Human gut symbiont Roseburia hominis promotes and regulates innate immunity

© 2017 Patterson, Mulder, Travis, Lan, Cerf-Bensussan, Gaboriau-Routhiau, Garden, Logan, Delday, Coutts, Monnais, Ferraria, Inoue, Grant and Aminov. Objective: Roseburia hominis is a flagellated gut anaerobic bacterium belonging to the Lachnospiraceae family within the Firmicutes phylum. A significant decrease of R. hominis colonization in the gut of ulcerative colitis patients has recently been demonstrated. In this work, we have investigated the mechanisms of R. hominis-host cross talk using both murine and in vitro models. Design: The complete genome sequence of R. hominis A2-183 was determined. C3H/HeN germ-free mice were mono-colonized with R. hominis, and the host-microbe interaction was studied using histology, transcriptome analyses and FACS. Further investigations were performed in vitro and using the TLR5KO and DSS-colitis murine models. Results: In the bacterium, R. hominis, host gut colonization upregulated genes involved in conjugation/mobilization, metabolism, motility, and chemotaxis. In the host cells, bacterial colonization upregulated genes related to antimicrobial peptides, gut barrier function, toll-like receptors (TLR) signaling, and T cell biology. CD4 + CD25 + FoxP3 + T cell numbers increased in the lamina propria of both mono-associated and conventional mice treated with R. hominis. Treatment with the R. hominis bacterium provided protection against DSS-induced colitis. The role of flagellin in host-bacterium interaction was also investigated. Conclusion: Mono-association of mice with R. hominis bacteria results in specific bidirectional gene expression patterns. A set of genes thought to be important for host colonization are induced in R. hominis, while the host cells respond by strengthening gut barrier function and enhancing Treg population expansion, possibly via TLR5-flagellin signaling. Our data reveal the immunomodulatory properties of R. hominis that could be useful for the control and treatment of gut inflammation

Bacteria isolated from lung modulate asthma susceptibility in mice

Asthma is a chronic, non-curable, multifactorial disease with increasing incidence in industrial countries. This study evaluates the direct contribution of lung microbial components in allergic asthma in mice. Germ-Free and Specific-Pathogen-Free mice display similar susceptibilities to House Dust Mice-induced allergic asthma, indicating that the absence of bacteria confers no protection or increased risk to aeroallergens. In early life, allergic asthma changes the pattern of lung microbiota, and lung bacteria reciprocally modulate aeroallergen responsiveness. Primo-colonizing cultivable strains were screened for their immunoregulatory properties following their isolation from neonatal lungs. Intranasal inoculation of lung bacteria influenced the outcome of allergic asthma development: the strain CNCM I 4970 exacerbated some asthma features whereas the pro-Th1 strain CNCM I 4969 had protective effects. Thus, we confirm that appropriate bacterial lung stimuli during early life are critical for susceptibility to allergic asthma in young adults

Human gut symbiont Roseburia hominis promotes and regulates innate immunity

© 2017 Patterson, Mulder, Travis, Lan, Cerf-Bensussan, Gaboriau-Routhiau, Garden, Logan, Delday, Coutts, Monnais, Ferraria, Inoue, Grant and Aminov. Objective: Roseburia hominis is a flagellated gut anaerobic bacterium belonging to the Lachnospiraceae family within the Firmicutes phylum. A significant decrease of R. hominis colonization in the gut of ulcerative colitis patients has recently been demonstrated. In this work, we have investigated the mechanisms of R. hominis-host cross talk using both murine and in vitro models. Design: The complete genome sequence of R. hominis A2-183 was determined. C3H/HeN germ-free mice were mono-colonized with R. hominis, and the host-microbe interaction was studied using histology, transcriptome analyses and FACS. Further investigations were performed in vitro and using the TLR5KO and DSS-colitis murine models. Results: In the bacterium, R. hominis, host gut colonization upregulated genes involved in conjugation/mobilization, metabolism, motility, and chemotaxis. In the host cells, bacterial colonization upregulated genes related to antimicrobial peptides, gut barrier function, toll-like receptors (TLR) signaling, and T cell biology. CD4 + CD25 + FoxP3 + T cell numbers increased in the lamina propria of both mono-associated and conventional mice treated with R. hominis. Treatment with the R. hominis bacterium provided protection against DSS-induced colitis. The role of flagellin in host-bacterium interaction was also investigated. Conclusion: Mono-association of mice with R. hominis bacteria results in specific bidirectional gene expression patterns. A set of genes thought to be important for host colonization are induced in R. hominis, while the host cells respond by strengthening gut barrier function and enhancing Treg population expansion, possibly via TLR5-flagellin signaling. Our data reveal the immunomodulatory properties of R. hominis that could be useful for the control and treatment of gut inflammation

The microbiota regulates type 2 immunity through RORγt⁺ T cells.

Changes to the symbiotic microbiota early in life, or the absence of it, can lead to exacerbated type 2 immunity and allergic inflammations. While it is unclear how the microbiota regulates type 2 immunity, it is a strong inducer of pro-inflammatory T helper (Th) 17 cells and regulatory T cells (Tregs) in the intestine. Here, we report that microbiota-induced Tregs express the nuclear hormone receptor RORγt and differentiate along a pathway that also leads to Th17 cells. In the absence of RORγt(+) Tregs, Th2-driven defense against helminths is more efficient while Th2-associated pathology is exacerbated. Thus, the microbiota regulates type 2 responses through the induction of "type 3" RORγt(+) Tregs and Th17 cells and acts as a key factor in balancing immune responses at mucosal surfaces

Growth and host interaction of mouse segmented filamentous bacteria in vitro

manuscrit déposé dans PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102327/The gut microbiota plays a crucial role in the maturation of the intestinal mucosal immune system of its host(1,2). Within the thousand bacterial species present in the intestine, the symbiont segmented filamentous bacterium(SFB) is unique in its ability to potently stimulate the post-natal maturation of the B-and T-cell compartments and induce a striking increase in the small-intestinal Th17 responses(3-5). Unlike other commensals, SFB intimately attaches to absorptive epithelial cells in the ileum and cells overlying Peyer's patches(6,7). This colonization does not result in pathology; rather, it protects the host from pathogens(4). Yet, little is known about the SFB-host interaction that underlies the important immunostimulatory properties of SFB, because SFB have resisted in vitro culturing for more than 50 years. Here we grow mouse SFB outside their host in an SFB-host cell co-culturing system. Single-celled SFB isolated from mono-colonized mice undergo filamentation, segmentation, and differentiation to release viable infectious particles, the intracellular offspring, which can colonize mice to induce signature immune responses. In vitro, intracellular offspring can attach to mouse and human host cells and recruit actin. In addition, SFB can potently stimulate the upregulation of host innate defence genes, inflammatory cytokines, and chemokines. In vitro culturing thereby mimics the in vivo niche, provides new insights into SFB growth requirements and their immunostimulatory potential, and makes possible the investigation of the complex developmental stages of SFB and the detailed dissection of the unique SFB-host interaction at the cellular and molecular levels

Gut and Breast Milk Microbiota and Their Role in the Development of the Immune Function

The gastrointestinal immune system consists of both innate and adaptive immunity. The microbiota plays an important role in gastrointestinal immune function. In newborns, the maternal gut microbiota may either come across into the amniotic fluid or secrete factors that enter the amniotic fluid and affect the development of oral tol- erance in utero. Adequate colonization must occur in the immediate postpartum period for the appropriate mucosal immune response since it is apparent that later attempts at colonization do not have the same impact. Human milk, being also a direct source of microbes, represents one of the main factors that play a critical role in influencing infant’s microbiota composition