A fiber-deprived diet disturbs the fine-scale spatial architecture of the murine colon microbiome.

Compartmentalization of the gut microbiota is thought to be important to system function, but the extent of spatial organization in the gut ecosystem remains poorly understood. Here, we profile the murine colonic microbiota along longitudinal and lateral axes using laser capture microdissection. We found fine-scale spatial structuring of the microbiota marked by gradients in composition and diversity along the length of the colon. Privation of fiber reduces the diversity of the microbiota and disrupts longitudinal and lateral gradients in microbiota composition. Both mucus-adjacent and luminal communities are influenced by the absence of dietary fiber, with the loss of a characteristic distal colon microbiota and a reduction in the mucosa-adjacent community, concomitant with depletion of the mucus layer. These results indicate that diet has not only global but also local effects on the composition of the gut microbiota, which may affect function and resilience differently depending on location.

Lifestyle and Horizontal Gene Transfer-Mediated Evolution of Mucispirillum schaedleri, a Core Member of the Murine Gut Microbiota.

Mucispirillum schaedleri is an abundant inhabitant of the intestinal mucus layer of rodents and other animals and has been suggested to be a pathobiont, a commensal that plays a role in disease. In order to gain insights into its lifestyle, we analyzed the genome and transcriptome of M. schaedleri ASF 457 and performed physiological experiments to test traits predicted by its genome. Although described as a mucus inhabitant, M. schaedleri has limited capacity for degrading host-derived mucosal glycans and other complex polysaccharides. Additionally, M. schaedleri reduces nitrate and expresses systems for scavenging oxygen and reactive oxygen species in vivo, which may account for its localization close to the mucosal tissue and expansion during inflammation. Also of note, M. schaedleri harbors a type VI secretion system and putative effector proteins and can modify gene expression in mucosal tissue, suggesting intimate interactions with its host and a possible role in inflammation. The M. schaedleri genome has been shaped by extensive horizontal gene transfer, primarily from intestinal Epsilon- and Deltaproteobacteria, indicating that horizontal gene transfer has played a key role in defining its niche in the gut ecosystem. IMPORTANCE Shifts in gut microbiota composition have been associated with intestinal inflammation, but it remains unclear whether inflammation-associated bacteria are commensal or detrimental to their host. Here, we studied the lifestyle of the gut bacterium Mucispirillum schaedleri, which is associated with inflammation in widely used mouse models. We found that M. schaedleri has specialized systems to handle oxidative stress during inflammation. Additionally, it expresses secretion systems and effector proteins and can modify the mucosal gene expression of its host. This suggests that M. schaedleri undergoes intimate interactions with its host and may play a role in inflammation. The insights presented here aid our understanding of how commensal gut bacteria may be involved in altering susceptibility to disease.

Genome-guided design of a defined mouse microbiota that confers colonization resistance against Salmonella enterica serovar Typhimurium.

Protection against enteric infections, also termed colonization resistance, results from mutualistic interactions of the host and its indigenous microbes. The gut microbiota of humans and mice is highly diverse and it is therefore challenging to assign specific properties to its individual members. Here, we have used a collection of murine bacterial strains and a modular design approach to create a minimal bacterial community that, once established in germ-free mice, provided colonization resistance against the human enteric pathogen Salmonella enterica serovar Typhimurium (S. Tm). Initially, a community of 12 strains, termed Oligo-Mouse-Microbiota (Oligo-MM12), representing members of the major bacterial phyla in the murine gut, was selected. This community was stable over consecutive mouse generations and provided colonization resistance against S. Tm infection, albeit not to the degree of a conventional complex microbiota. Comparative (meta)genome analyses identified functions represented in a conventional microbiome but absent from the Oligo-MM12. By genome-informed design, we created an improved version of the Oligo-MM community harbouring three facultative anaerobic bacteria from the mouse intestinal bacterial collection (miBC) that provided conventional-like colonization resistance. In conclusion, we have established a highly versatile experimental system that showed efficacy in an enteric infection model. Thus, in combination with exhaustive bacterial strain collections and systems-based approaches, genome-guided design can be used to generate insights into microbe-microbe and microbe-host interactions for the investigation of ecological and disease-relevant mechanisms in the intestine.