Presence of Segmented Filamentous Bacteria in Human Children and Its Potential Role in the Modulation of Human Gut Immunity

Abstract

Segmented filamentous bacteria (SFB) are commensal organisms that grow by anchoring a specialized holdfast structure to the intestinal walls of a variety of animals. Interaction of SFB with Peyer’s patches in mice promotes the post-natal maturation of the immune system. We previously reported that the colonization of SFB in humans mainly occurs by 36 months of age, and is difficult to be detected afterward. In this study, we measured the level of SFB in intestinal fluids of human children. SFB were found via qPCR to represent a small fraction of the whole SFB-positive microbiota (105 SFB in 1011 total bacteria). Bacteria with filamentous segmented morphology were observed in intestinal fluids via fluorescent in situ hybridization, and from gut biopsies via scanning electron microscopy. SFB-specific DNA and peptide fragments were also identified via multiple displacement amplification PCR and mass spectrometry. There was an overall positive correlation between the presence of SFB and the titer of total secretory immunoglobulin A (sIgA), which is more apparent in intestinal fluids of the age group of 8–36 months. Afterward there was a decline of SFB in numbers correlated with a reduction of total sIgA. RT-qPCR analysis of the terminal ileal biopsies revealed that the expression of Th17 pathway genes were induced in SFB-positive samples, while the markers of T and B cell receptor signaling pathways were also upregulated. Collectively, these data suggest that SFB is a rare member of microbiota, and may play an important role in the development of human gut immunity.

Specific Commensal Bacterium Critically Regulates Gut Microbiota Osteoimmunomodulatory Actions During Normal Postpubertal Skeletal Growth and Maturation

“…SFB antigen‐specific T H 17 cells have been identified in SFB colonized mice, whereas nonspecific T H 17 cells were induced in Peyerʼs patches, isolated lymphoid follicles, and the spleen . Clinical studies have shown that SFB colonization in humans primarily occurs by 36 months of age, and the presence of SFB in terminal ileal biopsies induced T H 17 pathway genes …”

“…(30) Clinical studies have shown that SFB colonization in humans primarily occurs by 36 months of age, and the presence of SFB in terminal ileal biopsies induced T H 17 pathway genes. (24,31) SFB has immunomodulatory actions regulating the development and homeostasis of host tissues, both locally in the gut (20,21,32) and at extra-GI sites. (33)(34)(35) SFB promotes T H 17/ IL17A-mediated immunity, (20,21,(28)(29)(30) which has been shown to aggravate autoimmune conditions distant to the gut.…”

Microbial pathogen primary sequence inversely correlates with blood group antigen immunogenicity

“…When comparing our k‐medoids results to our microbial pathogen sequence correlation data, we also observed that the RBC antigen immunogenicity clusters followed a trend similar to our immunogenicity‐microbial genera correlation, raising the question of a mechanistic link. Exposure to environmental pathogens and commensal bacteria has long been implicated in shaping our immune systems in the formation of ABO‐group antibodies, and more recently to the development of antigen specific Th17‐type immune responses in mouse models of autoimmune disease, as well as a potential role in humans . These serve as just a few examples of how surrounding microbes interact with and shape our immune responses, and highlight the importance of examining this potential relationship in a prospectively‐designed, future experiment.…”

Functions of the Microbiota for the Physiology of Animal Metaorganisms

“…Increased SFB levels are associated with enhanced disease severity in a number of autoimmune disorders. SFB are also found in humans, but only in an age-dependent manner [27] and in low abundance. In humans, SFB enhance immune responses, including sIgA production and Th17 induction, and activate T and B cell signaling.…”

“…In humans, SFB enhance immune responses, including sIgA production and Th17 induction, and activate T and B cell signaling. This indicates that SFB play an important role in modulating the immune system in early life [27]. …”