Next-generation therapeutic bacteria for treatment of obesity, diabetes, and other endocrine diseases

The human gut microbiota has appeared as an important factor affecting host health and intestinal bacteria have recently emerged as potential therapeutics to treat diabetes and other endocrine dis-eases. These mainly anaerobic bacteria have been identified either via comparative "omics" analysis of the intestinal microbiota in healthy and diseased subjects or of data collected by fecal microbiota transplantation studies. Both approaches require advanced and in-depth sequencing technologies to perform massive genomic screening to select bacteria with potential benefits. It has been shown that these potentially therapeutic bacteria can either pro -duce bioactive products that directly influence the host patho-physiology and endocrine systems or produce specific signaling molecules that may do so. These bioactive compounds can be formed via degradation of dietary or host-derived components or the conversion of intermediate compounds produced by fermen-tation of intestinal bacteria. Several of these bacteria have shown causality in preclinical models and entered clinical phase studies, while their mode of action is being analyzed. In this review, we summarize the research on the most promising bacterial candidates with therapeutic properties with a specific focus on diabetes . (c) 2021 Published by Elsevier Ltd.Peer reviewe

Gut microbiota in experimental murine model of Graves’ orbitopathy established in different environments may modulate clinical presentation of disease

Background Variation in induced models of autoimmunity has been attributed to the housing environment and its effect on the gut microbiota. In Graves’ disease (GD), autoantibodies to the thyrotropin receptor (TSHR) cause autoimmune hyperthyroidism. Many GD patients develop Graves’ orbitopathy or ophthalmopathy (GO) characterized by orbital tissue remodeling including adipogenesis. Murine models of GD/GO would help delineate pathogenetic mechanisms, and although several have been reported, most lack reproducibility. A model comprising immunization of female BALBc mice with a TSHR expression plasmid using in vivo electroporation was reproduced in two independent laboratories. Similar orbital disease was induced in both centers, but differences were apparent (e.g., hyperthyroidism in Center 1 but not Center 2). We hypothesized a role for the gut microbiota influencing the outcome and reproducibility of induced GO. Results We combined metataxonomics (16S rRNA gene sequencing) and traditional microbial culture of the intestinal contents from the GO murine model, to analyze the gut microbiota in the two centers. We observed significant differences in alpha and beta diversity and in the taxonomic profiles, e.g., operational taxonomic units (OTUs) from the genus Lactobacillus were more abundant in Center 2, and Bacteroides and Bifidobacterium counts were more abundant in Center 1 where we also observed a negative correlation between the OTUs of the genus Intestinimonas and TSHR autoantibodies. Traditional microbiology largely confirmed the metataxonomics data and indicated significantly higher yeast counts in Center 1 TSHR-immunized mice. We also compared the gut microbiota between immunization groups within Center 2, comprising the TSHR- or βgal control-immunized mice and naïve untreated mice. We observed a shift of the TSHR-immunized mice bacterial communities described by the beta diversity weighted Unifrac. Furthermore, we observed a significant positive correlation between the presence of Firmicutes and orbital-adipogenesis specifically in TSHR-immunized mice. Conclusions The significant differences observed in microbiota composition from BALBc mice undergoing the same immunization protocol in comparable specific-pathogen-free (SPF) units in different centers support a role for the gut microbiota in modulating the induced response. The gut microbiota might also contribute to the heterogeneity of induced response since we report potential disease-associated microbial taxonomies and correlation with ocular disease

Environmental radiation alters the gut microbiome of the bank vole Myodes glareolus

Gut microbiota composition depends on many factors, although the impact of environmental pollution is largely unknown. We used amplicon sequencing of bacterial 16S rRNA genes to quantify whether anthropogenic radionuclides at Chernobyl (Ukraine) impact the gut microbiome of the bank vole Myodes glareolus. Exposure to elevated levels of environmental radionuclides had no detectable effect on the gut community richness but was associated with an almost two-fold increase in the Firmicutes:Bacteroidetes ratio. Animals inhabiting uncontaminated areas had remarkably similar gut communities irrespective of their proximity to the nuclear power plant. Hence, samples could be classified to high-radiation or low-radiation sites based solely on microbial community with >90% accuracy. Radiation-associated bacteria had distinct inferred functional profiles, including pathways involved in degradation, assimilation and transport of carbohydrates, xenobiotics biodegradation, and DNA repair. Our results suggest that exposure to environmental radionuclides significantly alters vertebrate gut microbiota.peerReviewe