An Immunomodulatory Molecule of Symbiotic Bacteria Directs Maturation of the Host Immune System

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell (Impact Factor: 32.24). 08/2005; 122(1):107-18. DOI: 10.1016/j.cell.2005.05.007
Source: PubMed


The mammalian gastrointestinal tract harbors a complex ecosystem consisting of countless bacteria in homeostasis with the host immune system. Shaped by evolution, this partnership has potential for symbiotic benefit. However, the identities of bacterial molecules mediating symbiosis remain undefined. Here we show that, during colonization of animals with the ubiquitous gut microorganism Bacteroides fragilis, a bacterial polysaccharide (PSA) directs the cellular and physical maturation of the developing immune system. Comparison with germ-free animals reveals that the immunomodulatory activities of PSA during B. fragilis colonization include correcting systemic T cell deficiencies and T(H)1/T(H)2 imbalances and directing lymphoid organogenesis. A PSA mutant of B. fragilis does not restore these immunologic functions. PSA presented by intestinal dendritic cells activates CD4+ T cells and elicits appropriate cytokine production. These findings provide a molecular basis for host-bacterial symbiosis and reveal the archetypal molecule of commensal bacteria that mediates development of the host immune system.

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    • "Indeed , the relatively large genome of Bacteroides enables these microorganisms to behave both as beneficial and harmful bacteria depending on the host environmental conditions. In this way , the capsular polysaccharide of certain strains of Bacteroides fragilis can contribute to the development and maturation of the host immune system ( Mazmanian et al. , 2005 ) but is also an important virulence determinant of this bacterium ( Wexler , 2007 ). Bacteroides is an anaerobic , bile - resistant , non - spore - forming , and Gram - negative rod . "
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    ABSTRACT: Bacteroides is among the most abundant microorganism inhabiting the human intestine. They are saccharolytic bacteria able to use dietary or host-derived glycans as energy sources. Some Bacteroides fragilis strains contribute to the maturation of the immune system but it is also an opportunistic pathogen. The intestine is the habitat of most Bifidobacterium species, some of whose strains are considered probiotics. Bifidobacteria can synthesize exopolysaccharides (EPSs), which are complex carbohydrates that may be available in the intestinal environment. We studied the metabolism of B. fragilis when an EPS preparation from bifidobacteria was added to the growth medium compared to its behavior with added glucose. 2D-DIGE coupled with the identification by MALDI-TOF/TOF evidenced proteins that were differentially produced when EPS was added. The results were supported by RT-qPCR gene expression analysis. The intracellular and extracellular pattern of certain amino acids, the redox balance and the α-glucosidase activity were differently affected in EPS with respect to glucose. These results allowed us to hypothesize that three general main events, namely the activation of amino acids catabolism, enhancement of the transketolase reaction from the pentose-phosphate cycle, and activation of the succinate-propionate pathway, promote a shift of bacterial metabolism rendering more reducing power and optimizing the energetic yield in the form of ATP when Bacteroides grow with added EPSs. Our results expand the knowledge about the capacity of B. fragilis for adapting to complex carbohydrates and amino acids present in the intestinal environment.
    Frontiers in Microbiology 09/2015; 6:825. DOI:10.3389/fmicb.2015.00825 · 3.99 Impact Factor
    • "defensin) and mucus accumulation due to mucociliary defects (Round & Mazmanian, 2009). In these animals, upon re-exposure to foreign microbes, mucosal immunity started to develop (Gaboriau-Routhiau et al., 2009; Mazmanian et al., 2005; Salzman, 2011). Table 3 summarizes some studies comparing immune system components between germ-free and conventional animals. "
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    ABSTRACT: The concept of microbial content of the lung is still controversial. What make this more complicated are controversial results obtaining from different methodologies about lung microbiome and the definition of ‘‘lung sterility’’. Lungs may have very low bacteria but are not completely germ-free. Bacteria are constantly entering from the upper respiratory tract, but are then quickly being cleared. We can find bacterial DNA in the lungs, but it is much harder to ask about living bacteria. Here, we propose that if there is any trafficking of the microorganisms in the lung, it should be a ‘‘Transient But Not Resident (TBNR)’’ model. So, we speculate a "Yin Yang model" for the lung immune system and TBNR. Despite beneficial roles of microbiome on the development of lung immune system, any disruption and alteration in the microbiota composition of upper and lower airways may trigger or lead to several diseases such as asthma, chronic obstructive pulmonary disease and mustard lung disease.
    Inhalation Toxicology 08/2015; DOI:10.3109/08958378.2015.1070220 · 2.26 Impact Factor
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    • "The gut microbiota has been shown to be involved in intestinal homeostasis (Hooper and Gordon, 2001) and it is now widely believed that this complex microbial ecosystem plays a key role in human health. Metabolic syndrome, inflammatory bowel diseases and obesity are among the health impairments for which alterations in microbiota composition and gene content have been observed (Ley et al., 2005; Mazmanian et al., 2005; Qin et al., 2010). Most of the studies examining the human gut microbiota are aimed at demonstrating the health benefits that arise from modulating the microbial communities in the GI tract (Gibson and Roberfroid, 1995; Looijer-van Langen and Dieleman, 2009). "
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    ABSTRACT: Gut microbiota richness and stability are important parameters in host-microbe symbiosis. Diet modification, notably using dietary fibers, might be a way to restore a high richness and stability in the gut microbiota. In this work, during a six week nutritional trial, 19 healthy adults consumed a basal diet supplemented with 10 or 40 g dietary fiber per day for five days, followed by 15-day washout periods. Fecal samples were analyzed by a combination of 16S rRNA gene pyrosequencing, intestinal cell genotoxicity assay, metatranscriptomics sequencing approach and short chain fatty analysis. This short-term change in the dietary fiber level did not have the same impact for all individuals but remained significant within each individual gut microbiota at genus level. Higher microbiota richness was associated with higher microbiota stability upon increased dietary fiber intake. Increasing fiber modulated the expression of numerous microbiota metabolic pathways such as glycan metabolism, with genes encoding carbohydrate-active enzymes active on fiber or host glycans. High microbial richness was also associated with high proportions of Prevotella and Coprococcus species and high levels of caproate and valerate. This study provides new insights on the role of gut microbial richness in healthy adults upon dietary changes and host microbes' interaction. This article is protected by copyright. All rights reserved.
    Environmental Microbiology 07/2015; DOI:10.1111/1462-2920.13006 · 6.20 Impact Factor
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