Symbiotic Bacteria Direct Expression of an Intestinal Bactericidal Lectin

Cash, Heather L.; Whitham, Cecilia V.; Behrendt, Cassie L.; Hooper, Lora V.

doi:10.1126/science.1127119

Cited by 1,237 publications

(1,203 citation statements)

References 27 publications

(23 reference statements)

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“…Although commensal microbes are known to be required for induction of Reg3γ expression 17 , few specific organisms have been defined. In our recently published comprehensive analysis of the immunomodulatory capacity of taxonomically diverse commensal microbes, none of 28 bacteria assessed for small-intestinal expression of Reg3γ caused significant induction 18 .…”

Section: Main Textmentioning

confidence: 99%

Moving beyond microbiome-wide associations to causal microbe identification

Surana

Kasper

2017

Nature

205

175

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Microbiome-wide association studies have established that numerous diseases are associated with changes in the microbiota1,2. These studies typically generate a long list of commensals implicated as biomarkers of disease, with no clear relevance to disease pathogenesis1–5. If the field is to move beyond correlations and begin to address causation, an effective system is needed for refining this catalog of differentially abundant microbes and allow for subsequent mechanistic studies1,4. Herein, we demonstrate that triangulation of microbe–phenotype relationships is an effective method for reducing the noise inherent in microbiota studies and enabling identification of causal microbes. We found that gnotobiotic mice harboring different microbial communities exhibited differential survival in a colitis model. Co-housing of these mice generated animals that had hybrid microbiotas and displayed intermediate susceptibility to colitis. Mapping of microbe–phenotype relationships in parental mouse strains and in mice with hybrid microbiotas identified the bacterial family Lachnospiraceae as a correlate for protection from disease. Using directed microbial culture techniques, we discovered Clostridium immunis, a previously unknown bacterial species from this family, that—when administered to colitis-prone mice—protected them against colitis-associated death. To demonstrate the generalizability of our approach, we used it to identify several commensal organisms that induce intestinal expression of an antimicrobial peptide. Thus, we have used microbe–phenotype triangulation to move beyond the standard correlative microbiome study and identify causal microbes for two completely distinct phenotypes. Identification of disease-modulating commensals by microbe–phenotype triangulation may be more broadly applicable to human microbiome studies.

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Section: Main Textmentioning

confidence: 99%

Moving beyond microbiome-wide associations to causal microbe identification

Surana

Kasper

2017

Nature

205

175

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“…Subsequently, using transcriptional analysis, they demonstrated that B. thetaiotaomicron could modulate expression of a variety of host genes, including those involved in nutrient absorption, mucosal barrier fortification, and production of angiogenic factors (120). The line of communication from bacterium to intestinal cell can morph into a complete circle: B. thetaiotaomicron can stimulate production of RegIII␥, a bactericidal lectin, which can then bind directly to bacterial peptidoglycan in gram-positive bacteria and result in bacterial killing (53).…”

Section: Environmental Sensing Systemsmentioning

confidence: 99%

“…Also as mentioned, Paneth cell proteins may produce antibacterial peptides in response to stimulation by B. thetaiotomicron (119), and these molecules may prevent pathogens from colonizing the space. In addition, B. thetaiotomicron can induce Paneth cells to produce a bactericidal lectin, RegIII␥, which exerts its antimicrobial effect by binding to the peptidoglycan of gram-positive organisms (53).…”

Section: Limiting Colonization Of the Gi Tract By Pathogensmentioning

confidence: 99%

Bacteroides: the Good, the Bad, and the Nitty-Gritty

2007

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SUMMARY Summary: Bacteroides species are significant clinical pathogens and are found in most anaerobic infections, with an associated mortality of more than 19%. The bacteria maintain a complex and generally beneficial relationship with the host when retained in the gut, but when they escape this environment they can cause significant pathology, including bacteremia and abscess formation in multiple body sites. Genomic and proteomic analyses have vastly added to our understanding of the manner in which Bacteroides species adapt to, and thrive in, the human gut. A few examples are (i) complex systems to sense and adapt to nutrient availability, (ii) multiple pump systems to expel toxic substances, and (iii) the ability to influence the host immune system so that it controls other (competing) pathogens. B. fragilis, which accounts for only 0.5% of the human colonic flora, is the most commonly isolated anaerobic pathogen due, in part, to its potent virulence factors. Species of the genus Bacteroides have the most antibiotic resistance mechanisms and the highest resistance rates of all anaerobic pathogens. Clinically, Bacteroides species have exhibited increasing resistance to many antibiotics, including cefoxitin, clindamycin, metronidazole, carbapenems, and fluoroquinolones (e.g., gatifloxacin, levofloxacin, and moxifloxacin).

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“…Aside from AMP secretion, the production of Reg3γ critically depends on the presence of commensal bacteria. In fact, Reg3γ is one of the most upregulated genes in the intestine when germ-free mice are colonized with commensal bacteria (Cash et al, 2006). Both events, bacteria-stimulated secretion and Reg3γ induction, depend on the expression of toll-like receptors (TLRs) and their downstream adaptor protein Myd88 in Paneth cells.…”

Section: Reciprocal Interaction Between Paneth Cells and Microbesmentioning

confidence: 99%

Paneth cells: the hub for sensing and regulating intestinal flora

Zhang

Liu

2016

Sci. China Life Sci.

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The complex interplay between symbiotic bacteria and host immunity plays a key role in shaping intestinal homeostasis and maintaining host health. Paneth cells, as one of the major producers of antimicrobial peptides in the intestine under steady-state conditions, play a vital role in regulating intestinal flora. Many studies on inflammatory bowel disease (IBD)-associated genes have put Paneth cells at the center of IBD pathogenesis. In this perspective, we focus on mechanistic studies of different cellular processes in Paneth cells that are regulated by various IBD-associated susceptibility genes, and we discuss the hypothesis that Paneth cells function as the central hub for sensing and regulating intestinal flora in the maintenance of intestinal homeostasis. inflammatory bowel disease, Paneth cell, commensal bacteria, intestinal homeostasisCitation:

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Symbiotic Bacteria Direct Expression of an Intestinal Bactericidal Lectin

Cited by 1,237 publications

References 27 publications

Moving beyond microbiome-wide associations to causal microbe identification

Moving beyond microbiome-wide associations to causal microbe identification

Bacteroides: the Good, the Bad, and the Nitty-Gritty

Paneth cells: the hub for sensing and regulating intestinal flora

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