The Lifestyle of the Segmented Filamentous Bacterium: A Non-Culturable Gut-Associated Immunostimulating Microbe Inferred by Whole-Genome Sequencing

Abstract

Numerous microbes inhabit the mammalian intestinal track and strongly impact host physiology; however, our understanding of this ecosystem remains limited owing to the high complexity of the microbial community and the presence of numerous non-culturable microbes. Segmented filamentous bacteria (SFBs), which are clostridia-related Gram-positive bacteria, are among such non-culturable populations and are well known for their unique morphology and tight attachment to intestinal epithelial cells. Recent studies have revealed that SFBs play crucial roles in the post-natal maturation of gut immune function, especially the induction of Th17 lymphocytes. Here, we report the complete genome sequence of mouse SFBs. The genome, which comprises a single circular chromosome of 1 620 005 bp, lacks genes for the biosynthesis of almost all amino acids, vitamins/cofactors and nucleotides, but contains a full set of genes for sporulation/germination and, unexpectedly, for chemotaxis/flagella-based motility. These findings suggest a triphasic lifestyle of the SFB, which comprises two types of vegetative (swimming and epicellular parasitic) phases and a dormant (spore) phase. Furthermore, SFBs encode four types of flagellin, three of which are recognized by Toll-like receptor 5 and could elicit the innate immune response. Our results reveal the non-culturability, lifestyle and immunostimulation mechanisms of SFBs and provide a genetic basis for the future development of the SFB cultivation and gene-manipulation techniques.

Comparative analysis of the distribution of segmented filamentous bacteria in humans, mice and chickens

“…This supports the conclusion that SFB are not present in human fecal samples (Prakash et al, 2011;Sczesnak et al, 2011). There are few genes in the human gut that are similar to mouse and rat SFB genes (Kuwahara et al, 2011;Prakash et al, 2011;Sczesnak et al, 2011). The issue of whether SFB inhabit the human gut and their taxonomic relationship with their counterparts in other hosts remains to be elucidated.…”

“…These projects include one database generated from 124 individuals (Qin et al, 2010) and another generated from 139 individuals (Sczesnak et al, 2011). All searches were negative, although Kuwahara et al (2011) reported 227 sequence reads of mouse SFB that were highly homologous to human sequences. This finding could be ascribed to the fact that all individuals involved in the previous human metagenomic studies were adults between 18 and 69 years old (Qin et al, 2010).…”

Animals in a bacterial world, a new imperative for the life sciences

“…Although not all genomesize reduction occurs in symbiosis, a long history of intimate association with insects has resulted in highly reduced genomes in their intracellular symbionts; for example, the endosymbiont Candidatus Hodgkinia cicadicola of the Arizona cicada has a genome size <144 kb, smaller than that of some organelles (35). Recent studies have shown that genome reduction also occurs in segmented filamentous bacteria (Candidatus Savagella), members of the mammalian microbiota that are critical for the maturation of the immune system (36). Conversely, in Bacteroides thetaiotaomicron, another member of the mammalian intestinal microbiota, adaptation to a gut habitat rich in complex carbohydrates has driven the expansion of at least two gene families: glycan-utilization genes, which constitute 18% of this species' genome (37), and diverse sulfatases that allow B. thetaiotaomicron to digest host mucin (38).…”

The role of gut microbiota in immune homeostasis and autoimmunity

“…Identifying other microbes as Th17 inducers is especially important in humans because a recent report indicated that only a small number of reads corresponding to 0.31% of the mouse SFB genome were identified in the data set of human gut metagenome sequences, suggesting other bacteria may function as the main inducers of human Th17 cells. 41,42 Alternatively, it is possible that no detection of SFB in human is a result of the human metagenome data set not including samples from children at weaning periods. In mice, SFB colonization becomes prevalent at the weaning age.…”