profile of the gut microbiota of the groups was elucidated using 16S rRNA Oxford Nanopore sequencing. MOE and reference drugs reversed the depression-associated reduction in sucrose preference when compared to VEH-S. MOE (with peak effect at 30 mg/kg) reduced immobility while increasing swimming and climbing behaviors. MOE reversed CUMS-induced reduction of 5-HT concentration in PFC and hippocampus. The behavioral effects of MOE were associated with shifts in the gut microbiota of CUMS-exposed mice. The study has provided seminal evidence that MOE ameliorates CUMS-induced depressive symptoms by modulating gut microbiota and increasing brain 5-HT levels. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) improve outcomes in advanced melanoma, but many patients are refractory or experience relapse. The gut microbiota modulates antitumor responses. However, inconsistent baseline predictors point to heterogeneity in responses and inadequacy of cross-sectional data. We followed patients with unresectable melanoma from baseline and during anti-PD-1 therapy, collecting fecal and blood samples that were surveyed for changes in the gut microbiota and immune markers. Varying patient responses were linked to different gut microbiota dynamics during ICI treatment. We select complete responders by their stable microbiota functions and validate them using multiple external cohorts and experimentally. We identify major histocompatibility complex class I (MHC class I)-restricted peptides derived from flagellin-related genes of Lachnospiraceae (FLach) as structural homologs of tumor-associated antigens, detect FLach -reactive CD8+ T cells in complete responders before ICI therapy, and demonstrate that FLach peptides improve antitumor immunity. These findings highlight the prognostic value of microbial functions and therapeutic potential of tumor-mimicking microbial peptides. [Display omitted] • Microbiome dynamic during immunotherapy correlates with clinical response in melanoma • Stable microbial functions carried by responders hold cross-cohort prognostic value • MHC class I peptides from stable flagellin-related genes mimic tumor-associated antigens • They induce reactivity on PBMC and TIL from responders and improve antitumor immunity Macandog et al. utilized longitudinal data to identify key gut microbial features in immunotherapy-responsive patients with melanoma. Functions stably carried by responders are specific to gut commensals that reportedly evolved mechanisms for human tolerance. These functions could provide advantage during immunotherapy by mimicking tumor antigens that stimulate effective tumor-clearing immunity. [ABSTRACT FROM AUTHOR]

Background: The gut microbiome modulates the effects of diet on host health, but it remains unclear which specific foods and microbial features interact to influence risk of depression. To understand this interplay, we leveraged decades of dietary and depression data from a longitudinal cohort of women (n = 32,427), along with fecal metagenomics and plasma metabolomics from a substudy (n = 207) nested in this cohort, as well as an independent validation cohort of men (n = 307). Results: We report that citrus intake and its components are prospectively associated with a lower risk of depression and altered abundance of 15 gut microbial species, including enriched Faecalibacterium prausnitzii. In turn, we found a lower abundance of F. prausnitzii and its metabolic pathway, S-adenosyl-L-methionine (SAM) cycle I in participants with depression. To explore causality, we found that lower SAM production by F. prausnitzii may decrease intestinal monoamine oxidase A gene expression implicated in serotonin and dopamine synthesis. Conclusions: These data underscore the role of diet in the prevention of depression and offer a plausible explanation for how the intestinal microbiome modulates the influence of citrus on mental health. ELPzvN5keGYhLtpEkepcja Video Abstract [ABSTRACT FROM AUTHOR]

The animal gut microbiome acts as a crucial link between the host and its environment, playing a vital role in digestion, metabolism, physiology, and fitness. Using 16S rRNA metabarcoding, we investigated the effect of altitude on the microbiome composition of Anatolian Blind Mole Rats (Nannospalax xanthodon) across six locations and three altitudinal groups. We also factored in the host diet, as well as host microsatellite genotypes and thyroid hormone levels. The altitude had a major effect on microbiome composition, with notable differences in the relative abundance of several bacterial taxa across elevations. Contrary to prior research, we found no significant difference in strictly anaerobic bacteria abundance among altitudinal groups, though facultatively anaerobic bacteria were more prevalent at higher altitudes. Microbiome alpha diversity peaked at mid-altitude, comprising elements from both low and high elevations. The beta diversity showed significant association with the altitude. Altitude had a significant effect on the diet composition but not on its alpha diversity. No distinct altitude-related genetic structure was evident among the host populations, and no correlation was revealed between the host genetic relatedness and microbiome composition nor between the host microbiome and the diet. Free thyroxine (FT4) levels increased almost linearly with the altitude but none of the bacterial ASVs were found to be specifically associated with hormone levels. Total thyroxine (TT4) levels correlated positively with microbiome diversity. Although we detected correlation between certain components of the thyroid hormone levels and the microbiome beta diversity, the pattern of their relationship remains inconclusive. [ABSTRACT FROM AUTHOR]

Effects of stress on obesity have been thoroughly studied in high-fat diet fed mice, but not in normal diet fed mice, which is important to clarify because even on a normal diet, some individuals will become obese under stress conditions. Here we compared mice that showed substantial weight gain or loss under chronic mild stress while on a normal diet; we compared the two groups in terms of cognitive function, hypothalamic–pituitary–adrenal signaling, neurogenesis and activation of microglia in hippocampus, gene expression and composition of the gut microbiome. Chronic mild stress induced diet-independent obesity in approximately 20% of animals, and it involved inflammatory responses in peripheral and central nervous system as well as hyperactivation of the hypothalamic–pituitary–adrenal signaling and of microglia in the hippocampus, which were associated with cognitive deficits and impaired hippocampal neurogenesis. It significantly increased in relative abundance at the phylum level (Firmicutes), at the family level (Prevotellaceae ucg − 001 and Lachnospiraceae NK4a136), at the genus level (Dubosiella and Turicibacter) for some enteric flora, while reducing the relative abundance at the family level (Lactobacillaceae and Erysipelotrichaceae), at the genus level (Bacteroidota, Alistipes, Alloprevotella, Bifidobacterium and Desulfovibrio) for some enteric flora. These results suggest that stress, independently of diet, can induce obesity and cognitive decline that involve dysfunctional gut microbiota. These insights imply that mitigation of hypothalamic–pituitary–adrenal signaling and microglial activation as well as remodeling of gut microbiota may reverse stress-induced obesity and associated cognitive decline. [ABSTRACT FROM AUTHOR]

Objective: Chronic migraine (CM) patients with medication overuse headache (MOH) were recently shown to be associated with leaky gut and inflammation. We aimed to investigate gut microbiota profiles of CM patients with MOH, and their correlations with inflammatory serum parameters, migraine food triggers, and comorbid anxiety and depression. Materials and methods: The study included women participants (32 CM patients with NSAID overuse headache, and 16 healthy non-headache sufferers). Migraine duration, monthly migraine headache days, presence of irritable bowel syndrome symptoms, and HADS-D and HADS-A scores were recorded. Serum samples were collected to measure circulating LPS, HMGB1, HIF-1α, and IL-6. The gut microbiota profiles of the patients were evaluated using fecal samples. Results: Serum LPS, HMGB1, HIF-1α, and IL-6 levels were significantly higher in the CM + MOH group compared to the healthy controls. HADS-A and HADS-D scores were considerably higher in the CM + MOH group compared to the healthy controls. In the microbiota analysis, alpha and beta diversities were similar between the two groups. The class Clostridia, the order Eubacteriales, and the genus Ruminococcus were less abundant in the CM + NSAID overuse headache group compared to the control group. At the genus level Desulfovibrio, Gemmiger, and Dialister and at the species level, Clostridium fessum, Blautia luti, Dorea longicatena, Eubacterium coprostanoligenes, and Gemmiger formicilis were more abundant in the CM + NSAID overuse headache group compared to the control group. Desulfovibrio, Gemmiger, Dialister, Ethanoligenens harbinense, Eubacterium coprostanoligenes, Dorea longicatena, and Thermoclostridium stercorarium showed positive correlations and Clostridia bacteria showed negative correlations with migraine food triggers. Positive correlations were found between LPS and Hapalosiphonaceae, HMGB1 and Melghirimyces, HIF1-α and Rouxeilla and Blautia luti, IL-6 and Melghirimyces and Ruminococcus. Conclusion: In CM patients with MOH, we have revealed the presence of dysbiosis towards an inflammatory state, and positive correlations were shown between altered gut microbiota and inflammatory serum parameters and migraine food triggers. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) poses a significant and growing global health challenge, affecting both humans and domestic cats. Research on feline IBD has not kept pace with its widespread prevalence in human populations. This study aimed to develop a model of feline IBD by incorporating dextran sulfate sodium (DSS) to evaluate the therapeutic potential of MSCs and to elucidate the mechanisms that enhance their action. Methods: We conducted a comprehensive clinical assessment, including magnetic resonance imaging (MRI), endoscopy, and histopathological examination. Additionally, alterations in intestinal microbiota were characterized by 16 S rDNA sequencing, and the influence of MSCs on IBD-related gene expression was investigated through transcriptome analysis. Results: According to our findings, MSC treatment significantly mitigated DSS-induced clinical manifestations, reduced inflammatory cell infiltration, decreased the production of inflammatory mediators, and promoted mucosal repair. Regarding the intestinal microbiota, MSC intervention effectively corrected the DSS-induced dysbiosis, increasing the presence of beneficial bacteria and suppressing the proliferation of harmful bacteria. Transcriptome analysis revealed the ability of MSCs to modulate various inflammatory and immune-related signaling pathways, including cytokine-cytokine receptor interactions, TLR signaling pathways, and NF-κB pathways. Conclusion: The collective findings indicate that MSCs exert multifaceted therapeutic effects on IBD, including the regulation of intestinal microbiota balance, suppression of inflammatory responses, enhancement of intestinal barrier repair, and modulation of immune responses. These insights provide a solid scientific foundation for employing MSCs as an innovative therapeutic strategy for IBD and pave the way for future clinical explorations. [ABSTRACT FROM AUTHOR]

Background: Phenotypic age (PhenoAge), a widely used marker of biological aging, has been shown to be a robust predictor of all-cause mortality and morbidity in different populations. Existing studies on biological aging have primarily focused on individual domains, resulting in a lack of a comprehensive understanding of the multi-systemic dysregulation that occurs in aging. Methods: PhenoAge was evaluated based on a linear combination of chronological age (CA) and 9 clinical biomarkers in 952 multi-ethnic Asian women of reproductive age. Phenotypic age acceleration (PhenoAgeAccel), an aging biomarker, represents PhenoAge after adjusting for CA. This study conducts an in-depth association analysis of PhenoAgeAccel with clinical, nutritional, lipidomic, gut microbiome, and genetic factors. Results: Higher adiposity, glycaemia, plasma saturated fatty acids, kynurenine pathway metabolites, GlycA, riboflavin, nicotinamide, and insulin-like growth factor binding proteins were positively associated with PhenoAgeAccel. Conversely, a healthier diet and higher levels of pyridoxal phosphate, all-trans retinol, betaine, tryptophan, glutamine, histidine, apolipoprotein B, and insulin-like growth factors were inversely associated with PhenoAgeAccel. Lipidomic analysis found 132 lipid species linked to PhenoAgeAccel, with PC(O-36:0) showing the strongest positive association and CE(24:5) demonstrating the strongest inverse association. A genome-wide association study identified rs9864994 as the top genetic variant (P = 5.69E-07) from the ZDHHC19 gene. Gut microbiome analysis revealed that Erysipelotrichaceae UCG-003 and Bacteroides vulgatus were inversely associated with PhenoAgeAccel. Integrative network analysis of aging-related factors underscored the intricate links among clinical, nutritional and lipidomic variables, such as positive associations between kynurenine pathway metabolites, amino acids, adiposity, and insulin resistance. Furthermore, potential mediation effects of blood biomarkers related to inflammation, immune response, and nutritional and energy metabolism were observed in the associations of diet, adiposity, genetic variants, and gut microbial species with PhenoAgeAccel. Conclusions: Our findings provide a comprehensive analysis of aging-related factors across multiple platforms, delineating their complex interconnections. This study is the first to report novel signatures in lipidomics, gut microbiome and blood biomarkers specifically associated with PhenoAgeAccel. These insights are invaluable in understanding the molecular and metabolic mechanisms underlying biological aging and shed light on potential interventions to mitigate accelerated biological aging by targeting modifiable factors. [ABSTRACT FROM AUTHOR]

Background: Radiation enteritis (RE) is a common complication of radiotherapy for abdominal and pelvic tumors, adversely affecting treatment outcomes and patients' quality of life. Gut microbiome alterations may contribute to RE development, but the underlying pathogenic factors are not fully understood. This study aimed to characterize the intestinal microbial changes associated with RE and severe acute radiation enteritis (SARE) and to identify predictive biomarkers. Methods: We enrolled 50 cervical cancer patients undergoing radiotherapy and 15 healthy women (controls). Stool samples were collected at the baseline and during weeks 2, 4, and 6 of radiotherapy, and then analyzed using 16 S rDNA sequencing and bioinformatics. Results: Although the Bacteroidetes/Firmicutes (B/F) ratio was higher in patients with RE or SARE, it alone could not predict these conditions. Three enterotypes were identified based on dominant genera: Blautia (enterotype 1), Escherichia-Shigella (enterotype 2), and Faecalibacterium (enterotype 3). A decrease in Blautia and an increase in Escherichia-Shigella and Faecalibacterium were correlated with RE and SARE. Univariate logistic regression revealed that the Faecalibacterium enterotype at the baseline was associated with a 4.4-fold higher risk of developing SARE (odds ratio 5.400; P = 0.017). The Escherichia-Shigella enterotype was also linked to increased SARE incidence. Conclusion: These findings suggest that while single bacterial genera or the B/F ratio are insufficient predictors, enterotype classification may serve as a potential biomarker for predicting SARE in patients undergoing radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide, with obesity-induced lipid metabolism disorders playing a crucial role in its progression. A complex connection exists between gut microbiota and the development of intestinal tumors through the microbiota metabolite pathway. Metabolic disorders frequently alter the gut microbiome, impairing immune and cellular functions and hastening cancer progression. Methods: This study thoroughly examined the gut microbiota through 16S rRNA sequencing of fecal samples from 181 CRC patients, integrating preoperative Low-density lipoprotein cholesterol (LDL-C) levels and RNA sequencing data. The study includes a comparison of microbial diversity, differential microbiological analysis, exploration of the associations between microbiota, tumor microenvironment immune cells, and immune genes, enrichment analysis of potential biological functions of microbe-related host genes, and the prediction of LDL-C status through microorganisms. Results: The analysis revealed that differences in α and β diversity indices of intestinal microbiota in CRC patients were not statistically significant across different LDL-C metabolic states. Patients exhibited varying LDL-C metabolic conditions, leading to a bifurcation of their gut microbiota into two distinct clusters. Patients with LDL-C metabolic irregularities had higher concentrations of twelve gut microbiota, which were linked to various immune cells and immune-related genes, influencing tumor immunity. Under normal LDL-C metabolic conditions, the protective microorganism Anaerostipes_caccae was significantly negatively correlated with the GO Biological Process pathway involved in the negative regulation of the unfolded protein response in the endoplasmic reticulum. Both XGBoost and MLP models, developed using differential gut microbiota, could forecast LDL-C levels in CRC patients biologically. Conclusions: The intestinal microbiota in CRC patients influences the LDL-C metabolic status. With elevated LDL-C levels, gut microbiota can regulate the function of immune cells and gene expression within the tumor microenvironment, affecting cancer-related pathways and promoting CRC progression. LDL-C and its associated gut microbiota could provide non-invasive markers for clinical evaluation and treatment of CRC patients. [ABSTRACT FROM AUTHOR]

Previous studies have suggested a potential association between the gut microbiota and arthritis. However, the causal links between the gut microbiota and various types of arthritis, as well as the potential mediating role of inflammatory proteins, remain unclear. Mendelian randomization was used to explore the causal relationships between gut microbiota, inflammatory proteins, and various forms of arthritis (osteoarthritis, rheumatoid and psoriatic arthritis, and ankylosing spondylitis [AS]). The inverse variance-weighted method was the primary analytical approach used. Furthermore, we examined the mediating role of inflammatory proteins in the pathway linking the gut microbiota to arthritis. Sensitivity analyses were performed to verify the robustness of the findings, and enrichment analyses were conducted to investigate the biological functions and pathways involved. We identified 11 positive and 14 negative causal effects linking the genetic liability of the gut microbiota to arthritis. Similarly, 9 positive and 8 negative causal effects between inflammatory proteins and arthritis were identified. Notably, an increased abundance of the order Bacillales (odds ratio [OR] = 1.199, 95% confidence interval [CI] = 1.030–1.394, P = 0.019) and higher interleukin-7 levels (OR = 1.322, 95% CI = 1.004–1.741, P = 0.046) significantly elevated the risk of AS. Furthermore, interleukin-7 mediated 13.8% of the effect caused by the order Bacillales, with a mediation effect size of β = 0.025 (95% CI = 0.001–0.064). Sensitivity and supplementary analyses revealed no significant evidence of horizontal pleiotropy or heterogeneity. Overall, our findings demonstrate causal links between the gut microbiota, inflammatory proteins, and four arthritis types, highlighting the gut microbiota as a potential therapeutic target. Crucially, interleukin-7 not only strongly correlated with AS but also partially mediated the effect exerted by the gut microbiota on AS, suggesting that managing the gut microbiota to modulate inflammatory proteins could serve as an effective therapeutic strategy for arthritis. [ABSTRACT FROM AUTHOR]

Background: Weaning stress-induced diarrhea is widely recognized as being associated with gut microbiota dysbiosis. However, it has been challenging to clarify which specific intestinal microbiota and their metabolites play a crucial role in the antidiarrhea process of weaned piglets. Results: In this study, we first observed that piglets with diarrhea exhibited a lower average daily gain and higher diarrhea score, and elevated levels of lipopolysaccharide (LPS) and D-lactate (D-LA) compared to healthy piglets. Subsequently, we analyzed the differences in intestinal microbial composition and metabolite levels between healthy and diarrheal weaned piglets. Diarrheal piglets demonstrated intestinal microbiota dysbiosis, characterized primarily by a higher Firmicutes to Bacteroidota ratio, a deficiency of Lactobacillus amylovorus and Lactobacillus reuteri, and an increased abundance of Bacteroides sp.HF-5287 and Bacteroides thetaiotaomicron. Functional profiling of the gut microbiota based on Kyoto Encyclopedia of Genes and Genomes (KEGG) data was performed, and the results showed that tryptophan metabolism was the most significantly inhibited pathway in piglets with diarrhea. Most tryptophan metabolites were detected at lower concentrations in diarrheal piglets than in healthy piglets. Furthermore, we explored the effects of dietary indole-3-aldehyde (IAld), a key tryptophan metabolite, on intestinal development and gut barrier function in weaned piglets. Supplementation with 100 mg/kg IAld in the diet increased the small intestine index and improved intestinal barrier function by promoting intestinal stem cell (ISC) expansion in piglets. The promotion of ISC expansion by IAld was also confirmed in porcine intestinal organoids. Conclusions: These findings revealed that intestinal microbial tryptophan metabolite IAld alleviates impaired intestinal development by promoting ISC expansion in weaned piglets. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is a sexually transmitted virus, whose persistent infection is the main reason for invasive cervical cancer (ICC), which is the fourth most common type of cancer in women, with more than 500 000 new cases every year. After infection, various alterations occur in the host, facilitating the virus's evasion of immune system clearance and promoting its proliferation. Oral probiotic consumption can influence the whole body's immunity, inflammatory reflection, neural, endocrine humoral, metabolic pathways and other organs by adjusting the components of gut microbiota (GM). Some evidence shows there is a tight connection between GM and vaginal microbiota (VM), which is referred to as the gut‐vaginal axis. This review investigates the potential role of probiotics in clearing HPV via the gut‐vagina axis, emphasizing the effectiveness of Lactobacillus in preventing vaginal diseases and suggesting its potential for HPV clearance. Understanding the role of probiotics in the gut‐vagina axis could pave the way for new strategies to reduce and eliminate HPV and related diseases. [ABSTRACT FROM AUTHOR]

The rapid advancements in sequencing technologies and bioinformatics have enabled metagenomic research of complex microbial systems, but reliable results depend on consistent laboratory and bioinformatics approaches. Current efforts to identify best practices often focus on optimizing specific steps, making it challenging to understand the influence of each stage on microbial population analysis and compare data across studies. This study evaluated DNA extraction, library construction methodologies, sequencing platforms, and computational approaches using a dog stool sample, two synthetic microbial community mixtures, and various sequencing data sources. Our work, the most comprehensive evaluation of metagenomic methods to date. We developed a software tool, termed minitax, which provides consistent results across the range of platforms and methodologies. Our findings showed that the Zymo Research Quick-DNA HMW MagBead Kit, Illumina DNA Prep library preparation method, and the minitax bioinformatics tool were the most effective for high-quality microbial diversity analysis. However, the effectiveness of pipelines or method combinations is sample-specific, making it difficult to identify a universally optimal approach. Therefore, employing multiple approaches is crucial for obtaining reliable outcomes in microbial systems. Evaluation of metagenomic methods for gut microbiome profiling using dog stool and microbial standards, leading to the development of minitax tool. Optimal wetlab and analysis pipelines are recommended for reliable crossplatform microbiome studies. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) asscociated hepatocellular carcinoma (HCC) is becoming a growing concern in global healthcare. The early-life gut microbiota plays a crucial role in maintaining healthy. However, the impact of early-life gut microbiota dysbiosis on the advancement of MASLD-HCC remains inadequately understood. Methods: In the present study, we investigated the role of early-life gut microbiota in the development of MASLD-HCC in streptozotocin and high-fat diet (STZ-HFD) induced mouse model. We recorded the body weight and lifespan, and dynamically monitored the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (T-CHO) and blood glucose in the serum monthly. In addition, we examined various immune cells present in the liver, such as T cells, B cells, NK cells, NKT cells, αβT cells, γδT cells, macrophage and MDSC cells by flow cytometry and conducted liquid chromatography mass spectrometry (LC–MS) based analysis on liver tissue from control and early-life antibiotic exposure mice (early-Abx) MASLD-HCC mice. Results: We found that early-Abx mice suffered from more severe tumor burden and further confirmed that hepatocytes and immune cells were all disturbed. Importantly, early-life antibiotic exposure alters the liver metabolic profiling especially glycerophospholipids and lipid accumulation. Furthermore, mice exposed to antibiotics in early-life showed disturbances in glucose metabolism and developed insulin resistance. Conclusions: Collectively, our findings revealed that early-life antibiotic exposure accelerated the progression of MASLD-HCC by impairing the hepatocytes, immune homeostasis and metabolites persistently, highlighting the importance of the early-life microbiota in the development of MASLD-HCC. [ABSTRACT FROM AUTHOR]