Gut microbiota in rheumatoid arthritis: Mechanistic insights, clinical biomarkers, and translational perspectives.

Using the microbiome in clinical practice.

BackgroundGut microbiota alterations are important in irritable bowel syndrome (IBS). The aim was to investigate the effect of fecal microbiota transplantation (FMT) on gut microbiota and the symptoms in patients with IBS.Material and methodsThe study included 13 IBS patients according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered to the descending part of the duodenum via a gastroscope. Feces were collected from donors and patients before FMT, and from the patients at 1, 3 and 12 weeks and donors and patients at 20/28 weeks after FMT. Microbiota analysis was performed using GA-map Dysbiosis test (Genetic Analysis AS, Oslo, Norway). The patients completed the following questionnaires before and at the aforementioned weeks after FMT: IBS Symptom Questionnaire (IBS-SQ), IBS-Symptom Severity Scoring system (IBS-SSS), Short Form of Nepean Dyspepsia Index (SF-NDI), Bristol stool form scale, the Eysenck Personality Questionnaire-Neuroticism and Hospital Anxiety and Depression.ResultsDonors and IBS patients had significantly different bacterial strain signals before FMT (Ruminococcus gnavus, Actinobacteria and Bifidobacteria) that became non-significant after 3 weeks following FMT. The changes in gut microbiota were similar between donors and patients at 20/28 weeks after FMT. Thus, patients’ microbiota profiles became more-or-less similar to donors.The scores of all the questionnaires were significantly improved at all time points following FMT. No reported adverse effects.ConclusionsFMT was associated with a change in gut microbiota and improvement in IBS symptoms and quality of life lasting for up to 28 weeks.Trial registrationClinicalTrials.gov ID: NCT03333291

Fecal Microbiota Transplantation for Ulcerative Colitis: Not Just Yet

HDAC/NF-κB signaling pathway mediates gut microbiota dysbiosis in rheumatoid arthritis: Intervention mechanisms of Fengshining decoction.

Clear roles and mechanisms in explaining gut microbial dysbiosis and microbial metabolites short-chain fatty acids (SCFAs) alterations in chronic cerebral ischemic pathogenesis have yet to be explored. In this study, we investigated chronic cerebral hypoperfusion (CCH)-induced gut microbiota and metabolic profiles of SCFAs as well as the effects and mechanisms of fecal microbiota transplantation (FMT) and SCFAs treatment on CCH-induced hippocampal neuronal injury. Bilateral common carotid artery occlusion (BCCAo) was used to establish the CCH model. Gut microbiota and SCFAs profiles in feces and hippocampus were evaluated by 16S ribosomal RNA sequencing and gas chromatography-mass spectrometry. RNA sequencing analysis was performed in hippocampal tissues. The potential molecular pathways and differential genes were verified through western blot, immunoprecipitation, immunofluorescence, and ELISA. Cognitive function was assessed via the Morris water maze test. Ultrastructures of mitochondria and synapses were tested through a transmission electron microscope. Chronic cerebral hypoperfusion induced decreased fecal acetic and propionic acid and reduced hippocampal acetic acid, which were reversed after FMT and SCFAs administration by changing fecal microbial community structure and compositions. Furthermore, in the hippocampus, FMT and SCFAs replenishment exerted anti-neuroinflammatory effects through inhibiting microglial and astrocytic activation as well as switching microglial phenotype from M1 toward M2. Moreover, FMT and SCFAs treatment alleviated neuronal loss and microglia-mediated synaptic loss and maintained the normal process of synaptic vesicle fusion and release, resulting in the improvement of synaptic plasticity. In addition, FMT and SCFAs supplement prevented oxidative phosphorylation dysfunction via mitochondrial metabolic reprogramming. The above effects of FMT and SCFAs treatment led to the inhibition of CCH-induced cognitive impairment. Our findings highlight FMT and SCFAs replenishment would be the feasible gut microbiota-based strategy to mitigate chronic cerebral ischemia-induced neuronal injury.

Therapeutic potential of probiotics in gut microbial homeostasis and Rheumatoid arthritis

A chronic autoimmune illness that causes joint destruction and inflammation, rheumatoid arthritis (RA) often results in disability. Genetic, environmental, and immune system variables all have a role in the pathophysiology of RA. The complex community of bacteria that live in the gastrointestinal system, known as the gut microbiota, has been implicated in the onset and progression of RA in recent years, according to mounting data. An imbalance in the gut microbiota's composition, known as dysbiosis, has been noted in RA patients. This imbalance may impact inflammatory pathways and immunological responses, which in turn may contribute to the development and severity of the illness. Research has shown that some bacterial species, including Firmicutes, Bacteroidetes, and Proteobacteria, are either more abundant or less prevalent in RA patients than in healthy people. The gut-immune system axis may be modulated, immunological tolerance may be affected, and pro-inflammatory cytokine production may be enhanced by these microbial changes, all of which may lead to systemic inflammation linked to RA. Moreover, changes in intestinal permeability and a rise in microbial metabolite translocation may make autoimmune reactions worse. Probiotics, antibiotics, and dietary changes have also been investigated as possible treatment approaches to help RA patients regain the balance of their gut microbiota. Still up for debate, however, are the precise ways in which the gut microbiome affects RA. Comprehending the complex connection between gut microbiota and RA may give new perspectives on managing and preventing the condition, as well as future prospects for medicines that target the microbiome.

The human genome codes for approximately 23,000 genes,1 yet some experts have suggested that the total information coded by the human genome alone is not enough to carry out all of the body’s biological functions.2 A growing number of studies suggest that part of what determines how the human body functions may be not only our own genes, but also the genes of the trillions of microorganisms that reside on and in our bodies. The genomes of the bacteria and viruses of the human gut alone are thought to encode 3.3 million genes.3 “The genetic richness and complexity of the bugs we carry is much richer than our own,” says Jayne Danska, an immunologist at the Hospital for Sick Children Research Institute in Ontario, Canada. “They serve as a buffer and interpreter of our environment. We are chimeric organisms.” Figure 1 False-color scanning electron micrograph shows the surface of the colon mucosa with pink clusters of rod-shaped bacteria, possibly Escherichia coli, attached. The genomes of the bacteria and viruses of the human gut alone are thought to encode 3.3 million ... A role for gut microbes in gastrointestinal function has been well documented since researchers first described differences in the fecal bacteria of people with inflammatory bowel disease.4 The molecular mechanisms responsible for the gut microbiome’s impact on metabolism and diseases throughout the body remain largely unknown. However, researchers are beginning to decipher how the microorganisms of the human intestinal tract influence biological functions beyond the gut and play a role in immunological, metabolic, and neurological diseases.

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.

The gut microbiome has a crucial role in host metabolism and immune regulation, and there is growing evidence that dysbiosis may be associated with the pathogenesis of cardiovascular disease (CVD). This narrative review provides an overview of the recent literature on mechanistic connections between the gut and heart, as well as on the therapeutic strategies and research gaps in the gut-heart axis. We conducted a systematic literature search on PubMed and Embase databases with MeSH and keyword terms: 'gut microbiome', 'cardiovascular disease', 'TMAO', 'short-chain fatty acids', 'probiotics' and 'faecal microbiota transplantation'. We considered human and relevant animal studies focusing on mechanistic pathways or microbiome treatments and excluded editorials, small (less than 10 subjects) case series and articles not published in the English language. Key microbiota-derived metabolites, trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), contribute to atherogenesis, blood pressure and myocardial inflammation. Dysbiosis-induced barrier dysfunction and disturbed bile acid signalling also serve as the mediators of cardiac remodelling. Dietary fibre, probiotics/prebiotics, postbiotics and faecal microbiota transplantation are emerging interventions for the modulation of CVD risk. Nevertheless, most result from observational studies, whilst such are heterogeneous in sequencing platforms and too small to draw any definitive conclusions. The modulation of gut microbiome might be a new target for CVD prevention and treatment. Large-scale, standardized randomized trials with hard cardiovascular endpoints, as well as integrated multi-omics profiling, will be required to validate microbial biomarkers and to optimize microbiome-based interventions.

Background:Rheumatoid arthritis (RA) is associated with a high risk of cardiovascular (CV) risks, including accelerated atherosclerosis, left ventricular hypertrophy and decreased heart rate variability (HRV). HRV decrease reflects the inability...

Aims: To assess the long-term efficacy and safety of single-donor, low-intensity fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), and to identify the outcome-specific gut bacteria.Design: Thirty-one patients with active UC (Mayo scores ≥ 3) were recruited, and all received FMT twice, at the start of the study and 2∼3 months later, respectively, with a single donor and a long-term follow-up. The fecal microbiome profile was accessed via 16S rRNA sequencing before and after FMT.Results: After the first FMT, 22.58% (7/31) of patients achieved clinical remission and endoscopy remission, with the clinical response rate of 67.74% (21/31), which increased to 55% (11/20) and 80% (16/20), respectively, after the second FMT. No serious adverse events occurred in all patients. During 4 years of follow-up, the mean remission period of patients was 26.5 ± 19.98 m; the relapse rate in the 12 remission patients was 33.33% within 1 year, and 58.3% within 4 years. At baseline, UC patients showed an enrichment in some proinflammatory microorganisms compared to the donor, such as Bacteroides fragilis, Clostridium difficile, and Ruminococcus gnavus, and showed reduced amounts of short-chain fatty acid (SCFA) producing bacteria especially Faecalibacterium prausnitzii. FMT induced taxonomic compositional changes in the recipient gut microbiota, resulting in a donor-like state. Given this specific donor, UC recipients with different outcomes showed distinct gut microbial features before and after FMT. In prior to FMT, relapse was characterized by higher abundances of Bacteroides fragilis and Lachnospiraceae incertae sedis, together with lower abundances of Bacteroides massiliensis, Roseburia, and Ruminococcus; Prevotella copri was more abundant in the non-responders (NR); and the patients with sustained remission (SR) had a higher abundance of Bifidobacterium breve. After FMT, the NR patients had a lower level of Bifidobacterium compared to those with relapse (Rel) and SR, while a higher level of Bacteroides spp. was observed in the Rel group.Conclusion: Low-intensity single donor FMT could induce long remission in active UC. The gut microbiota composition in UC patients at baseline may be predictive of therapeutic response to FMT.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder whose precise etiology remains unclear, though growing evidence implicates gut microbiota in its pathogenesis. This study aimed to investigate the role of gut microbiota in the onset and progression of RA by employing fecal microbiota transplantation (FMT) in a collagen-induced arthritis (CIA) mouse model using DBA/1J and Aire-/- strains. Mice received FMT from healthy donors, treatment-naïve RA patients, or treated RA patients in relapse, followed by assessment of microbiota composition via 16S rRNA sequencing, arthritis severity scoring, histological evaluations, and systemic inflammatory markers. The findings revealed distinct microbiota clustering patterns post-FMT across experimental groups, highlighting strain-specific colonization effects. Notably, genera such as Bifidobacterium and Paraprevotella correlated positively with arthritis severity in DBA/1J mice, whereas Corynebacterium, Enterorhabdus, and Odoribacter exhibited negative correlations, suggesting potential protective roles. Despite these microbial differences, minor variations in arthritis scores, paw inflammation, or systemic inflammation were observed among FMT groups. This indicates that although gut microbiota alterations are associated with RA pathogenesis, further investigation with larger cohorts and comprehensive sequencing approaches is essential to elucidate the therapeutic potential of microbiome modulation in autoimmune diseases.

BackgroundLymph node metastasis (LNM) is a prognostic factor in pancreatic cancer. The association between the gut microbiota and LNM remains unexplored. This study aimed to characterize the gut microbiota and metabolomic profiles associated with LNM and to investigate their potential as predictive biomarkers.MethodsFecal samples from pancreatic cancer patients undergoing surgery were analyzed using metagenomic sequencing and untargeted metabolomics. The patients were categorized into LNM and non-LNM (NLNM) groups. Differential microbiome taxa were analyzed using the DESeq2 package. Random forest predictive models were developed based on metagenomic and metabolomic data, with performance assessed using leave-one-out cross-validation (LOOCV).ResultsA total of 26 patients with LNM and 29 patients without LNM were included. Principal coordinates analysis (PCoA) revealed significant differences in microbiota composition between the two groups (Anosim, p = 0.047). The absolute counts of Ruminococcus gnavus and Blautia wexlera were significantly decreased in LNM. Tryptophan-derived metabolites, indole-3-lactic acid (3-ILA) and indole-3-acrylic acid (3-IA), were downregulated in LNM. Functional pathway analysis showed downregulation of tryptophan metabolism in LNM, while cancer-related pathways were upregulated. Correlation analysis revealed a significant positive association between Ruminococcus gnavus and 3-ILA/3-IA levels. Moreover, Ruminococcus gnavus was positively correlated with CD8+ T cells. Predictive models based on the gut microbiota and metabolites distinguished LNM from NLNM, with AUC values of 0.854 and 0.940, respectively.ConclusionThe gut microbiota and metabolites exhibit significant alterations during lymph node metastasis in pancreatic cancer, especially Ruminococcus gnavus, Blautia wexlera, and tryptophan metabolites (3-ILA and 3-IA). Gut microbial and metabolite signatures may serve as potential non-invasive biomarkers for predicting LNM in pancreatic cancer. Further functional validation is required to determine whether and how the gut microbiota and metabolites may mediate lymph node metastasis.

Multi-kingdom gut microbiota dysbiosis is associated with the development of pulmonary arterial hypertension.