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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.

Aims: Our study, employing a multi-omics approach, aimed to delineate the distinct gut microbiota and metabolic characteristics in individuals under 30 with unclassified diabetes, thus shedding light on the underlying pathophysiological mechanisms Methods: This age- and sex-matched case-control study involved 18 patients with unclassified diabetes, 18 patients with classic type 1 diabetes, 13 patients with type 2 diabetes, and 18 healthy individuals. Metagenomics facilitated the profiling of the gut microbiota, while untargeted liquid chromatography-mass spectrometry was used to quantify the serum lipids and metabolites. Results: Our findings revealed a unique gut microbiota composition in unclassified diabetes patients, marked by a depletion of Butyrivibrio proteoclasticus and Clostridium and an increase in Ruminococcus torques and Lachnospiraceae bacterium 8_1_57FAA. Comparative analysis identified the combined marker panel of five bacterial species, seven serum biomarkers, and three clinical parameters could differentiate patients with UDM from HCs with an AUC of 0.94 (95% CI 0.85–1). Notably, the gut microbiota structure of patients with unclassified diabetes resembled that of type 2 diabetes patients, especially regarding disrupted lipid and branched-chain amino acid metabolism. Conclusions: Despite sharing certain metabolic features with type 2 diabetes, unclassified diabetes presents unique features. The distinct microbiota and metabolites in unclassified diabetes patients suggest a significant role in modulating glucose, lipid, and amino acid metabolism, potentially influencing disease progression. Further longitudinal studies are essential to explore therapeutic strategies targeting the gut microbiota and metabolites to modify the disease trajectory. [ABSTRACT FROM AUTHOR]

Background: Constipation is a common symptom in maintenance hemodialysis patients and greatly affects the quality of survival of hemodialysis patients. Fecal microbiota transplantation and probiotics are feasible treatments for functional constipation, but there is still a gap in the research on the characteristics of gut flora in patients with maintenance hemodialysis combined with constipation. The aim of this study is to clarify the characteristics of the intestinal flora and its changes in maintenance hemodialysis patients with constipation. Methods: Fecal samples were collected from 45 participants, containing 15 in the maintenance hemodialysis constipation group,15 in the maintenance hemodialysis non-constipation group and 15 in the healthy control group. These samples were analyzed using 16S rRNA gene sequencing. The feature of the intestinal microbiome of maintenance hemodialysis constipation group and the microbiome differences among the three groups were elucidated by species annotation analysis, α-diversity analysis, β-diversity analysis, species difference analysis, and predictive functional analysis. Results: The alpha diversity analysis indicated that maintenance hemodialysis constipation group was less diverse and homogeneous than maintenance hemodialysis non-constipation group and healthy control group. At the genus level, the top ten dominant genera in maintenance hemodialysis constipation group patients were Enterococcus, Escherichia-Shigella, Bacteroides, Streptococcus, Bifidobacterium, Ruminococcus_gnavus_group, Lachnospiraceae_unclassified, Faecalibacterium, Akkermansia and UCG-002. Compared with non-constipation group, the Enterococcus, Rhizobiales_unclassified, Filomicrobium, Eggerthella, Allobaculum, Prevotella_7, Gordonibacter, Mitochondria_unclassified, Lachnoanaerobaculum were significantly higher in constipation group (p<0.05). Compared with non-constipation group, the Kineothrix, Rhodopirellula, Weissella were significantly lower in constipation group (p<0.05). The predictive functional analysis revealed that compared with non-constipation group, constipation group was significantly enriched in pathways associated with pyruate metabolism, flavonoid biosynthesis. Conclusions: This study describes for the first time the intestinal microbiome characteristics of maintenance hemodialysis patients with constipation. The results of this study suggest that there is a difference in the intestinal flora between maintenance hemodialysis patients with constipation and maintenance hemodialysis patients without constipation. [ABSTRACT FROM AUTHOR]

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]

Background: Disturbances in the gut microbiota may act as mechanisms influencing the interplay between dietary factors and metabolic disorders. Studies have demonstrated that these alterations are associated with the diagnosis of polycystic ovary syndrome (PCOS). Within this context, we aimed to investigate associations between gut microbiota, gut-derived metabolites (short-chain fatty acids [SCFAs] and indole-3-propionic acid [IPA]), and dietary intake in women with PCOS. Methods: We conducted a cross-sectional study of 24 women with PCOS, previously recruited for two studies at our research center, compared with 14 age-matched healthy controls. The mean (SD) age of all 38 participants was 33.3 (7.5) years, and the mean (SD) body mass index was 29.5 (4.8) kg/m2. Primary outcomes included gut microbiota analysis by sequencing the V4 region of the 16 S rRNA gene, serum IPA levels measured by liquid chromatography/triple-quadrupole mass spectrometry (LC-QqQ-MS), and fecal and plasma SCFA levels measured by LC-MS/MS. Results: Gut microbiota diversity, composition, and metabolic pathways differed between the PCOS and control groups. A higher abundance of two operational taxonomic units specializing in complex carbohydrate metabolism was observed in healthy control women. The PCOS group exhibited a less favorable dietary intake than the control group, and a significant correlation was observed between gut microbiota composition and dietary glycemic load in PCOS (r = 0.314, P = 0.03 in Mantel test). Multivariable-adjusted linear regression models indicated that lower levels of IPA and higher circulating levels of two SCFAs (acetic acid and propionic acid) were independently associated with the diagnosis of PCOS. Conclusions: Our data support the differentiation between women with PCOS and healthy controls based on gut microbiota analysis. Furthermore, changes in gut bacteria and their metabolites could be, at least in part, the biological mechanism by which a low glycemic load diet may potentially improve PCOS-related reproductive and cardiometabolic outcomes. [ABSTRACT FROM AUTHOR]

Changes in lung and gut microbial communities have been associated with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate correlations between microbial changes in the lung and gut and host physiological indices in an IPF model, exploring potential mechanisms of the lung-gut axis in IPF pathogenesis. IPF model rats were established via trans-tracheal injection of bleomycin, with assessments of hematological indices, serum cytokines, lung histopathology, and microbiome alterations. Significant differences in microbial structure and composition were observed in the IPF model compared to controls, with 14 lung and 7 gut microbial genera showing significant abundance changes. Further analysis revealed 20 significant correlations between pulmonary and gut genera. Notably, 11 pairs of correlated genera were linked to the same IPF-related physiological indices, such as hydroxyproline, mean corpuscular volume (MCV), and red cell distribution width-standard deviation (RDW-SD). We identified 24 instances where a lung and a gut genus were each associated with the same physiological index, forming "lung genus—index—gut genus" relationships. Mediation analysis showed that indices like hydroxyproline, MCV, and RDW-SD mediated correlations between 10 lung genera (e.g., Cetobacterium, Clostridium XVIII) and the gut genus Allobaculum. This study first describes gut-lung microbial interactions in pulmonary fibrosis. Mediation analysis suggests pathways underlying "lung genus—host index—gut genus" and "gut genus—host index—lung genus" correlations, thus providing clues to further elucidate the mechanisms of the "gut-lung axis" in IPF pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Research has demonstrated that obesity may be associated with rheumatoid arthritis (RA). In addition, Dysbiosis of intestinal microbiota and their metabolites has been linked to the occurrence and development of RA and obesity. However, the mechanism by which obesity affects RA remains unclear.In this study, we explored the impact of high fat diet(HFD) on collagen-induced arthritis (CIA) rats and revealed its mechanisms based on gut microbiota and metabolomics. Methods: Based on diet and modeling, rats were divided into normal group (Con), CIA model group, HFD group (HFD), and HFD + CIA group (HCIA). The effect of HFD on arthritis in CIA rats were investigated based on the arthritis index (AI), weight, blood lipid levels, and inflammatory cytokines. Moreover, HE staining and micro-CT were performed to evaluated the effect of HFD on the pathology of joints and synovial tissues in CIA rats.16S rRNA amplicon sequencing and liquid chromatography-mass spectrometry (LC–MS) were employed to explore changes in gut microbiota and short-chain fatty acids (SCFAs). Results: The AI scores, inflammatory cytokines and bone destruction parameters in the HCIA group were significantly higher than those in the other three groups. The results of 16S rRNA amplicon sequencing and metabolomics showed that compared with the other three groups, the expression of g_Muribaculaceae and butyric acid were reduced in the HCIA group. Spearman and linear correlation analyses revealed a positive correlation between g_Muribaculaceae abundance and butyric acid levels. Conclusions: HFD stimulated butyric acid metabolism dysbiosis, altered microbiota, and aggravated inflammatory response in CIA rats. [ABSTRACT FROM AUTHOR]

Background: Hashimoto's thyroiditis (HT) is an autoimmune disorder with unclear molecular mechanisms. While current diagnosis is well-established, understanding of the gut-thyroid axis in HT remains limited. This study aimed to uncover novel molecular signatures in HT by integrating gut metagenome and host transcriptome data (miRNA/mRNA), potentially elucidating disease pathogenesis and identifying new therapeutic targets. Methods: We recruited 31 early HT patients and 30 healthy controls in a two-stage study (discovery and validation). Blood and fecal samples underwent RNA and metagenomic sequencing, respectively. Integrative analysis included differential expression, weighted correlation network, correlation and random forest analyses. Regression models and ROC curve analysis were used to evaluate the significance of identified molecular signatures in HT. Results: Integrative analysis revealed subtle changes in gut microbiota diversity and composition in early HT, increased abundance of Bacillota_A and Spirochaetota at the phylum level, and significant differences in 24 genera and 67 species. Ecological network analysis indicated an imbalance in the gut microbiota with reduced inhibitory interactions against pathogenic genera in HT. Functional analysis showed changes in infection- and immune-related pathways. Three characteristic species (Salaquimonas_sp002400845, Clostridium_AI_sp002297865, and Enterocloster_citroniae) were identified as most relevant to HT. Analysis of miRNA and mRNA expression profiles uncovered pathways related to immune response, inflammation, infection, metabolism, proliferation, and thyroid cancer in HT. Based on correlations with HT and interactions between them, six characteristic RNAs (hsa-miR-548aq-3p, hsa-miR-374a-5p, GADD45A, IRS2, SMAD6, WWTR1) were identified. Furthermore, our study uncovered significant gut microbiota-host transcriptome interactions in HT, revealing enrichment in metabolic, immune, and cancer-related pathways, particularly with strong associations among those 9 key molecular signatures. The validation stage confirmed improved HT classification accuracy by combining these signatures (AUC = 0.95, ACC = 0.85), suggesting their potential significance in understanding HT pathogenesis. Conclusion: Our study reveals novel molecular signatures linking gut microbiome and host transcriptome in HT, providing new insights into the disease pathogenesis. These findings not only enhance our understanding of the gut-thyroid axis but also suggest potential new directions for therapeutic interventions in HT. [ABSTRACT FROM AUTHOR]

Background: Advanced-stage non-small cell lung cancer (NSCLC) poses treatment challenges, with immune checkpoint inhibitors (ICIs) as the main therapy. Emerging evidence suggests the gut microbiome significantly influences ICI efficacy. This study explores the link between the gut microbiome and ICI outcomes in NSCLC patients, using metatranscriptomic (MTR) signatures. Methods: We utilized a de novo assembly-based MTR analysis on fecal samples from 29 NSCLC patients undergoing ICI therapy, segmented according to progression-free survival (PFS) into long (> 6 months) and short (≤ 6 months) PFS groups. Through RNA sequencing, we employed the Trinity pipeline for assembly, MMSeqs2 for taxonomic classification, DESeq2 for differential expression (DE) analysis. We constructed Random Forest (RF), Support Vector Machine (SVM), and Extreme Gradient Boosting (XGBoost) machine learning (ML) algorithms and comprehensive microbial profiles. Results: We detected no significant differences concerning alpha-diversity, but we revealed a biologically relevant separation between the two patient groups in beta-diversity. Actinomycetota was significantly overrepresented in patients with short PFS (vs long PFS, 36.7% vs. 5.4%, p < 0.001), as was Euryarchaeota (1.3% vs. 0.002%, p = 0.009), while Bacillota showed higher prevalence in the long PFS group (66.2% vs. 42.3%, p = 0.007), when comparing the abundance of corresponding RNA reads. Among the 120 significant DEGs identified, cluster analysis clearly separated a large set of genes more active in patients with short PFS and a smaller set of genes more active in long PFS patients. Protein Domain Families (PFAMs) were analyzed to identify pathways enriched in patient groups. Pathways related to DNA synthesis and Translesion were more enriched in short PFS patients, while metabolism-related pathways were more enriched in long PFS patients. E. coli-derived PFAMs dominated in patients with long PFS. RF, SVM and XGBoost ML models all confirmed the predictive power of our selected RNA-based microbial signature, with ROC AUCs all greater than 0.84. Multivariate Cox regression tested with clinical confounders PD-L1 expression and chemotherapy history underscored the influence of n = 6 key RNA biomarkers on PFS. Conclusion: According to ML models specific gut microbiome MTR signatures' associate with ICI treated NSCLC outcomes. Specific gene clusters and taxa MTR gene expression might differentiate long vs short PFS. [ABSTRACT FROM AUTHOR]

Background: Premature infants are more prone to brain injuries owing to incomplete nervous system development and poor adaptation outside the mother's body. Without timely intervention, premature infants with brain injuries often develop intellectual disabilities, causing significant burdens on families and the society. Multiple studies have shown that gut dysbiosis can affect the nervous system, and vice versa. This study aimed to explore the changes in gut microbiota of typical premature infants and those with brain injuries on the third and seventh days after birth using 16 S rRNA technology. Methods: Fecal samples from typical premature infants (non-brain injury group, n = 17) and those with brain injuries (brain injury group, n = 21) were collected on days 1, 3, and 7 after birth for 16 S rRNA sequencing. Alpha diversity analysis was used to evaluate the diversity of gut microbiome. LEfSe and DESeq2 were used to analyze of the microorganisms' characteristics and differentiate the microorganisms between the two groups. Results: At the phylum level, Firmicutes, Proteobacteria, and Actinobacteria were the dominant flora in both groups. At the genus level, the proportion of Enterococcus in fecal samples of the brain injury group was higher than that of the non-brain injury group on day three after birth; however, the opposite was observed on day seven. Rothia and Lactobacillales were characteristic bacteria of the non-brain injury group on days three and seven after birth, whereas Enterococcus and Bifidobacteria were characteristic bacteria of the brain injury group on days three and seven after birth, respectively. Three days after birth, the Shannon and Simpson indices of the non-brain injury group were significantly higher than those of the brain injury group. Conclusion: Premature infants with brain injuries have a unique gut microbiota that is different from that of typical premature infants, indicating correlation between brain injuries and gut microbiota. [ABSTRACT FROM AUTHOR]

Sea urchins, ecologically important marine species, host a complex gut microbiota that plays a significant role in their digestion, nutrient acquisition, and overall health. The gut microbes, along with endogenous enzymes, facilitate the breakdown of macroalgae and other food sources. Environmental factors, including temperature, salinity, and habitat type, can greatly influence the microbial communities within sea urchins. Dietary variations can also lead to shifts in the abundance and composition of intestinal bacteria, highlighting the strong connection between diet and gut microbiota. The sea urchin's unique anatomy and digestive system adaptations contribute to their ability to process and absorb nutrients efficiently, supporting their varied diets. Gut microbes not only participate in the decomposition of complex carbohydrates, but also in detoxifying compounds and mitigating the impacts of inhospitable environments. Further research is needed to fully understand the intricate relationships between sea urchin species, their habitats, diets, and gut microbiota composition. A deeper understanding of these interactions may inform sustainable management and aquaculture strategies, ensure the long‐term viability of economically valuable sea urchin species, and provide insights into their ecological roles and adaptability to changing environments. [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]

To explore the effects of hydroxyl‐α‐sanshool (HAS) administration on the intestinal health of high‐fat diet‐fed mice, mice were separated into a control (CN) group, a model (MC) group, a HAS (8 mg/kg bw) (HD) group, and a HAS (8 mg/kg bw) + Compound C (10 mg/kg·4 d) (HA) group. After 4 weeks of treatment, the mice were fasted for 12 h prior to sacrifice, and autopsy samples were taken for analysis. HAS improved inflammatory and metabolic imbalances by activating AMPK, as shown by biochemical, microbiota composition, and metabolomics analyses. These findings suggest that HAS can maintain intestinal health through AMPK‐mediated amino acid metabolism. [ABSTRACT FROM AUTHOR]

The composition of the gut microbiota is a known factor in various diseases and has proven to be a strong basis for automatic classification of disease state. A need for a better understanding of microbiota data on the functional scale has since been voiced, as it would enhance these approaches' biological interpretability. In this paper, we have developed a computational pipeline for integrating the functional annotation of the gut microbiota into an automatic classification process and facilitating downstream interpretation of its results. The process takes as input taxonomic composition data, which can be built from 16S or whole genome sequencing, and links each component to its functional annotations through interrogation of the UniProt database. A functional profile of the gut microbiota is built from this basis. Both profiles, microbial and functional, are used to train Random Forest classifiers to discern unhealthy from control samples. SPARTA ensures full reproducibility and exploration of inherent variability by extending state-of-the-art methods in three dimensions: increased number of trained random forests, selection of important variables with an iterative process, repetition of full selection process from different seeds. This process shows that the translation of the microbiota into functional profiles gives non-significantly different performances when compared to microbial profiles on 5 of 6 datasets. This approach's main contribution however stems from its interpretability rather than its performance: through repetition, it also outputs a robust subset of discriminant variables. These selections were shown to be more consistent than those obtained by a state-of-the-art method, and their contents were validated through a manual bibliographic research. The interconnections between selected taxa and functional annotations were also analyzed and revealed that important annotations emerge from the cumulated influence of non-selected taxa. Author summary: The field of personalized medicine has major stakes in using an individual's microbiota as a descriptor of health. This raises the question of the interpretability of microbiotal signatures found for various diseases. To gain insight into this matter, we developed the SPARTA (Shifting Paradigms to Annotation Representation from Taxonomy to identify Archetypes) pipeline to highlight and interlink significantly discriminating taxa and metabolic functions. SPARTA relies on the integration of the information from the UniProt database concerning the gut microbiota's functional annotation to microbial abundance data, and Machine Learning classification, with the novel preconception of keeping explicit and thorough information on the connections between taxa and annotations. Through iteration, this method can output a reduced list of the microbiotas' descriptors, both in terms of microbial taxa and functions, with insight into their robustness, for better ease of downstream interpretation. The selection was compared to state-of-the-art approaches, and its contents were validated through a manual bibliographic check of its outputs. Finally, we highlight how discriminant metabolic functions may arise from the aggregation of several low-abundance taxa, giving visibility to these functions which are therefore not easily derivable from approaches based on microbial composition, marking them as potentially novel leads. [ABSTRACT FROM AUTHOR]

Primary biliary cholangitis (PBC) and gut microbiota (GM) are epidemiologically correlated but the causal inter-relationships remain poorly understood. We aim to explore the causal relationships between GM and PBC. Using the MiBioGen consortium, GWAS data for GM at the species level and the largest publicly available PBC GWAS data to date, we performed a bidirectional two-sample Mendelian randomization by the inverse variance weighted, MR-Egger, weighted median, weighted model and MR-PRESSO to elucidate the potential causal role of GM in PBC. To measure the heterogeneity of instrumental variables (IV), Cochran's Q statistic and MR-Egger intercept test were used. Genetically instrumented order Coriobacteriales (odds ratio [OR] = 2.18, 95% confidence interval [CI] 1.30–3.66, P = 0.004) significantly increased the risk for PBC, while genetically driven class Deltaproteobacteria (OR = 0.52, 95% CI 0.36–0.74, P = 0.002) causally decrease the NAFLD risk. Reverse MR analysis showed no significant association between PBC and the two specific GM. However, it indicated that PBC progression significantly increases the abundance of the class Bacteroidia, order Bacteroidales, and phylum Bacteroidetes (OR = 1.02, 95% CI 1.002–1.03, P = 0.026), while decreasing the abundance of the genus Lachnospiraceae UCG010 (OR = 0.98, 95% CI 0.96–0.995, P = 0.026). Our study demonstrated that genetically driven order Coriobacteriales and class Deltaproteobacteria were causally related to PBC risk. This causality provided a new perspective on ameliorating PBC by modulating GM. Our study demonstrated that genetically driven order Coriobacteriales and class Deltaproteobacteria were causally related to PBC risk. PBC was causally related to the abundance of four GM taxa(class Bacteroidia, order Bacteroidales, phylum Bacteroidetes and genus Lachnospiraceae UCG010). This causality provided a new perspective on ameliorating PBC by modulating GM. [ABSTRACT FROM AUTHOR]

Background: Gut microbiome plays a significant role in longevity, and dysbiosis is indeed one of the hallmarks of aging. However, the causal relationship between gut microbiota and human longevity or aging remains elusive. Methods: Our study assessed the causal relationships between gut microbiome and longevity using Mendelian Randomization (MR). Summary statistics for the gut microbiome were obtained from four genome-wide association study (GWAS) meta-analysis of the MiBioGen consortium (N = 18,340), Dutch Microbiome Project (N = 7738), German individuals (N = 8956), and Finland individuals (N = 5959). Summary statistics for Longevity were obtained from Five GWAS meta-analysis, including Human healthspan (N = 300,447), Longevity (N = 36,745), Lifespans (N = 1,012,240), Parental longevity (N = 389,166), and Frailty (one of the primary aging-linked physiological hallmarks, N = 175,226). Results: Our findings reveal several noteworthy associations, including a negative correlation between Bacteroides massiliensis and longevity, whereas the genus Subdoligranulum and Alistipes, as well as species Alistipes senegalensis and Alistipes shahii, exhibited positive associations with specific longevity traits. Moreover, the microbial pathway of coenzyme A biosynthesis I, pyruvate fermentation to acetate and lactate II, and pentose phosphate pathway exhibited positive associations with two or more traits linked to longevity. Conversely, the TCA cycle VIII (helicobacter) pathway consistently demonstrated a negative correlation with lifespan and parental longevity. Conclusions: Our findings of this MR study indicated many significant associations between gut microbiome and longevity. These microbial taxa and pathways may potentially play a protective role in promoting longevity or have a suppressive effect on lifespan. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is a highly prevalent pathogen in human gastric mucosa epithelial cells with strong colonization ability. Weizmannia coagulans is a kind of active microorganism that is beneficial to the improvement of host gut microbiota balance and can prevent and treat intestinal diseases. We investigated the beneficial effects of W. coagulans BC99 in H. pylori infected mice and measured inflammation response, oxidative stress, and gut microbiota. Results showed that BC99 could alleviate the gastric inflammation, inhibit the increasing of inflammation parameters endotoxin, interleukin‐10, transforming growth factor‐β, and interferon‐γ and oxidative stress myeloperoxidase and malondialdehyde, promote the levels of superoxide dismutase and catalase. Furthermore, 16S rRNA gene sequencing analysis revealed that BC99 reversed the change of gut microbiota by reducing the abundance of Olsenella, Candidatus_Saccharimonas, Monoglobus, and increasing the abundance of Tyzzerella. Meanwhile, BC99 caused elevated levels of Ligilactobacillus and Lactobacillus. In view of the beneficial effect of BC99 on the content of short‐chain fatty acid, valeric acid with sodium valerate interfered with H. pylori infection in mice found that valeric acid had a good restorative effect of H. pylori infection relating inflammation and oxidative stress responses. These results suggest that W. coagulans BC99 can be used as a potential probiotic to prevent and treat H. pylori infection by regulating the inflammation, oxidative stress, and gut microbiota. [ABSTRACT FROM AUTHOR]

Background Material and methods Results Conclusion The objective of the current study was to investigate the potential effects of syringin against dextran sulphate colitis (DSS)‐induced ulcerative colitis (UC) in mice.In vitro study was performed on the RAW 264.7 cells and cytokines and inflammatory level were estimated. The oxidative stress, inflammatory cytokines, apoptosis and inflammatory parameters were estimated. The mRNA expression and faecal samples were estimated in the colon tissue.Syringin treatment enhanced the body weight, colon length and reduced the disease activity index (DAI), spleen index. Syringin treatment remarkably suppressed the level of nitric oxide (NO), myeloperoxidase (MPO), intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule 1 (VCAM‐1) along with alteration of antioxidant parameters. Syringin treatment also altered level of cytokines in the serum and colon tissue; inflammatory parameters viz., platelet‐activating factor (PAF), cyclooxygenase‐2 (COX‐2), prostaglandin (PGE2), inducible nitric oxide synthetase (iNOS), nuclear factor κ‐B (NF‐κB); matrix metalloproteinases (MMP) level. Syringin significantly (p < 0.001) enhanced the level of nuclear factor erythroid 2‐related factor (Nrf2) and heme oxygenase‐1 (HO‐1). Syringin remarkably altered the relative abundance of gut microbiota like Firmicutes, Bacteroidetes, F/B ratio, Verrucomicrobia and Actinobacteria.Syringin exhibited the protective effect against DSS‐induced UC in mice via alteration of NF‐κB signalling pathway. [ABSTRACT FROM AUTHOR]

Diversity and heterogeneity often are conflated but are fundamentally different. An aphorism proposed by Shavit and Ellison (2021; J. Phil. 118: 525–548) for distinguishing them is that ‘a zoo is diverse whereas an ecosystem is heterogeneous.' That is, a zookeeper measuring diversity simply enumerates the different types of animals; interactions are not expected to occur between animals separated by fences or other barriers. In contrast, measures of heterogeneity ought to include both interspecific interactions and relationships between species and their heterogeneous habitats. Here, we use cross‐scale, dual scaling‐law analyses of heterogeneity and diversity of animal gut microbiomes (AGMs) to address three objectives: 1) estimate the spatial heterogeneity and diversity of animal‐gut microbiomes; 2) analyze influences of phylogeny and diets on scaling of diversity and heterogeneity; 3) explore mechanistic differences between diversity and heterogeneity in AGMs. From 4903 AGM samples collected from 318 animal species covering all six classes of vertebrates and four major classes of invertebrates, we estimated that ≈640 000 operational taxonomic units (OTUs or ‘species') make up the pool of microbial species that could inhabit animal guts, among which ≈8000 are relatively common and ≈800 are dominant. The gut of any single animal, however, includes only 0.01–0.5% of the total species pool. We applied Ma's diversity‐area relationship for scaling diversity, and extend Taylor's power law and Luna et al.'s (2020; Diversity 12: 86) interaction diversity for scaling heterogeneity. At the community scale, phylogeny significantly influenced heterogeneity, but diets did not. Phylogeny and diets had limited influence on diversity at both community and landscape scales. We demonstrated that diversity and heterogeneity measure two different properties. Further, differences in scaling of diversity and heterogeneity are a result of heterogeneity being primarily the result of evolved dispersal behavior and interspecific interactions, whereas diversity results from abundances controlled on ecological time scales. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions This study aimed to evaluate the impact of antibiotic exposure on efficacy and adverse reactions in non‐small cell lung cancer (NSCLC) patients receiving chemoimmunotherapy, and to explore any specific associations on the basis of antibiotic class.A retrospective study was conducted on NSCLC patients who received chemoimmunotherapy in two Shandong hospitals between January 2018 and October 2023. The association between antibiotic exposure and progression‐free survival (PFS), overall survival (OS), objective response rate (ORR) and incidence of immune related adverse reactions (irAE) of patients were evaluated.Of the 316 patients, 134 (42.41%) received antibiotics (ATB group), and 182 (57.59%) did not (N‐ATB group). There was no significant difference in PFS (aHR = 1.009, 95% CI: 0.770–1.323; p = 0.946) or OS (aHR = 1.420, 95% CI: 0.986–2.047; p = 0.060) between ATB and N‐ATB groups. The impact on efficacy was related to the type of antibiotic. β‐Lactams (aHR = 1.737, 95% CI: 1.148–2.629; p = 0.009), in particular β‐lactam/β‐lactamase inhibitor combinations (BLBLIs) (aHR = 1.885, 95% CI: 1.207–2.944, p = 0.005) were associated with poorer OS. However, quinolones (aHR = 1.192, 95% CI: 0.861–1.650; p = 0.291) were not associated with OS. The incidence of irAEs was not significantly different between ATB and N‐ATB groups (p = 0.073), but was higher with BLBLIs (p = 0.013).In NSCLC patients receiving chemoimmunotherapy, no significant difference was observed in efficacy and incidence of irAEs between the ATB and the n‐ATB groups. In antibiotic class analysis, β‐lactams and specifically BLBLIs were observed to be associated with worse OS. [ABSTRACT FROM AUTHOR]

Lomatogonium rotatum (LR) is a folk medicinal herb traditionally used as a lipid-lowering and anti-obesity agent; but its pharmacological mechanism is unclear. In this study, we assessed the alterations of LR on gut microbes and serum metabolites in obese mice and their associated mechanisms of modulation on visceral fat and serum lipid by integrating gut microbiota and metabolomics analyses. Mice were fed a high-fat diet (HFD) to generate obesity and were then given LR and Orlistat orally at different doses (0.18, 0.9, 1.8 g/kg for LR and 0.048 g/kg for Orlistat) for a duration of 9 weeks. The impact of LR on weight loss was assessed through the examination of fat deposition, serum lipid indices, liver indices, and HE pathohistology. The effects of LR on gut microbiota and serum metabolites in obese mice were then investigated by 16S rRNA sequencing technology and untargeted metabolomics, and correlation analysis was performed. LR significantly reduced body weight, feed intake, Lee's index, visceral fat accumulation, serum TG, TC, AST and ALT, and elevated serum HDL levels in obese mice. In addition, 16S rRNA sequencing results indicated that the LR intervention remodeled microbial diversity and composition, increased the relative abundance of gut microbes Bacteroidetes and Porphyromonadaceae in HFD-induced obese mice, and decreased the Deferribacteres , Firmicutes and the Firmicutes/Bacteroidetes ratio. Correlation analyses showed that LR regulation of L-tyrosine and hesperetin metabolism, as well as alterations in the metabolic pathways of Phenylalanine, tyrosine and tryptophan biosynthesis, were associated with the changes in abundance of Bacteroidetes , Firmicutes, Porphyromonadaceae and Deferribacteres. Our study demonstrated that LR has lipid lowering and visceral fat reduction effects and its function may be closely related to the improvement of the gut microbiota and its associated metabolites. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a rare and highly heterogeneous chronic autoimmune disease characterized by multi-organ and tissue fibrosis, often accompanied by a poor prognosis and high mortality rates. The primary pathogenic mechanisms of SSc are considered to involve tissue fibrosis, autoimmune dysfunction, and microvascular abnormalities. Recent studies have shed light on the gut microbiota (GM) and metabolites in SSc patients, revealing their association with gastrointestinal symptoms and disease phenotypes. However, further elucidation is needed on the specific mechanisms underlying the interactions between GM, metabolites, and the immune system and their roles in the pathogenesis of SSc. This review outlines the characteristics of GM and metabolites in SSc patients, exploring their interrelationships and analyzing their correlations with the clinical phenotypes of SSc. The findings indicate that while the α-diversity of GM in SSc patients resembles that of healthy individuals, notable differences exist in the β-diversity and the abundance of specific bacterial genera, which are closely linked to gastrointestinal symptoms. Moreover, alterations in the levels of amino acids and lipid metabolites in SSc patients are prominently observed and significantly associated with clinical phenotypes. Furthermore, this review delves into the potential immunopathological mechanisms of GM and metabolites in SSc, emphasizing the critical role of interactions between GM, metabolites, and the immune system in comprehending the immunopathological processes of SSc. These insights may offer new scientific evidence for the development of future treatment strategies. [ABSTRACT FROM AUTHOR]

Various problems and obstacles are encountered during pig farming, especially the weaning phase when switching from liquid to solid feed. Infection by pathogenic bacteria causes damage to the intestinal barrier function of piglets, disrupts the balance of the intestinal microbiota, and destroys the chemical, mechanical, and immune barriers of the intestinal tract, which is one of the main causes of gut inflammation or gut diseases in piglets. The traditional method is to add antibiotics to piglet diets to prevent bacterial infections. However, long-term overuse of antibiotics leads to bacterial resistance and residues in animal products, threatening human health and causing gut microbiota dysbiosis. In this context, finding alternatives to antibiotics to maintain pre- and post-weaning gut health in piglets and prevent pathogenic bacterial infections becomes a real emergency. The utilization of probiotics in piglet nutrition has emerged as a pivotal strategy to promote gut health and defend against pathogenic infections, offering a sustainable alternative to traditional antibiotic usage. This review introduces recent findings that underscore the multifaceted roles of probiotics in enhancing piglet welfare, from fortifying the gut barrier to mitigating the impacts of common bacterial pathogens. Meanwhile, this study introduces the functions of probiotics from different perspectives: positive effects of probiotics on piglet gut health, protecting piglets against pathogen infection, and the mechanisms of probiotics in preventing pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to investigate effect of energy levels on liver oxidative state and gut microbiota of laying hens fed a low-protein diet. Methods: A total of 216 laying hens (57-week-old with similar body weight) were randomly divided into 3 groups: low-energy and low-protein diet (LL: 10.73 MJ/kg), middle-energy and low-protein diet (ML: 11.15 MJ/kg), and high-energy and low-protein diet (HL: 11.57 MJ/kg) groups. The experiment lasted for 10 weeks. Results: Results showed that the liver MDA level was higher, while the liver T-AOC level was lower in the HL group compared with LL and ML groups. The dominant phyla in LL group, ML group, and HL group were Bacteroidetes (38.08%, 39.69%, and 40.93%) and Firmicutes (16.78%, 18.37%, and 17.44%). At the genus level, Alistipes (9.45%) was abundant in the LL group. Bacteroides (14.46%), Phocaeicola (4.48%) and Precotella (2.95%) were highest in the ML group. Parabacteroides (1.78%) and Desulfovibrio (1.02%) were highest in the HL group. At the species level, Bacteroides fragilis (0.42%) is lowest in LL group, Desulfovibrio piger increased with the increase of energy. MDA was significantly and positively correlated with Methanobrevibacter woesei between ML group and HL groups (p < 0.05). T-AOC was highly significantly and positively correlated with Phocaeicola sp. Sa1YUN3 (p < 0.01). Discussion: This study found that high-energy and low-protein diets might cause liver oxidative stress by gut microbes in the laying hens. [ABSTRACT FROM AUTHOR]

The gut microbiota of vertebrates is malleable and may be shaped by both intrinsic and extrinsic factors. Here, the effect that geography has on the cloacal microbiota of two species of Australian freshwater chelonians, eastern longneck turtle (Chelodina longicollis) and Macquarie River turtle (Emydura macquarii), captured from waterbodies with different levels of anthropogenic pressure was investigated. We analysed the microbiota composition, structure and diversity through 16S rRNA gene amplicon sequencing. It was hypothesised that animals from less disturbed environments would harbour a more diverse cloacal microbial population. The cloacal microbiotas from 93 turtles (C. longicollis n = 78; E. macquarii n = 15), from five locations, were analysed. For both species, the most predominant phylum was Proteobacteria. Cloacal microbiota alpha diversity varied significantly between the C. longicollis from all locations, but no differences were found for E. macquarii. In C. longicollis, turtles from wetlands within the centre of Melbourne had the lowest alpha diversity metrics, while the highest alpha diversity values were seen in turtles captured from an undisturbed rural waterbody. Beta diversity, obtained by weighted UniFrac distance, showed significant differences between locations of capture for both species of turtles in this investigation. For C. longicollis, 87 biomarkers were identified responsible for explaining differences between locations, and in E. macquarii, 42 biomarkers were found. This is the first study to explore the cloacal microbiota composition of the eastern longneck turtle and gives greater insight into microbial community structures in Macquarie River turtles. Our study demonstrated that cloacal microbiota composition of freshwater turtles was significantly influenced by locality and that disrupted environments may reduce microbial diversity in C. longicollis. Interestingly, we discovered that the effects of location contrasted significantly between species for alpha diversity with differences discovered for C. longicollis but not E. macquarii. However, for both species, beta diversity was notably influenced by habitat type. These results highlight the need to interpret chelonian microbiota data in the context of geography and human disturbance of the environment. [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]

Background: Gut microbiome dysbiosis and related immune dysfunction have been associated with the pathogenesis of Human Cytomegalovirus (HCMV) infection in infants with neonatal cholestasis (NC) as previously reported by us. However, the interaction of a perturbed microbiome, HCMV infection, and dysregulated immunity leading to exacerbation of disease severity has not been investigated so far. In this study, we examined the association of gut microbiome, host inflammatory and homeostatic markers that are likely to govern increased pathogenesis of NC in HCMV infected IgM positive infants (N = 15) compared to IgM negative (N = 15) individuals. Stool samples of HCMV infected infants and age-matched healthy controls (N = 10) were assessed for gut bacteria-derived metabolites like short-chain fatty acids (SCFAs), Lipopolysaccharide (LPS), cytokines and markers of gut barrier integrity. Data were correlated with previously determined gut microbiome composition and frequency of immune cell subsets. Finally, validation of clinical potential was undertaken by principal component analysis (PCA) of integrated data to delineate the spectrum of clinical pathology. Results: Significantly lower levels of SCFAs and elevated fecal levels of soluble inflammatory mediators were observed in IgM positive HCMV infected infants. Further, increased plasma LPS levels and markers of gut permeability, suggestive of microbial translocation due to a 'leaky gut' were observed in HCMV infected IgM positive group. PCA of integrated data revealed clearly disparate profiles representative of IgM positive, IgM negative, and uninfected healthy states. Conclusion: Our results suggest the utility of an integrated approach involving dysregulated microbiome-immune axis for gaining a better understanding of pathogenesis associated with HCMV infection in NC. [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]

Menopausal syndrome, occurring during the menopausal stage in women, manifests as symptoms stemming from decreased estrogen levels, such as hot flashes, insomnia, mental disorders (anxiety, depression), and osteoporosis. The bulk of studies have indicated alterations in the gut microbiota of those experiencing menopause syndrome compared to healthy women. However, This article focuses on the alterations in gut microbiota in perimenopausal women. Our study utilized 16 s rRNA sequencing to determine the differences in the gut microbiota and metabolites among 44 menopausal syndrome women. The distribution of gut microbiota in postmenopausal women varies based on the level of follicle stimulating hormone, with changes in gut microbiota abundance taking precedence over symptom onset. Fecal metabolites reveal changes in several metabolites, including Amino acid metabolism (Tyrosine, Tryptophan), Lipid metabolism (Alpha linolenic acid metabolism), and other metabolites. Disturbances in lipid metabolism, triggered by hormonal level fluctuations, can contribute to the development of osteoporosis. [ABSTRACT FROM AUTHOR]

This study is to investigate the relationship between the intestinal microbiota and urine levels of the ellagic acid-derived polyphenols, the urolithins, in a cohort of subjects following a three-week walnut dietary intervention. We longitudinally collected fecal and urine samples from 39 subjects before and after walnut consumption (2 oz per day for 21 days). 16S RNA gene sequencing was performed on fecal DNA to study the association between microbiota composition and the levels of nine urolithin metabolites, which were measured using UHPLC/Q-TOF–MS/MS. Fecal microbial composition was found to be significantly different between pre- and post-walnut intervention (beta diversity, FDR-p = 0.018; alpha diversity, p = 0.018). Roseburia, Rothia, Parasutterella, Lachnospiraceae UCG-004, Butyricicoccus, Bilophila, Eubacterium eligens, Lachnospiraceae UCG-001, Gordonibacter, Paraprevotella, Lachnospira, Ruminococcus torques, and Sutterella were identified as the 13 most significantly enriched genera after daily intake of walnuts. We observed 26 genera that were significantly associated with 7 urolithin metabolites, with 22 genera positively correlating after walnut supplementation (FDR-p ≤ 0.05). PICRUSt analysis showed that several inferred KEGG orthologs were associated with 4 urolithin metabolites after walnut intake. In this study, we found that walnut supplementation altered urolithin metabolites, which associates with specific changes in bacterial taxa and inferred functional contents. [ABSTRACT FROM AUTHOR]

Osteopontin (Opn) depletion can improve septic outcomes, but the underlying mechanism remains unknown. In this study, we demonstrated that nonhematopoietic but not hematopoietic Opn depletion improved septic outcomes. When compared with wild type mice, cohoused Opn −/− mice displayed enhanced production of antibacterial peptides (AMPs), decreased bacterial loads, and a distinct bacterial composition of gut microbiota. Fecal microbiota transplantation and OPN neutralization assay showed that Opn depletion could reduce bacterial loads and improve septic inflammation. By employing an intestinal organoid culture system, we proved that OPN neutralization in wild type organoids could inactivate AKT and decrease FOXO3a phosphorylation, resulting in enhanced AMP production, whereas OPN treatment in OPN-deficient organoids could activate AKT and increase FOXO3a phosphorylation, leading to reduced AMP production. Our findings identified OPN as a novel regulatory factor of AMP production to modulate bacterial loads and composition of gut microbiota, in turn affecting sepsis outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Intestinal flora promotes the pathogenesis of colorectal cancer (CRC) through microorganisms and their metabolites. This study aimed to investigate the composition of intestinal flora in different stages of CRC progression and the effect of fecal microbiota transplantation (FMT) on CRC mice. Methods: The fecal microbiome from healthy volunteers (HC), colorectal adenoma (CRA), inflammatory bowel disease (IBD), and CRC patients were analyzed by 16s rRNA gene sequencing. In an azoxymethane (AOM)/dextran-sulfate-sodium (DSS)-induced CRC mouse, the effect of FMT from HC, CRA, CRC, and IBD patients on CRC mice was assessed by histological analysis. Expression of inflammation- EMT-associated proteins and Wnt/β-catenin pathway were assessed using qRT-PCR and western blot. The ratio of the fecal microorganisms and metabolomics alteration after FMT were also assessed. Result: Prevotella, Faecalibacterium, Phascolarctobacterium, Veillonella, Alistipes, Fusobacterium, Oscillibacter, Blautia, and Ruminococcus abundance was different among HC, IBD, CRC, and CRA patients. HC-FMT alleviated disease progression and inflammatory response in CRC mice, inhibited splenic T help (Th)1 and Th17 cell numbers, and suppressed the EMT and Wnt/β-catenin pathways in tumor tissues of CRC mice. IBD-FMT, CRA-FMT, and CRC-FMT played deleterious roles; the CRC-FMT mice exhibited the most malignant phenotype. Compared with the non-FMT CRC mice, Muribaculaceae abundance was lower after FMT, especially lowest in the IBD-FMT group; while Lactobacillus abundance was higher after FMT and especially high in HC-FMT. Akkermansia and Ileibacterium abundance increased after FMT-HC compared to other groups. Metabolite correlation analysis revealed that Muribaculaceae abundance was significantly correlated with metabolites such as Betaine, LysoPC, and Soyasaponin III. Lactobacillus abundance was positively correlated with Taurocholic acid 3-sulfate, and Ileibacterium abundance was positively correlated with Linoleoyl ethanolamide. Conclusion: The different intestinal microbiota communities of HC, IBD, CRA, and CRC patients may be attributed to the different modulation effects of FMT on CRC mice. CRC-FMT promoted, while HC-FMT inhibited the progress of CRC. Increased linoleoyl ethanolamide levels and abundance of Muribaculaceae, Akkermansia, and Ileibacterium and reduced Fusobacterium might participate in inhibiting CRC initiation and development. This study demonstrated that FMT intervention could restore the intestinal microbiota and metabolomics of CRC mice, suggesting FMT as a potential strategy for CRC therapy. [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]

ABSTRACT Objective Method Results Discussion Avoidant/restrictive food intake disorder (ARFID) is an eating disorder characterized by a severely restrictive diet leading to significant physical and/or psychosocial sequelae. Largely owing to the phenotypic heterogeneity, the underlying pathophysiological mechanisms are relatively unknown. Recently, the communication between microorganisms within the gastrointestinal tract and the brain—the so‐called microbiota‐gut‐brain axis—has been implicated in the pathophysiology of eating disorders. This Spotlight review sought to investigate and conceptualize the possible ways that the microbiota‐gut‐brain axis is involved in ARFID to drive future research in this area.By relating core symptoms of ARFID to gut microbiota and its signaling pathways to the brain, we evaluated how the gut microbiota is potentially involved in the pathophysiology of ARFID.We hypothesized that the restricted type and amount of food intake characteristic of ARFID diminishes gut microbial diversity, including beneficial bacteria and their metabolites capable of signaling to the brain, to modulate biopsychological pathways relevant to ARFID: homeostatic signaling, food reward, interoception, sensory sensitivity, disgust, perseveration, fear‐based learning, and mood. Candidate signaling mechanisms include microbial‐induced effects on inflammation, cortisol, and neurotransmitters such as dopamine and serotonin.Through reviewing the extant evidence, we conceptualized a new theoretical framework of ARFID with an emphasis on microbiota‐gut‐brain axis signaling to inform future research. Although more research is necessary to evaluate this theoretical model, the tentative evidence suggests that therapeutics specifically targeting the gut microbiota for the treatment of ARFID symptomatology warrants more investigation. [ABSTRACT FROM AUTHOR]

The gut microbiota influences multiple aspects of human health and disease. Several studies have indicated an association between the gut microbiota and response to immune checkpoint inhibitors in various cancers, but there is scarce data from breast cancer. The randomized ALICE trial demonstrated improved progression‐free survival (PFS) from adding the programmed cell death 1 ligand 1 (PD‐L1) inhibitor atezolizumab (atezo) to immunomodulating chemotherapy (chemo) in metastatic triple‐negative breast cancer (mTNBC), even for PD‐L1negative disease. Herein, we investigated the microbiota composition and dynamics in the ALICE patients and their association with clinical outcome, by analyzing fecal samples collected at baseline and after 8 weeks. We applied 16S (V3‐V4) rRNA sequencing to characterize the diversity and taxonomic composition. Kaplan–Meier and Cox proportional hazard models were used for time‐to‐event analyses. We found that high alpha diversity by Faith's phylogenetic diversity (PD) at baseline was associated with prolonged PFS in the total study population and in the atezo‐chemo arm, but not in the placebo‐chemo arm. Moreover, Faith's PD appeared to be predictive of benefit from atezolizumab. Patients with high Faith's PD exhibited a PFS hazard ratio of 0.34 (P = 0.018) in favor of the atezo‐chemo arm, compared to 0.83 (P = 0.62) in the low Faith's PD group. Faith's PD was significantly reduced during treatment. At baseline, Bifidobacterium was significantly overrepresented in patients without clinical benefit in the atezo‐chemo arm, but not in the placebo‐chemo arm. These findings suggest that alpha diversity by Faith's PD should be further investigated as a prognostic and predictive biomarker in patients with mTNBC receiving chemo‐immunotherapy. [ABSTRACT FROM AUTHOR]