In A, blue indicates genes up-regulated primarily by SFB, black indicates genes up-regulated primarily by BA, and red indicates genes up-regulated by both bacteria. Third, histological examination revealed the absence of gross signs of inflammation in the small intestine and colon (Fig. Relatedly, as exemplified by SFB in rodents, some intestinal symbionts show host specificity, consequent to millennia of coevolution (11, 42). Third, Th17 cells seem to have a yin–yang role in human health. One of two Th17-inducing probiotic mixes reproducibly induced the accumulation of SI-LP Th17 cells in SPF mice without significantly altering Th1 cell frequencies (Fig. Manipulations of mice are detailed in SI Materials and Methods. *P < 0.05 (Kruskal–Wallis test with Dunn’s multiple comparisons test); **P < 0.01 (Kruskal–Wallis test with Dunn’s multiple comparisons test); ***P < 0.001; (Kruskal–Wallis test with Dunn’s multiple comparisons test). Individual intestinal symbionts induce a distinct population of RORγ⁺ regulatory T cells, The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses, Induction of intestinal Th17 cells by segmented filamentous bacteria, Th17 cell induction by adhesion of microbes to intestinal epithelial cells, Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine, Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation, Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes, Intestinal interleukin-17 receptor signaling mediates reciprocal control of the gut microbiota and autoimmune inflammation, Differential roles for interleukin-23 and interleukin-17 in intestinal immunoregulation, Interleukin-23-independent IL-17 production regulates intestinal epithelial permeability, Regulation and function of innate and adaptive interleukin-17-producing cells, The IL-23-IL-17 immune axis: From mechanisms to therapeutic testing, RORγt-dependent IL-17A-producing cells in the pathogenesis of intestinal inflammation, Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis, The treatment-naive microbiome in new-onset Crohn’s disease, Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis, Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells, MUCOSAL IMMUNOLOGY. GPI, glucose-6-phosphate isomerase. Genome sequence of segmented filamentous bacteria present in the human intestine. We do not capture any email address. [Hereafter, we used either B. fragilis or Clostridium histolyticum as a control microbe because neither elicited significant SI-LP Th17 cell accumulation relative to GF mice (Fig. Therefore, we set out to identify bacterial species from the human gut microbiota capable of inducing Th17 cells in the mouse intestine. Fold change (FC)/FC plots comparing ileum tissue transcripts induced by (A) BA vs. SFB (Th17 inducing) or (B) BA vs. C. histolyticum (CH; Th17 noninducing). Our in vivo data are in concert with findings on cultured human immunocytes (61). Control of pathogens and pathobionts by the gut microbiota, Human nutrition, the gut microbiome and the immune system, The microbiota in adaptive immune homeostasis and disease, Induction of colonic regulatory T cells by indigenous Clostridium species, Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota, Identifying gut microbe-host phenotype relationships using combinatorial communities in gnotobiotic mice, MUCOSAL IMMUNOLOGY. Recent studies have shown that gut Th17 cells in SFB-bearing hosts are specific for SFB-derived antigens (34, 35). USA.gov. They secrete the cytokines IL-17A, IL-17F, and IL-22, which induce the production of antimicrobial peptides and tight junction proteins from intestinal epithelial cells, thereby buttressing gut barrier integrity (15⇓–17). To assess the role of symbiont-induced Th17 populations in autoimmune arthritis, we gavaged SPF K/BxN mice with B. adolescentis, C. histolyticum, SFB, or PBS. Colonization of the ileum by SFB induced changes in host gene expression and accelerated epithelial cell turnover. SPF mice from Jax were SFB− or colonized with SFB.

GSE87676, GSE87678, and GSE89261). Data are plotted as the average fluorescence from six to eight total images from two to three fields of view per section from two to four mice per microbe.

Hence, fluctuations in the human microbiome are likely to exert important effects on host mucosal defenses and the development of inflammatory conditions, in part via modulation of Th17 responses. Normalized bacterial fluorescence vs. distance from the epithelial surface of the terminal ileum (Il) from mice monocolonized as indicated. Analysis of normalized microarray data was conducted using MultiplotStudio v1.5.29 and GENE-E (www.broadinstitute.org/cancer/software/GENE-E/). Briefly, sections were deparaffinized using EZ-DeWax Solution (BioGenex) and washed successively with 100% ethanol, PBS, and hybridization buffer (20 mM Tris⋅HCl, 0.9 M NaCl, 0.01% SDS, pH 7.4). This site needs JavaScript to work properly. Microarray or RNA sequencing analysis was performed on whole ileal tissue, S-IECs, or SI-LP CD4+ T cells of monocolonized mice. P values are indicated to the right. Antigen presentation assays are detailed in SI Materials and Methods. Scoring method is detailed in SI Materials and Methods. The authors declare no conflict of interest. Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/.

Intestinal tissues were fixed in Carnoy’s solution (Electron’s Microscopy Sciences), embedded in paraffin, sectioned, and stained for bacteria. (C) Antiglucose-6-phosphate isomerase titers 11–13 d after initial bacterial gavage. Nature Reviews Rheumatology 7, 2011, 569-578, doi: 10.1038/nrrheum.2011.121 (Open Access) (Notizen nicht allgemeinverständlich aufbereitet; Abstract bereits im Artikel über Zusammenhänge zwischen Parodontitis und AIE zusammengefasst). B. adolescentis (BA) exacerbates K/BxN arthritis. B. adolescentis-specific Th17 responses were detected only in mice colonized with B. adolescentis but not in GF or B. fragilis-colonized mice (Fig. 1C). 2020 Aug 14;11:1783. doi: 10.3389/fimmu.2020.01783. (C) Frequencies of (Upper) Th17 and (Lower) Th1 cells in various tissues of mice colonized as indicated. SFB and B. adolescentis seemed to mobilize distinct cell types and transcriptional programs to induce Th17 responses. Colonization of the ileum by SFB induced changes in host gene expression and accelerated epithelial cell turnover. Die Bakterien in unserem Darm wiegen etwa 3 Pfund. IL-17A production was markedly enhanced on restimulation by B. adolescentis lysate to levels comparable with those provoked by activation with phorbol 12-myristate 13-acetate (PMA) plus ionomycin but was not augmented by restimulation by B. fragilis or SFB lysates (Fig. Mean ± SEM. Mean ± SEM. 5 and Tables S1–S6) were determined as follows: SFB-specific transcripts − fold change (FC; SFB/GF) > 1.5, FC (SFB/BA) > 1.2, P < 0.05 followed by manual curation on the FC/FC plot to remove transcripts lying on the SFB vs. BA diagonal; BA specific − FC (BA/GF) > 1.2, FC (BA/SFB) and FC (BA/Clostridium histolyticum) > 1.2, P < 0.05; both SFB and BA − FC (SFB/GF) > 1.5 and FC (BA/GF) > 1.5.

3B). was supported by a fellowship from the Boehringer Ingelheim Fonds. RV-protecting microbiota were interrogated by heat, filtration, and antimicrobial agents, followed by limiting dilution transplant to germ-free mice and microbiome analysis. (B) Data in A plotted as SI-LP Th17 vs. colonic RORγt+ Treg frequencies. P value was not significant for all comparisons (Kruskal–Wallis test and Dunn’s multiple comparisons test). We also tested three of the probiotic preparations in SPF-housed mice, given their complex, more natural microbiotas. eCollection 2020. BF, B. fragilis; Ce, cecum; CH, C. histolyticum; Co, colon; IEL, intraepithelial lymphocyte layer; ILN, inguinal lymph node; MLN, mesenteric lymph nodes; PP, Peyer’s patches; SI, small intestine. BA and other bifidobacterial species are represented as white bars. Thank you for your interest in spreading the word on PNAS. Furthermore, dysbiosis is concomitant with new-onset, treatment-naïve IBD and RA, implying a potential etiological role for the intestinal microbiota (21, 22). 4A). 6C). 1 A and B). SFB: Beherrschung von Unsicherheit in lasttragenden Systemen des Maschinenbaus Darmstadt 2009: 806: SFB: Unser Weg nach Europa: Kultur-Umwelt Interaktion und menschliche Mobilität im Späten Quartär Köln 2009: 814: SFB Incubation of RV with SFB-containing feces reduced infectivity in vitro, suggesting direct neutralization of RV. Therefore, B. adolescentis seems to be a bona fide intestinal symbiont akin to SFB in mice, capable of peaceful coexistence in the gut of a healthy host, despite its profound impact on the Th17 compartment. To assess cytokine production, we restimulated cells with 10 ng/mL phorbol 12-myristate 13-acetate (Sigma) and 1 μM ionomycin (Sigma) in the presence of GolgiPlug (BD Biosciences) for 3.5 h at 37 °C. ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection, https://doi.org/10.1016/j.cell.2019.09.028. (E–G) Frequencies of (E) IL-17A–producing γδ T cells, (F) IL-22–producing Thy1+ RORγt+ type 3 innate lymphoid cells (ILC3s), and (G) IL-17A–producing ILC3s in various tissues of mice colonized as indicated. Many of these disorders in both mice and humans are also associated with intestinal dysbiosis (21, 22). *P < 0.05 (Kruskal–Wallis test and Dunn’s multiple comparisons test). Please enable it to take advantage of the complete set of features! A recent study showed that a consortium of 20 symbionts from the feces of an IBD patient could induce Th17 cells in mice but failed to identify the active microbes in healthy people (11). 1E) (8). 7A) comparing values from GF mice. Bacterial composition of probiotic formulations used in this study. B. adolescentis was found in both the gut mucosa and lumen, with the overall bacterial load in the lumen progressively increasing from the duodenum to the colon, reflecting the distribution of overall bacterial burden in SPF mice (38) (Fig. Bacterial composition of probiotics is listed in Table S7. COVID-19 is an emerging, rapidly evolving situation.

With age, the frequency of bifidobacteria in the gut wanes, and the dominant species change, although members of the genus remain a substantial component in the adult (48, 49). Inoculation of specific-pathogen–free (SPF) mice with B. adolescentis recapitulated the immunologic phenotypes observed in monocolonized mice, augmenting Th17 frequencies in the SI-LP while leaving Th1 responses intact, in contrast to the lack of a significant response to a control microbe, Bacteroides fragilis (Fig. (A–D) Myeloid cells. However, microbiota-dependent Th17 responses have been implicated in IBD and other extraintestinal autoimmune disorders, including psoriasis, multiple sclerosis, and RA. L.K. The capacity for tight association with the epithelium may thus represent a conserved feature of Th17 cell-inducing microbes. BA and related species are enriched in the microbiotas of IBD patients. The aim of this study was to verify whether PCR methods could be used for the detection of SFB in biopsy of …



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