The Microbiota-Human Health Axis.

The gut microbiome is a heterogeneous population of microbes comprising viruses, bacteria, fungi, and protozoa. Such a microbiome is essential for sustaining host equilibrium, and its impact on human health can be altered by a variety of factors such as external variables, social behavior, age, nutrition, and genetics. Gut microbes’ imbalances are related to a variety of chronic diseases including cancer, obesity, and digestive disorders. Globally, recent findings show that intestinal microbes have a significant role in the formation of cardiovascular disease (CVD), which is still the primary cause of fatalities. Atherosclerosis, hypertension, diabetes, inflammation, and some inherited variables are all cardiovascular risk variables. However, studies found correlations between metabolism, intestinal flora, and dietary intake. Variations in the diversity of gut microbes and changes in their activity are thought to influence CVD etiology. Furthermore, the gut microbiota acts as an endocrine organ, producing bioactive metabolites such as TMA (trimethylamine)/TMAO (trimethylamine N-oxide), SCFA (short-chain fatty acids), and bile acids, which have a substantial impact on host wellness and disease by multiple mechanisms. The purpose of this overview is to compile current evidence highlighting the intricate links between gut microbiota, metabolites, and the development of CVD. It focuses on how intestinal dysbiosis promotes CVD risk factors such as heart failure, hypertension, and atherosclerosis. This review explores the normal physiology of intestinal microbes and potential techniques for targeting gut bacteria for CVD treatment using various microbial metabolites. It also examines the significance of gut bacteria in disease treatment, including supplements, prebiotics, probiotics, antibiotic therapies, and fecal transplantation, which is an innovative approach to the management of CVD. As a result, gut bacteria and metabolic pathways become increasingly attractive as potential targets for CVD intervention.

The Western diet (WD) is characterized by high fat, high sugar, high salt and low fiber. WD can disrupt the homeostasis of the intestinal flora and become an important factor in the occurrence and development of Cardiovascular Diseases (CVD). This review elucidates the core mechanism through which WD-induced intestinal flora dysbiosis contributes to the development of CVD. Specifically, the disruption of intestinal barrier function promotes the generation of pathogenic metabolites, such as trimethylamine-N-oxide (TMAO), while simultaneously suppressing the production of beneficial metabolites, including short-chain fatty acids (SCFAs). This metabolic shift subsequently triggers systemic inflammatory responses, oxidative stress, and metabolic disturbances, thereby accelerating the progression of CVD-related conditions, such as atherosclerosis and hypertension. Meanwhile, this review systematically summarizes key intervention strategies targeting the gut microbiota. Accumulating evidence indicates that interventions such as probiotics, prebiotics, the Mediterranean diet, and fecal microbiota transplantation (FMT) can effectively restore intestinal microbial homeostasis, enhance the production of SCFAs, and mitigate the risk of CVD. Notably, long-term dietary patterns have demonstrated significant efficacy in reshaping the gut ecosystem, underscoring the importance of sustainable lifestyle modifications. Therefore, this study aims to integrate current knowledge regarding the underlying molecular mechanisms and provide a theoretical basis for developing precise interventions to prevent and treat CVD through modulation of the gut microbiota.

Mode of delivery has an impact on the gut microbiota of newborn infants. It has been reported that infants delivered by Caesarean section (C-section) typically have a lack of Bacteroides species and delayed Bifidobacterium development in the gut microbiota when compared with those delivered vaginally.1 Epidemiologic data have indicated that that C-sections are associated with chronic immune system-related diseases, such as rheumatoid arthritis and type I diabetes.2 It is possible that this association is partly formed in the interaction of the host and the different gut microbiota of infants delivered by C-section.3 Previous attempts to correct the microbiota of infants delivered by C-section have included oral administration of vaginal flora to the newborn infant and probiotic supplements, including Bifidobacteria. However, the impact of these interventions has been limited.4, 5 The gut microbiota of newborn infants who are born vaginally are colonised by maternal gut bacteria. That is why we studied whether a faecal transplant from mothers to newborn infants delivered by C-section would correct the imbalance caused by this mode of delivery.6, 7 We carried out a proof of principle and safety trial and recruited 17 pregnant women aged 31–40 who were scheduled for an elective C-section. After careful screening for potential pathogens, seven of these expectant mothers were selected for a faecal transplant once their infants were born. A faecal sample was obtained two weeks before their planned C-section and prepared for transplantation. The infants, five girls and two boys, received a small amount of faecal transplant from their mothers, namely 3.5–7 mg, which was mixed with their mother's milk when they were first fed within two hours of delivery.7 The infants, who were all born at 37 weeks ± 3 days and weighed 2861–3528 grams, were followed up for three months, and there were no clinical symptoms association with the transplantation. Repeated faecal sampling from the infants that we treated showed that the composition of their faecal microbiota was strikingly similar to the faecal microbiota samples previously collected from vaginally delivered infants. In particular, the lack of Bacteroides species and Bifidobacterium that are typically observed in infants delivered by C-section were corrected. Moreover, the microbiome of both the vaginally born infants, and those born by C-section and given faecal transplants, showed mark differences to infants who were previously given maternal vaginal flora.7 Our study demonstrates that the intestinal microbiota of infants delivered by C-section can be successfully normalised by maternal faecal microbiota transplants. However, the prerequisites for this method are meticulous screening of the mother and careful follow-up of the newborn infant. To assess the long-term effects of faecal transplants on the intestinal flora, and the growth and development of newborn infants, we are currently performing a larger randomised controlled trial on infants delivered by C-section. The trial will also enable us to study the interactions between the intestinal microbiome and the early development of the immune system, which may generate new data on the origins of atopic and autoimmune diseases. Future studies are required to show whether providing infants born by C-section with faecal transplants could become part of clinical routines. At the moment, it is important that faecal transplants should only be performed as part of research projects and that they should include rigorous clinical and microbiological screening and follow-ups. The authors have no conflicts of interest to declare.

Cardiovascular disease (CVD) has been classified as one of the leading causes of morbidity and mortality worldwide. CVD risk factors include smoking, hypertension, dyslipidaemia, obesity, inflammation and diabetes. The gut microbiota can influence human health through multiple interactions and community changes are associated with the development and progression of numerous disease states, including CVD. The gut microbiota are involved in the production of several metabolites, such as short-chain fatty acids (SCFAs), bile acids and trimethylamine-N-oxide (TMAO). These products of microbial metabolism are important modulatory factors and have been associated with an increased risk of CVD. Due to its association with CVD development, the gut microbiota has emerged as a target for therapeutic approaches. In this review, we summarise the current knowledge on the role of the gut microbiome in CVD development, and associated microbial communities, functions, and metabolic profiles. We also discuss CVD therapeutic interventions that target the gut microbiota such as probiotics and faecal microbiota transplantation.

The change in the gut microbiome and microbial metabolites in a patient suffering from severe and enduring anorexia nervosa (AN) and diagnosed with small intestinal bacterial overgrowth syndrome (SIBO) was investigated. Microbial gut dysbiosis is associated with both AN and SIBO, and therefore gut microbiome changes by serial fecal microbiota transplantation (FMT) is a possible therapeutic modality. This study assessed the effects of FMT on gut barrier function, microbiota composition, and the levels of bacterial metabolic products. The patient treatment with FMT led to the improvement of gut barrier function, which was altered prior to FMT. Very low bacterial alpha diversity, a lack of beneficial bacteria, together with a great abundance of fungal species were observed in the patient stool sample before FMT. After FMT, both bacterial species richness and gut microbiome evenness increased in the patient, while the fungal alpha diversity decreased. The total short-chain fatty acids (SCFAs) levels (molecules presenting an important source of energy for epithelial gut cells) gradually increased after FMT. Contrarily, one of the most abundant intestinal neurotransmitters, serotonin, tended to decrease throughout the observation period. Overall, gut microbial dysbiosis improvement after FMT was considered. However, there were no signs of patient clinical improvement. The need for an in-depth analysis of the donor´s stool and correct selection pre-FMT is evident.

Bacterial viability in faecal transplants: Which bacteria survive?

In recent years, DNA sequencing and mass spectrometry technologies have advanced greatly, enabling the collection of more information on the gut microbiome and its metabolome in order to assess the influence of the gut microbiota on human health at a whole-system level. As the gut microbiota has been likened to a functional and measurable organ consisting of prokaryotic cells, which creates the unique gut ecosystem together with the host eukaryotic cells, metagenome and metabolome technologies have demonstrated that the gut microbiota contributes to host overall health status to a great extent. In this chapter, the detailed relationships between gut microbiota and its metabolites like choline, phenols, bile acids and short-chain fatty acids in host health and etiopathogenesis of various metabolic diseases such as obesity, diabetes, atherosclerosis, non-alcoholic fatty liver disease and extraintestinal diseases like multiple sclerosis, chronic kidney disease and autism will be discussed. In addition, therapeutic interventions like probiotic and prebiotic administrations and faecal microbiota transplantations which are recently used in dysbiosis restoration will be reviewed. This unique biology-wide approach of integrating metagenome and metabolome information would aid in the better understanding of the intricate interplay between gut microbiota and host metabolism. We believe that this novel integration of the microbiome, metatranscriptome and metabolome information will lay the way towards an improved holistic understanding of the complex mammalian superorganism. This modelling of the metabolic interactions between lifestyle, dietary habits and the gut microbiota, otherwise known as the “integrated omics-based understanding of the gut ecosystem”, will culminate in the comprehensive interpretation of the role and impact of microbial health potentials, thereby providing exciting novel therapeutic approaches for optimal host health.

Canine acute hemorrhagic diarrhea syndrome (AHDS) has been associated in some studies with Clostridioides perfringens overgrowth and toxin-mediated necrosis of the intestinal mucosa. We aimed to determine the effect of a single fecal microbiota transplantation (FMT) on clinical scores and fecal microbiomes of 1 and 7 dogs with AHDS from New Zealand and South Africa. We hypothesized that FMT would improve AHDS clinical scores and increase microbiota alpha-diversity and short-chain fatty acid (SCFA)-producing microbial communities’ abundances in dogs with AHDS after FMT. We sequenced the V3-V4 region of the 16S-rRNA gene in the feces of AHDS FMT-recipients and sham-treated control dogs, and their healthy donors at admission, discharge, and 30 days post-discharge. There were no significant differences in median AHDS clinical scores between FMT-recipients and sham-treated controls at admission or discharge (P = 0.22, P = 0.41). At admission, the Shannon diversity index (SDI) was lower in AHDS dogs than healthy donors (P = 0.002). The SDI did not change from admission to 30 days in sham-treated dogs yet increased in FMT-recipients from admission to discharge (P = 0.04) to levels not different than donors (P = 0.33) but significantly higher than sham-treated controls (P = 0.002). At 30 days, the SDI did not differ between FMT recipients, sham-treated controls, and donors (P = 0.88). Principal coordinate analysis of the Bray-Curtis index separated post-FMT and donor dogs from pre-FMT and sham-treated dogs (P = 0.009) because of increased SCFA-producing genera’s abundances after FMT. A single co-abundance subnetwork contained many of the same OTUs found to be differentially abundant in FMT-recipients, and the abundance of this module was increased in FMT-recipients at discharge and 30 days, compared to sham-treated controls. We conclude in this small pilot study FMT did not have any clinical benefit. A single FMT procedure has the potential to increase bacterial communities of SCFA-producing genera important for intestinal health up to 30 days post-FMT.

BackgroundThe mitochondrial amidoxime-reducing component-2 (Mtarc) enzyme complex is located on the outer mitochondrial membrane and may be involved in lipid metabolism regulation.AimThis study evaluated the impact of fecal microbiota transplantation (FMT) on phenotypic outcomes, liver accumulation of fatty acids (FAs), and modifications to the gut microbial community, as well as the abundance of short-chain fatty acids (SCFAs) and amino acids (AAs), in both sexes of Mtarc2 knockout (Mtarc2-KO) and C57BL/6 N mice fed a Western Diet (WD).MethodologyMice were fed a WD (study groups) or normal diet (control groups) and were subjected to intestinal flushing with either a polyethylene glycol (PEG) solution (study groups) or water (control groups); this was followed by intragastrical administration of a human feces suspension (study groups) or water (control groups). Liver FA composition and fecal SCFAs and AAs were measured by mass spectrometry. Metagenomic-based analysis was performed by sequencing the variable V3 and V4 regions of the bacterial 16 S rRNA gene.Principal findingsWeight gain in C57BL/6 N mice fed a WD was significantly higher than in Mtarc2-KO mice. Compared with water only, intestinal cleansing with PEG resulted in significantly lower weight gain in C57BL/6 N mice but not in Mtarc2-KO mice. FMT did not affect body weight in C57BL/6 N mice, and decreased in Mtarc2-KO females and males fed a ND and a WD, respectively. No significant differences in liver FAs composition were found between mouse strains. While PEG treatment significantly affected liver FAs composition, FMT modulated FAs levels to a much smaller extent. However, neither intestinal cleansing nor FMT affected the microscopic findings of fatty liver. WD feeding affected bacterial diversity, taxonomy and SCFAs and AAs abundances in Mtarc2-KO and C57BL/6 N mice not subjected to PEG treatment. Both intestinal cleansing alone and FMT modulated gut bacterial composition, especially in C57BL/6 N mice, and metabolite abundances in Mtarc2-KO mice.ConclusionWD and FMT differentially modified phenotypic parameters, liver FA composition, and gut bacteria in comparisons between Mtarc2-KO and C57BL/6 N. This suggests the Mtarc complex plays a significant role in regulating energy metabolism in mice.

The role of gut microbiota in the pathogenesis of cardiovascular diseases (CVD) and metabolic syndrome has attracted massive attention in the past decade. Accumulating evidence has revealed that the metabolic potential of gut microbiota can be identified as a contributing factor in the development of atherosclerosis, hypertension, heart failure, obesity, diabetes mellitus. The gut-host interaction occurs through many pathways including trimethylamine-N-oxide pathway (TMAO), short-chain fatty acids and second bile acids pathways. TMAO (the hepatic oxidation product of the microbial metabolite of trimethylamine) enhances platelet hyperreactivity and thrombosis risk and predicts major adverse cardiovascular events. Short-chain fatty acids and second bile acids, which are produced with the help of microbiota, can modulate host lipid metabolism as well as carbohydrate metabolism through several receptors such as G-protein-coupled receptors 41,43, farnesoid X-receptor, Takeda-G-protein-receptor-5. This way microbiota can impact host lipid levels, processes of weight gain, insulin sensitivity. Besides these metabolism-dependent pathways, there are some other pathways, which link microbiota and the pathogenesis of CVD. For example, lipopolysaccharide, the major component of the outer bacterial membrane, causes metabolic endotoxemia and low-grade systemic inflammation and contribute this way to obesity and progression of heart failure and atherosclerosis. This review aims to illustrate the complex interplay between microbiota, their metabolites, and the development and progression of CVD and metabolic syndrome. It is also discussed how modulating of gut microbiota composition and function through diet, prebiotics, probiotics and fecal microbiota transplantation can become a novel therapeutic and preventative target for CVD and metabolic syndrome. Many questions remain unresolved in this field and undoubtedly further studies are needed.

BackgroundDysbiosis of the intestinal microbiota plays a crucial role in the initiation and development of graft-versus-host disease (GVHD). Fecal microbiota transplantation (FMT) has been reported to be effective for refractory acute GVHD; however, whether FMT is effective for refractory chronic GVHD (cGVHD) remains unknown.MethodsTo investigate the efficacy and safety of FMT for refractory cGVHD and the underlying mechanism, 12 patients with refractory cGVHD received FMT via colonoscopy, and the response was evaluated at 12 weeks after FMT.ResultsAmong the 12 patients who underwent FMT, 1 patient achieved a complete response, and 5 patients achieved a partial response. Patients with refractory cGVHD presented lower α diversity and higher abundance of Escherichia-Shigella andEnterobacteriaceae. FMT increased gut microbial diversity, increased the abundance of short-chain fatty acid (SCFA)-producing bacteria, and decreased the abundance of Escherichia-Shigella and Enterobacteriaceae in responder patients. Moreover, it increased SCFA levels in fecal samples from the responder group and promoted the expansion of peripheral CD4+CD127- regulatory T (Treg) cells. Colon pathological examination revealed that CD4+ T and CD19+ B cell infiltration decreased and that CD4+ Treg infiltration increased after FMT.ConclusionsThe results of the present study suggest that FMT is feasible and deserves further investigation for use in patients with refractory cGVHD.Trial registrationClinicalTrials.gov (NCT06938165).Supplementary InformationThe online version contains supplementary material available at 10.1186/s12916-025-04336-z.

Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly non-alcoholic fatty liver disease) is a prevalent and progressive condition closely linked to gut microbiota composition. Fecal microbiota transplantation (FMT) may help restore a health-associated microbiome, but its efficacy is often limited by inconsistent engraftment of beneficial taxa. Prebiotics may selectively support keystone microbes associated with reduced MASLD risk. This study evaluated two prebiotics, inulin and xylooligosaccharides (XOS), for their ability to modulate the microbiota of healthy FMT donors in an in vitro gut model, focusing on enriching beneficial taxa and functions associated with MASLD resilience. Stool from eight clinically qualified FMT donors was cultured anaerobically for 24 h with or without prebiotics. Microbiota composition was assessed by 16S rRNA gene sequencing and short-chain fatty acid (SCFA) concentrations were measured using nuclear magnetic resonance. Functional potential was inferred using predictive metagenomic analysis. Prebiotic responses were highly donor-specific, yet both inulin and XOS consistently enriched Bifidobacterium and Bacteroides-genera associated with SCFA production and metabolic health. XOS preferentially enriched Lactobacillus and Parabacteroides, while inulin enhanced Holdemanella and Mediterraneibacter. Functional pathways relevant to MASLD pathophysiology were enriched, including carbohydrate metabolism, vitamin biosynthesis, fatty acid metabolism, and tryptophan degradation. Both prebiotics significantly increased acetate levels, while butyrate showed a donor-dependent increasing trend. These findings suggest that prebiotic supplementation can selectively enrich MASLD-relevant microbial taxa and functions in donor-derived FMT material, supporting their potential as adjuvants to enhance the efficacy and disease-specificity of FMT interventions for MASLD.

The pathogenesis of atopic dermatitis (AD) involves complex factors, including gut microbiota and immune modulation, which remain poorly understood. The aim of this study was to restore gut microbiota via fecal microbiota transplantation (FMT) to ameliorate AD in mice. FMT was performed using stool from donor mice. The gut microbiota was characterized via 16S rRNA sequencing and analyzed using Quantitative Insights into Microbial Ecology 2 with the DADA2 plugin. Gut metabolite levels were determined by measuring fecal short-chain fatty acid (SCFA) contents. AD-induced allergic responses were evaluated by analyzing blood parameters (IgE levels and eosinophil percentage, eosinophil count, basophil percentage, and monocyte percentage), the levels of Th1 and Th2 cytokines, dermatitis score, and the number of mast cells in the ileum and skin tissues. Calprotectin level was measured to assess gut inflammation after FMT. FMT resulted in the restoration of gut microbiota to the donor state and increases in the levels of SCFAs as gut metabolites. In addition, FMT restored the Th1/Th2 balance, modulated Tregs through gut microbiota, and reduced IgE levels and the numbers of mast cells, eosinophils, and basophils. FMT is associated with restoration of gut microbiota and immunologic balance (Th1/Th2) along with suppression of AD-induced allergic responses and is thus a potential new therapy for AD.

Social jetlag, the misalignment between internal circadian rhythms and socially imposed schedules, is increasingly recognized as a risk factor for metabolic disorders such as obesity, type 2 diabetes (T2D), and cardiovascular disease. Recent evidence implicates the gut microbiota as a key mediator in this relationship, operating through a microbiota–gut–metabolic axis that influences host metabolism, immune function, and circadian regulation. Mechanistic studies reveal that social jetlag disrupts microbial rhythmicity, reduces short-chain fatty acid (SCFA) production, impairs intestinal barrier function, and promotes systemic inflammation, which contribute to insulin resistance and metabolic dysfunction. Clinical and preclinical interventions, including time-restricted feeding (TRF)/time-restricted eating (TRE), probiotics or melatonin supplementation, and fecal microbiota transplantation (FMT), demonstrate the potential to restore microbial and metabolic homeostasis by realigning host and microbial rhythms. This review synthesizes mechanistic insights with emerging human and clinical evidence, highlighting the gut microbiota as a novel target for chronotherapeutic strategies aimed at mitigating the metabolic consequences of circadian disruption. Recognizing and treating circadian–microbiome misalignment may provide a clinically actionable pathway to prevent or reverse chronic metabolic diseases in modern populations.

Introduction: Fecal microbiota transplantation (FMT) is a safe and effective therapy for recurrent Clostridium difficile infection (CDI). Although immunocompromised patients are at high risk of CDI, the use of FMT may be limited owing to safety concerns. Since most FMT clinical trials exclude these patients, data on efficacy and safety of FMT in these patients are limited. We report results from a systematicreview and meta-analysis to evaluate the efficacy and safety of FMT in immunocompromised patients. Methods: A systematic search of MEDLINE, Embase and Web of Science was performed up to April 2018, followed by manual search of identified studies. We included case series, case-control or cohort studies, and clinical trials of FMT for CDI in immunocompromised patients with prevention of recurrent CDI as the primary outcome. Our primary analysis focused on calculating weighted pooled cure rate after one or more FMT. Results: A total of 18 studies were included. Among these, 566 immunocompromised patients underwent FMT for recurrent CDI. The various reason for immunosuppression included inflammatory bowel diseases, solid organ transplant (SOT), cancer, human immunodeficiency virus infection, graft versus host disease and hematopoietic stem cell transplants. Of the 566 patients, 430 had clinical cure of CDI with a pooled resolution rate after one FMT of 77.4% (95% CI, 71.6%-83.2%, I2= 57%).The pooled resolution rate increased to 91.5% (95% CI, 87.6%-95.4%, I2=21%) with multiple FMTs. No serious adverse events attributed to FMT were reported in any of the studies. On separating the 9 studies with immunosuppressed IBD patients, resolution after 1 FMT was reported in 328/412 patients, the pooled resolution rate 80.7% (95% CI, 76.6%-84.8%). In three studies with 103 SOT patients, FMT cured 58, with pooled cure rate of 50.2% (95% CI, 29.7%-70.6%). Conclusion: FMT appears to be safe and effective therapy for preventing recurrent CDI in immunocompromised patients. However, efficacy is lower in these patients compared to reported rates in immunocompetent patients. Efficacy improves with multiple FMTs. Although data were not available, repeat non-CDI antibiotic exposure in this population could potentially explain these findings. Studies are needed to explore best treatment practices in these patients including predictors of failed FMT which may identify patients who would benefit from early pre-emptive repeat FMT to prevent recurrent CDI