Biology subjects

Steimle, A.

Publications and source records attributed to Steimle, A..

3 recordsLinked to original sources

bioRxiv2023

Gut microbiome-based prediction of autoimmune neuroinflammation

Gut commensals are linked to neurodegenerative diseases, yet little is known about causal and functional roles of microbial risk factors in the gut-brain axis. Here, we employed a pre-clinical model of multiple sclerosis in mice harboring distinct complex microbiotas and six defined strain combinations of a functionally-characterized synthetic human microbiota. Discrete microbiota compositions resulted in different probabilities for development of severe autoimmune neuroinflammation. Nevertheless, assessing presence or the relative abundances of a suspected microbial risk factor failed to predict disease courses across different microbiota compositions. Importantly, we found considerable inter-individual disease course variations between mice harboring the same microbiota. Evaluation of multiple microbiome-associated functional characteristics and host immune responses demonstrated that the immunoglobulin A-coating index of Bacteroides ovatus before disease onset is a robust individual predictor for disease development. Our study highlights that the "microbial risk factor" concept needs to be seen in the context of a given microbial community network, and host-specific responses to that community must be considered when aiming for predicting disease risk based on microbiota characteristics.

microbiology↗

bioRxiv2021

Deprivation of dietary fiber in specific-pathogen-free mice promotes susceptibility to the intestinal mucosal pathogen Citrobacter rodentium

The change of dietary habits in Western societies, including reduced consumption of fiber, is linked to alterations in gut microbial ecology. Nevertheless, mechanistic connections between diet-induced microbiota changes that affect colonization resistance and enteric pathogen susceptibility are still emerging. We sought to investigate how a diet devoid of soluble plant fibers impacts the structure and function of a conventional gut microbiota in specific-pathogen-free (SPF) mice and how such changes alter susceptibility to a rodent enteric pathogen. We show that absence of dietary fiber intake leads to shifts in the abundances of specific taxa, microbiome-mediated erosion of the colonic mucus barrier, a reduction of intestinal barrier-promoting short-chain fatty acids, and increases in markers of mucosal barrier integrity disruption. Importantly, our results highlight that these low fiber diet-induced changes in the gut microbial ecology collectively contribute to a lethal colitis by the mucosal pathogen Citrobacter rodentium, which is used as a mouse model for enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively). Our study indicates that modern, low-fiber Western diets might make individuals more prone to infection by enteric pathogens via the disruption of mucosal barrier integrity by diet-driven changes in the gut microbiota, illustrating possible implications for EPEC and EHEC infections.

microbiology↗

bioRxiv2021

Dietary modulation alters susceptibility to Listeria monocytogenes and Salmonella typhimurium in a gut microbiota-independent manner

Food safety has considerably improved worldwide, yet infections with food-borne human enteric pathogens, such as Listeria spp. and Salmonella spp., still cause numerous hospitalizations and fatalities. Thus, the need to shed more light on the mechanisms of enteropathogenesis is apparent. Since dietary alterations, including fiber deficiency, might impact the colonization resistance by the gut microbiota, studying diet-microbiota-pathogen axis holds promise in further understanding the pathogenesis mechanisms. Using a gnotobiotic mouse model containing a 14-member synthetic human gut microbiota (14SM), we have previously shown that dietary fiber deprivation promotes proliferation of mucin-degrading bacteria leading to a microbiota-mediated erosion of the colonic mucus barrier, which results in an increased susceptibility towards the rodent enteric pathogen Citrobacter rodentium. Here, we sought to understand how low-fiber diet affects susceptibility to Listeria monocytogenes and Salmonella typhimurium infections in our 14SM gnotobiotic mouse model, in BALB/c and C57BL/6N backgrounds, respectively. Intriguingly and in contrast to our results with C. rodentium, we observe that depriving mice of dietary fiber protected them from infections with the pathogens compared to mice fed a standard chow. The microbiota delayed the overall pathogenicity as compared to the onset of disease observed in germ-free control mice; nevertheless, we observe the same effect of diet in germ-free mice, suggesting that the susceptibility is microbiota independent. Our study points out an important observation that dietary fiber plays a crucial role on either the host susceptibility, the virulence of these pathogens, or both, which would be judicious to design and interpret future studies. ImportanceHuman enteric pathogens Listeria monocytogenes and Salmonella typhimurium are employed as classical models in rodent hosts to understand the pathogenesis mechanisms of food-borne pathogens. Research in the past decade has stressed importance of the composition of the gut microbiota in modulating susceptibility to these pathogens. Our results--using gnotobiotic mice and germ-free control animals--additionally suggest that the dietary fiber components dominate the impact of enteropathogenic virulence over the pathogenicity-modulating properties of the gut microbiota. The significance of our research is in the need to carefully choose a certain chow when performing the enteropathogen-associated mouse experiments and to cautiously match the rodent diets when trying to replicate experiments across different laboratories. Finally, our data underscore the importance of germ-free control animals to study these pathogens, as our findings would have been prone to misinterpretation in the absence of these controls.

microbiology↗