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

Bo Chen,Weizhong Gu,Junjie Qin,Xin Wang,Jia Li,Yoram Elitsur,Hongwei D Yu,Lanjuan Li,Fei Xu,Hong Zhao,Jian Song,Huahai Chen,Lijun Chen,Kerong Peng,Xiaoli Shu,Yeshi Yin,Mizu Jiang,Liqin Jiang,Charlie Xiang

doi:10.3389/fmicb.2018.01403

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.

Highlights

Segmented filamentous bacteria (SFB), or Candidatus Savagella (Thompson et al, 2012), have been implicated in the modulation of the host immune system (Ivanov and Littman, 2010)
Linear discriminant analysis (LDA) indicated that the genus Clostridia, Coriobacteriia, and Deltaproteobacteria were increased in SFB positive samples, while genus Bacteroides, Escherichia, and Klebsiella were increased in SFB negative samples
Lagier et al (2015) reported that in a complex ecosystem that consists of 1012 bacteria, current metagenomic studies are unable to detect bacteria at the level of 105 bacteria

Summary

INTRODUCTION

Segmented filamentous bacteria (SFB), or Candidatus Savagella (Thompson et al, 2012), have been implicated in the modulation of the host immune system (Ivanov and Littman, 2010). Jonsson (2013) using PCR, detected SFB in human ileostomy samples and Caselli’s group observed morphological SFB-like Gram-positive bacteria in histological slides of ileo-cecal valves from ulcerative colitis patients (Caselli et al, 2013). Given these pieces of evidence, humans may harbor SFB; direct evidence of human SFB is lacking and no other SFB genes, apart from the 16S rRNA gene, have been reported in human specimens. Similar to the effect from mouse SFB studies, an enhanced human immune response was observed in the SFB-positive individuals by comparing total sIgA production in the terminal ilea. In addition to the Th17 pathway genes, we found SFB colonization of human terminal ileum is associated with the activation of T and B cell receptor (BCR) signaling pathways

RESULTS

18 KSGLDQLIVK

DISCUSSION

MATERIALS AND METHODS

Findings

FISH Procedure