The gut microbiota plays a crucial role in human health, but its impact on lipid metabolism remains unclear. Understanding the causal relationship between gut bacteria and lipid profiles is essential for developing strategies to prevent and treat dyslipidemia and cardiovascular diseases. This study aimed to assess this relationship using two-sample Mendelian randomization (MR). Data for both exposure and outcomes were obtained from the IEU-GWAS database, with lipid profile data sourced from a publication. Genome-wide significant single nucleotide polymorphisms (SNPs), which were independent of outcome factors but correlated with exposure variables, were identified as instrumental variables. Several MR methods, including weighted analysis, maximum likelihood, inverse variance weighting (IVW), MR-Egger, and weighted median, were applied. Colocalization analysis further validated the findings. The analysis revealed microbial groups with causal relationships to ApoA1, ApoB, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, and triglycerides. Reverse MR and colocalization analysis provided additional confirmation of these results. This study offers new evidence of the causal link between gut microbiota and lipid profiles, providing insights for improving lipid profiles and reducing cardiovascular disease risk.

Epigallocatechin-3-gallate (EGCG), a major catechin in green tea, exhibits potent antioxidant and disease-preventive properties, but its application is limited by poor stability and bioavailability. This study aimed to address these challenges by preparing and characterizing three EGCG-loaded nanoparticles: chitosan-EGCG-tripolyphosphate nanoparticles (CE-NPs), β-cyclodextrin-EGCG (BE-NPs), and EGCG-nanostructured lipid carriers (NE-NPs). BE-NPs exhibited the highest loading performance and retention rate under thermal environment (89.78 % after 10 h at 80 °C). NE-NPs had the highest EGCG stability in alkaline condition (45 % after 4 h at pH 7.4). Compared to free EGCG, all NPs significantly improved in vitro bioaccessibility following incubation in simulated gastrointestinal digestion for 4 h; BE-NPs enhanced oral bioavailability by 1.71 times in vivo. Additionally, CE-NPs and NE-NPs increased the relative abundance of Faecalibaculum, Erysipelotrichaceae, and Bifidobacterium in the colons of Sprague-Dawley rats. These findings suggest that BE-NPs are a promising nano-delivery system for enhancing EGCG stability and bioavailability in healthy organisms.

Gut microbiota dysbiosis induced by antibiotic use weakens its colonization resistance against opportunistic pathogens, increasing the risk of invasion and infection. While probiotics have the potential to restore the impaired gut microbial structure and prevent respiratory tract infections, the effectiveness of specific strains and the underlying mechanisms remain largely unexplored. In this study, the preventive effects of a novel butyrate-producing bacterium, Clostridium cellabutyricum YQ-FP-027T against Pseudomonas aeruginosa infection after antibiotic exposure were investigated in antibiotic-pretreated mice model.

Phenotypic characterizations including the bacterial load in the lung, the assessment of gene expression of immune factors in lung tissue using qPCR, and detection of gut microbial composition using 16S rRNA sequencing were conducted. Pulmonary bacterial load and expression levels of immune factors of lung tissue, and gut microbial composition were evaluated.

Our results demonstrated that YQ-FP-027T ameliorated lung tissue integrity, significantly reduced pulmonary bacterial burden, and decreased the expression of interleukin-1β and TNF-α, while enhancing the expression of interleukin-10 and cathelicidin-related antimicrobial peptide. Furthermore, YQ-FP-027T increased the abundance of Lachnospiraceae in the gut and reduced the abundance of opportunistic pathogens such as Enterococcaceae and Helicobacteraceae.

These results suggest YQ-FP-027T exerts probiotic effects by restoring gut microbiota balance, enhancing intestinal barrier function, and positively influencing pulmonary immune responses through the gut-lung axis. This study reveals the preventive potential of YQ-FP-027T against P. aeruginosa infection in the context of gut microbiota dysbiosis, offering a novel preventive strategy.

Micro- and nanoplastics (MNPLs) are emerging environmental pollutants that have garnered significant attention over the past few decades due to their detrimental effects on human health through various exposure pathways. This study investigates the impact of MNPLs on gut microbiota, utilizing Drosophila melanogaster as a model organism. Drosophila was selected for its microbiota's similarities to humans and its established role as an accessible and well-characterized model system. To analyze microbiota, full-length 16S rRNA gene sequencing was performed using the Nanopore sequencing platform, enabling comprehensive profiling of the microbial populations present in the samples. As models of MNPLs, two commercial polystyrene nanoplastics (PS-NPLs, 61.20 and 415.22 nm) and one lab-made polylactic acid nanoplastic (PLA-NPLs, 463.90 nm) were selected. As a positive control, zinc oxide nanoparticles (ZnO-NPs) were used. The observed findings revealed that exposure to MNPLs induced notable alterations in gut microbiota, including a reduction in bacterial abundance and shifts in species composition. These results suggest that MNPLs exposure can lead to microbial dysbiosis and potential gut health disruptions through its interaction, either with the gut epithelial barrier or directly with the resident microorganisms.

The use of antibiotics unbalances the intestinal microbiota. Probiotics, prebiotics, and synbiotics are alternatives for these unbalances. The effects of a new synbiotic composed of probiotic Saccharomyces boulardii CNCM I-745 and fructans from Agave salmiana (fAs) as prebiotics were assessed to modulate the intestinal microbiota. Two probiotic presentations, the commercial probiotic (CP) and the microencapsulated probiotic (MP) to improve those effects, were used to prepare the synbiotics and feed Wistar rats subjected to antibiotics (AB). Eight groups were studied, including five controls and three groups to modulate the microbiota after the use of antibiotics: G5: AB + MP-synbiotic, G6: AB + CP-synbiotic, and G8: AB + fAs. All treatments were administered daily for 7 days. On days 7 and 21, euthanasia was performed, cecum tissue was recovered and used to evaluate histological analysis and to study microphotograph by TEM, and finally, bacterial DNA was extracted and 16S rRNA gene metabarcode sequencing was performed. Histological analysis showed less epithelial damage and more abundance of the intestinal microbiota in the groups G5, G6, and G8 in comparison with the AB control group after 7 days. Microphotograph of the cecum at 2 weeks post treatment showed that G5 and G6 presented beneficial effects in epithelial reconstruction. Interestingly, in the groups that used the synbiotic without AB (G3 and G4) in addition to contributing to the recovery of the autochthonous microbiota, it promotes the development of beneficial microorganisms; those results were also achieved in the groups that used the synbiotic with AB enhancing the bacterial diversity and regulating the impact of AB.

Microplastics are recognised as ubiquitous pollutants as they are now found in all terrestrial and marine ecosystems. The interactions between microbiota and microplastics are an issue of fundamental importance in studying and maintaining global health. Microplastics alter the structures and functions of microbial communities, resulting in adverse health effects. A comprehensive understanding of these effects through interdisciplinary research is essential to mitigate pollution and protect the health of ecosystems. The review aims to explore these interactions within a One Health framework. Indeed, a deeper understanding of the processes involved in the interaction between microbiota and microplastics could pave the way for new and promising strategies to mitigate the harmful effects of microplastics on ecosystems and human health.

Selenium-enriched tea represents an ideal source of selenium supplements, yet its effects on mice with intestinal disorders remain under-documented. Therefore, we have carried out relevant research.

We determined the main chemical components of selenium-enriched green tea and evaluated the antioxidant and anti-inflammatory effects of selenium-enriched green tea extract and changes in intestinal flora of antibiotic-induced intestinal disease mice through BALB/c mouse experiments.

The main chemical components of selenium-enriched green tea and green tea are significantly different. Selenium-enriched green tea is characterized by a high selenium content, with tea polyphenols, flavonoids, tea polysaccharides and catechins being the primary constituents. The results of animal experiments indicate that the extract of green tea rich in selenium increased the content of antioxidant factors in the intestines of mice and reduced the levels of intestinal inflammatory factors. This was also confirmed by mRNA gene expression determination. In addition, selenium-enriched green tea extracts can reduce the weight loss and intestinal pathological damage induced by antibiotics, promote the colonization of Bifidobacterium and Lactobacillus in the intestinal tract of mice and inhibit the growth of Escherichia coli and Enterococcus in the intestinal tract.

Selenium-enriched green tea has high nutritional content. It demonstrates superior potential in alleviating oxidative stress and inflammatory responses caused by intestinal diseases, and plays a role in regulating the intestinal flora. © 2025 Society of Chemical Industry.

Malignant ascites is a common complication of advanced ovarian cancer (OC) and gastrointestinal cancer (GI), significantly impacting metastasis, quality of life, and survival. Increased intestinal permeability can lead to blood or lymphatic infiltration and microbial translocation from the gastrointestinal or uterine tract. This study aimed to identify microbiota-derived metabolites in ascites from OC (stages II-III and IV) and GI patients, assessing their roles in tumor progression.

Malignant ascites samples from 18 OC and GI patients were analyzed using a four-dimensional (4D) untargeted metabolomics approach combining reversed-phase (RP) and hydrophilic interaction liquid chromatography (HILIC) with trapped ion mobility spectrometry time-of-flight mass spectrometry (timsTOF-MS). Additonally, a targeted flow cytometry-based cytokine panel was used to screen for inflammatory markers. Non-endogenous, microbiota-derived metabolites were identified through the Human Microbial Metabolome Database (MiMeDB).

OC stage IV exhibited metabolic profiles similar to GI cancers, while OC stage II-III differed significantly. Stage IV OC patients exhibited higher levels of 11 typically microbiome-derived metabolites, including 1-methylhistidine, 3-hydroxyanthranilic acid, 4-pyridoxic acid, biliverdin, butyryl-L-carnitine, hydroxypropionic acid, indole, lysophosphatidylinositol 18:1 (LPI 18:1), mevalonic acid, N-acetyl-L-phenylalanine, and nudifloramide, and lower levels of 5 metabolites, including benzyl alcohol, naringenin, o-cresol, octadecanedioic acid, and phenol, compared to stage II-III. Correlation analysis revealed positive associations between IL-10 and metabolites such as glucosamine and LPCs, while MCP-1 positively correlated with benzyl alcohol and phenol.

4D metabolomics revealed distinct metabolic signatures in OC and GI ascites, highlighting microbiota-derived metabolites involved in lipid metabolism and inflammation. Metabolites like 3-hydroxyanthranilic acid, indole, and naringenin may serve as markers of disease progression and underscore the microbiota's role in shaping malignant ascites and tumor biology.

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

Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease. Glycyrrhiza pallidiflora polysaccharide (GPP) is an important constituent of a species of Glycyrrhiza pallidiflora, but its therapeutic mechanism in UC mice is not clear. A dextran sulphate sodium salt (DSS)-induced mouse model of UC was established, and GPP was extracted by ultrasound-assisted extraction, optimised to a GPP content of 25.66% by one-factor optimisation. The effects of different doses (100, 200, 300 mg/kg) of GPP on UC were investigated. The results showed that GPP could delay the trend of weight loss, reduce the DAI score and decrease colon damage in mice, and GPP had a better ameliorative effect on enteritis, which provided a theoretical basis for studying the effect of natural products on UC.

Frailty is an ageing-associated geriatric syndrome that severely affects the functional status, quality of life and life expectancy of older adults. Immune dysfunction and chronic inflammation play crucial roles in frailty, and this study aimed to explore the correlation between the intestinal microbiota and frailty.

A cross-sectional survey was conducted using a comprehensive geriatric assessment of older individuals who underwent medical checkups at the Health Management Center from April 2023 to May 2024. A total of 672 older individuals who met the inclusion criteria were included and divided into a healthy control group and a frail case group. Clinical data, as well as blood and stool samples, were collected. The data from the two groups were analysed with 16S rRNA sequencing in 20 and 30 cases, respectively. SPSS 25.0 was used for statistical analysis.

There were significant differences in income, smoking, and globulin levels between the two groups, while there were no differences in age or sex. There was no significant difference in the abundance or species evenness of intestinal bacteria between the two groups. However, the abundance of accessory bacteria, bifidobacteria, and Escherichia coli in the frail group was greater than that in the control group. Specifically, Escherichia-Shigella was significantly upregulated and fit well into the prediction model of frailty.

The gut microbiota of frail older individuals underwent significant changes in structural composition, and the presence of Escherichia-Shigella may be a diagnostic marker for debilitating diseases. These findings provide an essential clinical reference value for developing methods for preventing or alleviating frailty based on specific microbial communities.

Pu-erh tea, a dark tea from China, is classified into raw and ripened types. Both have significant anti-obesity effects. Polyphenols are among their major bioactive components. This study aimed to explore the anti-obesity properties and mechanisms of raw (R-TP) and ripened (F-TP) Pu-erh tea polyphenols.

The results showed that R-TP and F-TP significantly reduced body weight, improved insulin resistance, and enhanced glucose and lipid metabolism in high-fat-diet (HFD)-induced obese mice. Mild differences were observed in their impact on fat metabolism, carbohydrate metabolism, and inflammation levels. Both R-TP and F-TP were able to restore the disrupted intestinal flora caused by HFD treatment, returning them to a composition and levels similar to those of normal mice. Interestingly, the gut microbiota of all the mice could be reclassified into three enterotypes (enterotype Type-1, Type-2, and Type-HFD). Lactobacillaceae predominated in Type-1. Lactobacillaceae, Muribaculaceae, and Lachnospiraceae were the most common in Type-2. Type-HFD was primarily composed of Atopobiaceae, Lachnospiraceae, Lactobacillaceae, Ruminococcaceae, and Erysipelotrichaceae. The small differences in the effects of R-TP and F-TP may be due to variations in enterotypes.

These findings indicate that R-TP and F-TP can alleviate obesity by regulating the enterotype of gut microbiota, suggesting that they possess the potential for application in the treatment of obesity and the development of anti-obesity agents. © 2025 Society of Chemical Industry.

Given the complex relationship between the gut microbiome and chronic kidney disease (CKD), exploring the potential role and scope of microbiota-targeted therapies in pediatric CKD is highly relevant. We aim to provide an overview of gut-targeted therapeutic strategies, including nutritional interventions (fiber, phytochemicals, fermented foods, and traditional Chinese medicines), probiotics, synbiotics, oral absorbents, and fecal microbial transplantation. Enhancing physical activity and preventing constipation are additional strategies that may promote gut microbiome health. In a uremic environment, gut microbiota-targeted therapies could potentially rebalance the gut microbiota, improve gut barrier function, decrease uremic toxin concentrations, enhance the production of short-chain fatty acids (SCFA), and reduce inflammation. While research in adult CKD patients has provided insights into these approaches, there are limited data in children with CKD. This review aims to summarize potential targeted therapies for restoring a balanced gut microbiota, emphasizing the need for studies that evaluate their effects on clinical outcomes in pediatric CKD.

Decades of research have made clear that host-associated microbiomes touch all facets of health. However, effective therapies that target the microbiome have been elusive given its inherent complexity. Here, we experimentally examined diet-microbe-host interactions through a complex systems framework, centered on dietary oxalate. Using multiple, independent molecular, rodent, and in vitro experimental models, we found that microbiome composition influenced multiple oxalate-microbe-host interfaces. Importantly, the administration of the oxalate-degrading specialist, Oxalobacter formigenes, was only effective against a poor oxalate-degrading microbiota background and gives critical new insights into why clinical intervention trials with this species exhibit variable outcomes. Data suggest that, while heterogeneity in the microbiome impacts multiple diet-host-microbe interfaces, metabolic redundancy among diverse microorganisms in specific diet-microbe axes is a critical variable that may impact the efficacy of bacteriotherapies, which can help guide patient and probiotic selection criteria in probiotic clinical trials.

Obesity is recognized as a global epidemic that can result in changes in the human body and metabolism. Accumulating evidence indicates that gut microbiota (GM) can affect the development of obesity. The GM not only plays a crucial role in digesting and absorbing nutrients, but also in maintaining the overall health of the host. Dietary supplements such as non-starch polysaccharides are mainly fermented by the GM in the colon. Recent findings suggest that shaping the GM through the prebiotic function of non-starch polysaccharides may be a viable strategy against obesity. In this paper, the effects of non-starch polysaccharides on host health, together with their prebiotic function influencing the GM to control obesity via the gut-target organ axis, are reviewed. Potential perspectives of non-starch polysaccharides exhibiting anti-obesity effects via the gut-target organ axis are proposed for future research.

Schistosomiasis japonica is a parasitic disease that seriously endangers human health. Patients with advanced Schistosoma japonicum infection often suffer from cirrhosis and portal hypertension. Splenectomy has been widely used in the treatment of these patients. Previous studies have confirmed that S. japonicum infection is closely related to the gut microbiota, but the impact of splenectomy on the gut microbiota of patients with advanced S. japonicum infection remains unclear. This study used 16sRNA sequencing technology to compare the differences in intestinal flora between patients with advanced S. japonicum infection who underwent splenectomy and non-surgical patients. We focused on the changes in the species composition, diversity and functions of the intestinal flora. Our study shows that dysbiosis of the gut microbiome occurred in patients with advanced S. japonicum infection, including changes in abundance and diversity and the disorder of biological function. The intestinal flora structure, diversity and function of patients who underwent splenectomy were significantly changed compared with those who did not undergo surgery.

Diet modulates gut microbiome composition and function. However, determining causal links between diet-gut microbiome interactions and human health is complicated by inconsistencies in the evidence, arising partially from variability in research methods and reporting. Widespread adoption of standardized best practices would advance the field but require those practices to be identified, consolidated, and discussed. This umbrella review aimed to identify recommended best practices, define existing gaps, and collate considerations for conducting research on diet-gut microbiome interactions and their impact on human health outcomes. Reviews meeting inclusion criteria and published after 2013 were identified using a systematic search. Recommendations, considerations, and gaps relating to the best practices associated with study design, participant selection, dietary intervention/assessment, biological sample collection, and data analysis and reporting were extracted and consolidated. Eight narrative reviews were included. Several general points of agreement were identified, and a recurring theme was that best practices are dependent upon the research aims, outcomes, and feasibility. Multiple gaps were also identified. Some, such as suboptimal diet assessment methods and lack of validated dietary intake biomarkers, are particularly relevant to nutrition science. Others, including defining a "healthy" gut microbiome and the absence of standardized sample and data collection/analysis protocols, were relevant specifically to gut microbiome research. Gaps specific to diet-gut microbiome research include the underrepresentation of microbiome-modulating dietary components in food databases, lack of knowledge regarding interventions eliciting changes in the gut microbiome to confer health benefits, lack of in situ measurement methods, and the need to further develop and refine statistical approaches for integrating diet and gut microbiome data. Future research and cross-disciplinary exchange will address these gaps and evolve the best practices. In the interim, the best practices and considerations discussed herein, and the publications from which that information was extracted provide a roadmap for conducting diet-gut microbiome research. This trial was registered at PROSPERO as CRD42023437645.

Rheumatoid arthritis is a chronic autoimmune disorder characterized by destructive, symmetric joint inflammation and synovitis, resulting in substantial disability that profoundly compromises patients' quality of life. Its pathogenesis encompasses complex interactions between genetic and environmental factors. Recent advances in bacterial DNA sequencing technologies have uncovered a significant correlation between the human gut microbiota composition and rheumatoid arthritis progression. Growing clinical and experimental evidence establishes the gut-joint axis as a crucial mediator in rheumatoid arthritis pathogenesis. Comprehensive investigation of gut microbial communities and their metabolites' influence on rheumatoid arthritis mechanisms, coupled with the elucidation of microbiome's bidirectional regulatory effects in disease development, not only deepens our understanding of pathological processes but also establishes a theoretical framework for developing novel diagnostic biomarkers and personalized therapeutic interventions to enhance patient outcomes.

Cardiovascular diseases (CVDs), including heart failure (HF), hypertension, myocardial infarction (MI), and atherosclerosis, are increasingly linked to gut microbiota dysbiosis and its metabolic byproducts. HF, affecting over 64 million individuals globally, is associated with systemic inflammation and gut barrier dysfunction, exacerbating disease progression. Similarly, hypertension and MI correlate with reduced microbial diversity and an abundance of pro-inflammatory bacteria, contributing to vascular inflammation and increased cardiovascular risk. Atherosclerosis is also influenced by gut dysbiosis, with key microbial metabolites such as trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFAs) playing crucial roles in disease pathogenesis. Emerging evidence highlights the therapeutic potential of natural compounds, including flavonoids, omega-3 fatty acids, resveratrol, curcumin, and marine-derived bioactives, which modulate the gut microbiota and confer cardioprotective effects. These insights underscore the gut microbiota as a critical regulator of cardiovascular health, suggesting that targeting dysbiosis may offer novel preventive and therapeutic strategies. Further research is needed to elucidate underlying mechanisms and optimize microbiome-based interventions for improved cardiovascular outcomes.

From a biological point of view, Diversity, Equity, and Inclusion (DEI) are important at multiple levels, which include our genetics, microbiomes, diets, and all organ system interactions. Considering only DEI's sociological aspects is equivalent to the error of "throwing out the baby with the bath water." Variances in microbial diversity within our microbiomes might affect our health through systemic interactions affecting metabolites, maintaining immune homeostasis, and wound healing of cellular damage from an infection, physical stress, or psychological trauma. An imbalance of our immune cell subsets, both innate and adaptive, and the microbes in any of our microbiomes might lead to more cellular damage from excessive inflammation and oxidative stress and less immune regulation. The immune dysregulation may occur due to the loss of endometrial barriers enabling the spread of microbes, environmental pollutants, and allergens. Heat waves, sleep deprivation, and increased prevalence of pollutants such as polychlorinated biphenyls, which weaken endothelial barriers, may be responsible for the enhanced prevalence of physical and psychological stresses. Leakage of our useful gut microbiota into the periphery might initiate inflammatory responses, and an altered gut microbiome might affect the gut-brain axis that influences physical and mental health.

Eurotium cristatum (EC), the dominant fungus in Fuzhuan brick tea, has significant applications in food fermentation and pharmaceutical industries, exhibiting probiotic properties, but further investigation of its intestinal benefits is required. This study characterized the EC-520 strain through whole genome sequencing and evaluated its effects on rat colons using histomorphology, 16S rRNA sequencing, and untargeted metabolomics. The genomic analysis revealed that EC-520 possessed a 28.37 Mb genome distantly related to Aspergillus flavus. The 16S results demonstrated that EC-520 significantly increased the abundance of Bacteroidota (p < 0.05) while decreasing the Proteobacteria and Firmicutes/Bacteroidota ratio (the F/B ratio); at the genus level, it elevated Muribaculaceae and Clostridia_UCG-014 while reducing harmful bacteria. The metabolomic results showed that EC-520 also significantly altered tryptamine, caproic acid, isocaproic acid, and erucic acid (p < 0.05). Additionally, the Spearman's correlation analysis revealed that Muribaculaceae_unclassified and Clostridia_UCG-014_unclassified were significantly positively correlated with tryptamine, caproic acid, isocaproic acid, and erucic acid. Therefore, this study suggested that EC-520 enhanced the colon barrier and increased the abundance of Muribaculaceae_unclassified and Clostridia_UCG-014_unclassified, thus promoting the secretion of tryptamine and affecting the release of 5-hydroxytryptamine (5-HT). It also promoted the secretion of certain fatty acids, enhancing the balance of the colonic microbiota. This study provides a new view for a comprehensive understanding of EC's regulatory role in the colon.

Alzheimer's disease (AD) has emerged as a global public health priority characterized by escalating prevalence and the limited efficacy of current therapeutic approaches. Although the pathological complexity of AD is well-recognized, its underlying etiology remains incompletely elucidated. Current research highlights a bidirectional gut-brain axis (GBA) interaction, wherein gut microbiome perturbations may impair intestinal barrier stability, influence immune responses, and blood-brain barrier permeability through microbial metabolite-mediated pathways, thereby contributing to AD pathophysiology. Notably, probiotics demonstrate therapeutic potential by restoring gut microbiome homeostasis, reinforcing intestinal barrier integrity, and mitigating neuroinflammatory responses via GBA. This review focuses on investigating the gut microbiome alterations in AD pathogenesis, the interaction of probiotics with GBA, and its significance in AD pathogenesis. By synthesizing current clinical evidence, this review aims to establish a scientific foundation for probiotic-based interventions as a novel therapeutic strategy in AD management.

While growing evidence highlights the role of gut microbiota and inflammatory proteins in cancer, with cancer-related inflammation now considered the seventh hallmark of cancer, the direct causal relationships between specific microbiota, cancer, and the potential mediating effects of inflammatory proteins have not been fully established.

We employed Mendelian randomization (MR) to assess the causal relationships between gut microbiota, inflammatory proteins, and eighteen distinct cancers using data from extensive genome-wide association studies (GWAS). The primary statistical method utilized was inverse variance weighting (IVW). We also investigated whether inflammatory proteins could mediate the effects of gut microbiota on cancer development.

Our findings revealed 42 positive and 49 inverse causal impacts of gut microbiota on cancer risk (P < 0.05). Additionally, we identified 32 positive and 28 inverse causal relationships between inflammatory proteins and cancer risk. Moreover, genus Collinsella decreased the risk of lung cancer by decreasing levels of T-cell surface glycoprotein CD5 (mediating effect = 16.667%), while genus Ruminococcaceae UCG005 increased the risk of mesothelioma by increasing levels of CCL4 (mediating effect = 5.134%).

Our study provides evidence for a causal association between gut microbiota, inflammatory proteins, and eighteen different cancer types. Notably, the T-cell surface glycoprotein CD5 and CCL4 were identified as mediators linking the genus Collinsella with lung cancer and the genus Ruminococcaceae UCG005 with mesothelioma, respectively.

Huangqin Decoction (HQD), a traditional Chinese medicine (TCM) formula documented in Shang Han Lun, has demonstrated safety and efficacy in the treatment of ulcerative colitis (UC). Recent studies also suggest that HQD exerts therapeutic effects on colorectal cancer (CRC). However, the underlying mechanisms remain unclear.

This study aimed to investigate the therapeutic effects of HQD on CRC and explore its potential mechanisms of action.

The active ingredients and potential targets of HQD were identified through network pharmacology-based analyses. The CRC-related targets were compared with those of HQD. Shared targets were subjected to Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and a protein-protein interaction (PPI) network was constructed. Additionally, APCmin/+ mice were treated with 0.2 % deoxycholic acid (DCA) and gavaged with low or high doses of HQD. Tumor morphology was assessed using hematoxylin and eosin (HE) staining. Immunohistochemical staining was performed to evaluate the expression of Ki-67, Caspase-3, and MUC2 in the intestine. Periodic acid-Schiff (PAS) and PAS-alcian blue (PAS-AB) staining were utilized to detect mucin distribution and the number of goblet cells in the intestines of the mice. The mRNA expression levels of interleukin 6 (IL-6), mitogen-activated protein kinase 8 (MAPK8), vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), albumin (ALB), and Caspase 3 (CASP3) were quantified using quantitative reverse-transcription PCR (qRT-PCR). Immunofluorescence was employed to assess the degree of apoptosis. Additionally, 16S ribosomal RNA gene sequencing, sequence curation and annotation, and metagenomic sequencing were performed to analyze changes in the composition of the mouse intestinal microbiota and related functions and signaling pathways.

The active ingredients of HQD were identified. GO and KEGG pathway enrichment analyses indicated that the shared targets were primarily involved in tumor suppression. HQD effectively treated DCA-induced CRC in mice. Furthermore, positive PAS and PAS-AB staining was significantly increased in the intestines of mice treated with HQD. HQD enhanced the abundance of Lachnospiraceae, Firmicutes, Fusobacteria, and Clostridium, while reducing the abundance of Eggerthellales. Additionally, HQD modulated secondary bile acid metabolism, carbohydrate synthesis, and other energy metabolism pathways, which may underlie its therapeutic effects.

HQD effectively treated CRC in mice, and its mechanisms of action may be related to the regulation of the gut microbiota.

Systemic hypertension is a major risk factor for cardiovascular disease and remains challenging to manage despite the widespread use of antihypertensive medications and lifestyle modifications. This review explores the role of gut microbiota in hypertension development and regulation, highlighting key mechanisms such as inflammation, gut-brain axis modulation, and bioactive metabolite production. We also assess the potential of microbiota-targeted therapies for hypertension management.

Emerging evidence indicates that microbial dysbiosis, high-salt diets, and gut-derived metabolites such as short-chain fatty acids (SCFAs) and bile acids significantly influence blood pressure regulation. Preclinical and early clinical studies suggest that interventions targeting gut microbiota, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), and dietary modifications, may help modulate hypertension. However, variability in gut microbiota composition among individuals and limited human trial data pose challenges to translating these findings into clinical practice. While microbiota-based therapies show promise for hypertension management, further research is needed to establish their efficacy and long-term effects. Large-scale, standardized clinical trials are crucial for understanding the therapeutic potential and limitations of gut microbiota interventions. A deeper understanding of the gut-hypertension axis could lead to novel, personalized treatment strategies for hypertension.

Endometriosis (EM) and adenomyosis (AM) are interrelated gynecological disorders characterized by the aberrant presence of endometrial tissue and are frequently linked with chronic pelvic pain and infertility, yet their pathogenetic mechanisms remain largely unclear. In this cross-sectional study, we analyzed endometrial samples from 244 participants, split into 91 EM patients, 56 AM patients, and 97 healthy controls (HC). We conducted untargeted liquid chromatography-mass spectrometry (LC-MS) and 5R 16S rRNA sequencing to examine endometrial metabolome and microbiome profiles. Additionally, we integrated transcriptomic analysis using nine transcriptomic data sets to investigate the biological basis of these conditions. Metabolomic profiling and 16S rRNA sequencing revealed distinct metabolic and microbial signatures. Specific pathways, including linoleic acid and glycerophospholipid metabolism, show significant alterations in both conditions. Notably, four metabolites, including phosphatidylcholine 40:8 [PC(40:8)], exhibited marked changes in both EM and AM, suggesting shared pathological features. Furthermore, taxonomic analysis identified unique bacterial species associated with each condition, particularly those belonging to the phylum Proteobacteria, which correlated with altered metabolic signatures. Machine learning models demonstrated high predictive accuracy for differentiating between AM, EM, and HC based on metabolic and microbial signatures. Integrative analysis with transcriptomic data highlighted distinct pathways related to immune response and signaling transduction for each condition. Our study provides fresh insights into the pathogenesis of AM and EM through a multi-omic approach, suggesting potential inconsistencies in the underlying pathogenetic mechanisms.

Existing research highlighted a connection between endometriosis (EM) and adenomyosis (AM), underscoring their overlapping symptoms and potential shared pathophysiological mechanisms. Although the role of microbiota in inflammatory conditions has been acknowledged, comprehensive investigations into the endometrial microbiota in cases of EM and AM have been limited. Previous studies identified distinct microbial communities associated with these conditions; however, they were constrained by small sample sizes and a lack of integrated analyses of microbiota and metabolomics. Furthermore, the ongoing debate over whether EM and AM should be classified as separate diseases or related phenotypes emphasizes the necessity for further exploration of their molecular interactions. Our study uncovers distinct microbial and metabolic signatures associated with each condition, revealing both shared and unique pathways that may contribute to their pathogenesis. Furthermore, the integration of transcriptomic data offers valuable insights into the complex interactions underlying these disorders.

Trillions of microorganisms play a pivotal role in maintaining health and preventing disease in humans. Their presence influences daily life, habits, energy levels, and pathologies. The present narrative review synthesized recent studies of microbial diversity across organ systems. The composition of the microbiota regulates the intestinal barrier, modulates the immune response, influences metabolism, and produces essential compounds such as short-chain fatty acids and neurotransmitters. Dysbiosis is associated with numerous pathologies, including metabolic, autoimmune, neurodegenerative, and cardiovascular diseases. The microbiota is key to maintaining physiological balance and reducing disease risk. Therapeutic interventions, such as probiotics, prebiotics, postbiotics, and microbiome transplantation, offer promising perspectives in restoring microbial homeostasis and preventing chronic diseases.

Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, arise from various factors such as dietary, genetic, immunological, and microbiological influences. The gut microbiota plays a crucial role in the development and treatment of IBD, though the exact mechanisms remain uncertain. Current research has yet to definitively establish the beneficial effects of the microbiome on IBD. Bacteria and viruses (both prokaryotic and eukaryotic) are key components of the microbiome uniquely related to IBD. Numerous studies suggest that dysbiosis of the microbiota, including bacteria, viruses, and bacteriophages, contributes to IBD pathogenesis. Conversely, some research indicates that bacteria and bacteriophages may positively impact IBD outcomes. Additionally, plant metabolites play a crucial role in alleviating IBD due to their anti-inflammatory and microbiome-modulating properties. This systematic review discusses the role of the microbiome in IBD pathogenesis and evaluates the potential connection between plant metabolites and the microbiome in the context of IBD pathophysiology.

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by joint inflammation and skin lesions. Recent research has underscored the critical role of gut microbiota-comprising bacteria, fungi, viruses, and archaea-in the pathogenesis and progression of PsA. This narrative review synthesizes the latest findings on the influence of gut microbiota on PsA, focusing on mechanisms such as immune modulation, microbial dysbiosis, the gut-joint axis, and its impact on treatment. Advances in high-throughput sequencing and metagenomics have revealed distinct microbial profiles associated with PsA. Studies show that individuals with PsA have a unique gut microbiota composition, differing significantly from healthy controls. Alterations in the abundance of specific bacterial taxa, including a decrease in beneficial bacteria and an increase in potentially pathogenic microbes, contribute to systemic inflammation by affecting the intestinal barrier and promoting immune responses. This review explores the impact of various factors on gut microbiota composition, including age, hygiene, comorbidities, and medication use. Additionally, it highlights the role of diet, probiotics, and fecal microbiota transplantation as promising strategies to modulate gut microbiota and alleviate PsA symptoms. The gut-skin-joint axis concept illustrates how gut microbiota influences not only gastrointestinal health but also skin and joint inflammation. Understanding the complex interplay between gut microbiota and PsA could lead to novel, microbiome-based therapeutic approaches. These insights offer hope for improved patient outcomes through targeted manipulation of the gut microbiota, enhancing both diagnosis and treatment strategies for PsA.

Doxorubicin is a widely used chemotherapy for the treatment of several types of cancer. However, its application is restricted due to adverse effects, particularly cardiotoxicity, which can progress to heart failure-a chronic and debilitating condition. Several mechanisms have been identified in the pathophysiology of doxorubicin-induced cardiotoxicity, including oxidative stress, mitochondrial dysfunction, inflammation, and disruption of collagen homeostasis. More recently, dysbiosis of the gut microbiota has been implicated in the development and perpetuation of cardiac injury. Studies have reported alterations in the composition and abundance of the microbiota during doxorubicin treatment. Therefore, as of recent, there is a new field of research in order to develop strategies involving the gut microbiota to prevent or attenuate cardiotoxicity since there is no effective therapy at the moment. This narrative review aims to provide an update on the role of gut microbiota and intestinal permeability in the pathophysiology of cardiovascular diseases, and more specifically doxorubicin-induced cardiotoxicity. Additionally, it seeks to establish a foundation for future research targeting gut microbiota to alleviate cardiotoxicity.

The pathogenesis of non-organic anorexia in children is not clear. This study intends to analyze intestinal bacteria to provide a relevant theoretical basis for the clinical rational selection of microecological agents. In the present study, children with non-organic anorexia were included in the anorexia group and normal healthy children in the control group. Stool samples were collected for the bioinformatics analysis after PCR and high-throughput sequencing. The results showed that the Ace, Chao, and Shannon indexes in the anorexia group were higher than those in the control group, while the Simpson index in the control group was lower than in the anorexia group. There were 14 taxa in the anorexia group and 11 taxa in the healthy control group at the phylum level, and 193 taxa in the anorexia group and 180 in the control group at the genus level. The dominant bacteria at the phylum level of the two groups were the same, while there were 16 dominant bacteria taxa in the anorexia group and 17 in the control group at the genus level. The ratio of percentage abundance of Bacteroidetes to that of Firmicutes (the B/F index) in the anorexia group was higher than in the control group. The abundance of Bacteroidetes in the anorexia group was higher than that in the control group, and the abundance of Actinomycetes in the control group was higher than that in the anorexia group. There were significant differences in 14 dominant genera between the two groups at the genus classification level. The LEfSe multilevel species difference analysis showed that at the phylum level, the significant influential bacterial taxa in the anorexia group were Bacteroidetes and Actinobacteria in the control group. At the genus level, the significant influential bacterial taxa in the anorexia group were Bacteroides, Faecalibacterium, and Subdoligranulum, and Bifidobacterium, Blautia, Streptococcus, Lachnoclostridium, and Erysipelatoclostridium in the control group. We conclude that the increase in Bacteroides abundance or in the B/F index and the reduction in Bifidobacterium abundance were related to the pathogenesis of anorexia.

Lactoferrin (Lf) is a multifunctional glycoprotein with well-established antimicrobial, anti-inflammatory, and iron-binding properties. Emerging evidence suggests that Lf also plays a neuroprotective role, particularly in neurodegenerative disorders characterized by protein aggregation, such as Parkinson's disease (PD). Alpha-synuclein (aSyn) aggregation is a pathological hallmark of PD and other synucleinopathies, contributing to neuronal dysfunction and disease progression. Recent studies indicate that Lf may interfere with aSyn aggregation, iron chelation, and modulation of oxidative stress and neuroinflammation. Additionally, Lf's ability to cross the blood-brain barrier and its potential impact on the gut-brain axis highlight its promise as a therapeutic agent. This review explores Lf's mechanisms of action in synucleinopathies, its potential as a disease-modifying therapy, and innovative delivery strategies that could enhance its clinical applicability. By addressing the pathological and therapeutic dimensions of aSyn aggregation, we propose Lf as a compelling candidate for future research and clinical development in neurodegenerative diseases.

Colorectal cancer (CRC) is a prevalent global malignancy with complex etiologies, including microbiota alterations. This study investigates gut microbiota and biofilm-producing bacteria in 35 Thai CRC patients, analyzing paired normal and tumor biopsy samples. Bacterial DNA from the V3-V4 region of 16S rRNA was sequenced, and biofilms were visualized via scanning electron microscopy and fluorescence in situ hybridization (FISH). Results revealed Firmicutes as the dominant phylum, followed by Bacteroidota, Proteobacteria, and Fusobacteriota, with Fusobacteriota and Bacteroidota notably enriched in left-sided CRC. Key biofilm producers-Bacteroides fragilis, Fusobacterium nucleatum, and Pasteurella stomatis-showed significantly higher gene expression in tumor tissues. Dense biofilms and higher Fusobacterium abundance, localized within the crypts of Lieberkuhn, were observed in CRC tissues. These findings highlight CRC-associated microbiota alterations and pathogenic biofilm production, emphasizing a spatial relationship between tumor location and microbial distribution, with potential implications for understanding CRC pathogenesis and therapeutic targeting.

The gut microbiome has emerged as a novel and intriguing focus in mood disorder research. Emerging evidence demonstrates the significant role of the gut microbiome in influencing mental health, suggesting a bidirectional communication between the gut and the brain. This review examines the latest findings on the gut-microbiota-brain axis and elucidates how alterations in gut microbiota composition can influence this axis, leading to changes in brain function and behavior. Although dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation have yielded encouraging results, significant advances are needed to establish next-generation approaches that precisely target the neurobiological mechanisms of mood disorders. Future research must focus on developing personalized treatments, facilitated by innovative therapies and technological progress, which account for individual variables such as age, sex, drug history, and lifestyle. Highlighting the potential therapeutic implications of targeting the gut microbiota, this review emphasizes the importance of integrating microbiota research into psychiatric studies to develop more effective and personalized treatment strategies for mood disorders.

Sleep-disordered breathing (SDB) is characterized by recurrent reductions or interruptions in airflow during sleep, termed hypopneas and apneas, respectively. SDB impairs sleep quality and is linked to substantive health issues including cardiovascular and metabolic disorders, as well as cognitive decline. Recent evidence suggests a link between gut microbiota (GM) composition and sleep apnea. Indeed, GM, a community of microorganisms residing in the gut, has emerged as a potential player in various diseases, and several studies have identified associations between sleep apnea and GM diversity along with shifts in bacterial populations. Additionally, the concept of "leaky gut," a compromised intestinal barrier with potentially increased inflammation, has emerged as another key player in the potential bidirectional relationship between GM and sleep apnea. One of the potential effectors could be extracellular vesicles (EVs) underlying gut-brain communication pathways that are relevant to sleep regulation and function. Thus, therapeutic implications afforded by targeting the GM or exosomes for sleep apnea management have surfaced as promising areas of research. This review explores current understanding of the relationship between GM, exosomes and sleep apnea, highlighting key research dynamics and potential mechanisms. A comprehensive review of the literature was conducted, focusing on studies investigating GM composition, intestinal barrier function and gut-brain communication in relation to sleep apnea.

Metabolic syndrome (MetS) is a complex disorder characterized by a cluster of metabolic risk factors. Recent research highlights the gut microbiome's role in metabolic regulation, suggesting that modulation through probiotics, prebiotics, and synbiotics may provide a novel approach to managing MetS. This umbrella review aims to integrate insights from existing meta-analyses to explore how changes in gut microbiota influence key body measurement indicators in individuals with MetS.

A systematic search of PubMed, Scopus, and Web of Science databases identified meta-analyses that assessed the impact of probiotics, prebiotics, or synbiotics on anthropometric indices in MetS patients.

The results indicated that microbial therapy leads to a significant reduction in body mass index (BMI) (SMD: -0.22; 95% CI: -0.35 to -0.09; P < 0.01) and waist circumference (WC) (SMD: -0.47; 95% CI: -0.80 to -0.15; P < 0.01). However, microbial therapy did not significantly affect body fat mass (SMD: -0.30; 95% CI: -0.64 to 0.02; P = 0.06), body fat percentage (SMD: -0.29; 95% CI: -0.62 to 0.03; P = 0.07), waist-to-hip ratio (SMD: -0.09; 95% CI: -0.46 to 0.28; P = 0.63), and weight (SMD: -0.06; 95% CI: -0.21 to 0.08; P = 0.37).

Gut microbial modulation, mainly through probiotics and synbiotics, shows promise in reducing BMI and WC in MetS patients. However, its effects on other anthropometric indices remain uncertain, warranting further high-quality research to fully understand microbial interventions' therapeutic potential.

Resistant starch provides beneficial metabolites through gut microbiota fermentation, and the gut microbiota is modulated by the gut redox status. However, the impact of redox status on high-amylose maize starch (HAMS) fermentation metabolism remains uncertain. Anthocyanins (AC) are dietary antioxidants that modulate the redox status. The effect of antioxidant AC on the fermentation metabolism of HAMS was examined using an in vitro fermentation system. AC lowers the system redox potential. The antioxidant AC and fermentation substrate HAMS (HAMS-AC) synergistically increased gas production and short-chain fatty acids and reduced the pH compared to the individual components. AC promotes HAMS fermentation metabolism to produce butyric acid. HAMS-AC also influences gut microbiota composition and metabolic functions. It facilitated beneficial bacteria proliferation, including Collinsella, Faecalibacterium, Agathobacter, Ruminococcus, and Megasphaera, and suppressed harmful bacteria proliferation, including Desulfovibrio, Barnesiella, Alistipes, Parabacteroides, Dorea, Colidextribacter, and Bilophila. HAMS-AC facilitates amino acid and protein synthesis and metabolism, sugar, nucleotide, energy metabolism, and transport. Overall, the antioxidant AC, by lowering the redox potential of the fermentation system, affects the gut microbiota structure and metabolic function and contributes to HAMS metabolism to produce butyric acid. This provides a novel approach for the modulation of intestinal homeostasis and organismal health.

Coculture systems (CCSs) are experimental tools used to study the interactions of anaerobic bacteria among themselves and the gut epithelial cells under conditions simulating the human gut, unlike those in animal models. Although the studies on animal models are useful in determining the relationship between the causative agents of infections and human infections, they have disadvantages, such as ethical issues, in addition to the differences in the microbiota of the animal and humans. Therefore, the results obtained using animal models cannot be directly extrapolated to humans. CCSs can more completely reflect in vivo gut homeostasis and contribute to better understanding of the interplay between the intestinal cells and anaerobes, prevalent among the gut bacteria. Moreover, they provide new insights on the pathogenesis of infections and aid in assessing the usefulness of new probiotics and antibacterials. Therefore, CCSs, including the gut-on-a-chip models, can significantly improve microbiota-based therapy. Moreover, they can also be used to detect microbiota-derived metabolites such as those with mutagenic properties. The aim of this review was to explore selected CCS models of anaerobes with intestinal epithelium and their application in investigating intestinal homeostasis. The focus was to highlight the application of different CCSs and important data obtained from their implementation.

This review aims to provide an overview of the current and future treatment options for children with food allergies (FAs), highlighting the latest research findings and the potential impact of these new approaches on improving patients' and caregivers' quality of life.

In the last decade, many promising approaches have emerged as an alternative to the standard avoidance of the culprit food with the risk of severe accidental reactions. Desensitization through oral immunotherapy has been introduced in clinical settings as a therapeutic approach, and more recently also omalizumab. In addition, alternative routes of administration for immunotherapy, other biologics, small molecules, probiotics or prebiotics, microbiota transplantation therapy, IGNX001, and PVX108 are being investigated.

The portfolio of available treatment options for food allergies is increasing but several relevant unmet needs remain. This review aims to provide a brief overview of the existing and future treatment options for IgE-mediated food allergies.

Probiotics are pivotal in maintaining or restoring the balance of human intestinal microbiota, a crucial factor in mitigating diseases and preserving the host's health. Exploration into Bacteroides spp. reveals substantial promise in their development as next-generation probiotics due to their profound interaction with host immune cells and capability to regulate the microbiome's metabolism by significantly impacting metabolite production. These beneficial bacteria exhibit potential in ameliorating various health issues such as intestinal disorders, cardiovascular diseases, behavioral disorders, and even cancer. Though it's important to note that a high percentage of them are as well opportunistic pathogens, posing risks under certain conditions. Studies highlight their role in modifying immune responses and improving health conditions by regulating lymphocytes, controlling metabolism, and preventing inflammation and cancer. The safety and efficacy of Bacteroides strains are currently under scrutiny by the European Commission for authorization in food processing, marking a significant step towards their commercialization. The recent advancements in bacterial isolation and sequencing methodologies, coupled with the integration of Metagenome-Assembled Genomes (MAGs) binning from metagenomics data, continue to unveil the potential of Bacteroides spp., aiding in the broader understanding and application of these novel probiotics in health and disease management.

With the rapidly aging human population, age-related cognitive decline and dementia are becoming increasingly prevalent worldwide. Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota, microbial metabolites, and the functions of astrocytes. The microbiota-gut-brain axis has been the focus of multiple studies and is closely associated with cognitive function. This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases. This article also summarizes the gut microbiota components that affect astrocyte function, mainly through the vagus nerve, immune responses, circadian rhythms, and microbial metabolites. Finally, this article summarizes the mechanism by which the gut microbiota-astrocyte axis plays a role in Alzheimer's and Parkinson's diseases. Our findings have revealed the critical role of the microbiota-astrocyte axis in age-related cognitive decline, aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

Kidney transplant recipients are prescribed an immunosuppressive therapy (IST) and some of them follow a high fat diet (HFD) despite medical recommendations. Both are frequently associated with gut microbiota changes and metabolic disorders. We aimed at precisely identifying the effect of the IST and the HFD on metabolic parameters and the gut microbiota in mice, and at establishing correlations between the latters.

8-week-old male mice were treated with IST (a combination of prednisone, mycophenolate mofetil and tacrolimus) or not and were fed HFD or standard chow. Metabolic parameters were measured, and the gut microbiota was explored by the quantification of specific bacterial groups by qPCR and by 16S rDNA sequencing.

The HFD increased insulinemia and decreased the fecal proportion of Bacteroidetes and of Bacteroides. The IST increased systolic blood pressure and the fecal proportion of Escherichia coli. The HFD and the IST administered together resulted in an additive effect on glucose intolerance, high fasting blood glucose, homeostasis model assessment of insulin resistance (HOMA-IR), percentage of fat mass, blood triglyceride, blood cholesterol, and endotoxemia. On the opposite, the HFD and the IST had antagonistic effects on body weight, the proportion of Firmicutes, the Firmicutes/Bacteroidetes ratio, and the proportion of Clostridium leptum, Bifidobacterium, and Lactobacillus in the feces. Finally, we found that the correlations between gut bacterial communities and metabolic consequences of the HFD were altered by the IST.

The IST and the HFD have specific consequences on the gut microbiota and metabolism. We hypothesize that the metabolic consequences are at least partially mediated by IST/HFD-induced dysbiosis.