Crosstalk between Muscularis Macrophages and Enteric Neurons Regulates Gastrointestinal Motility

Müller, Paul; Koscsó, Balázs; Rajani, Gaurav Manohar; Stevanovic, Korey; Berres, ML; Hashimoto, Daigo; Mortha, Arthur; Leboeuf, Marylène; Li, Xiu Min; Mucida, Daniel; Stanley, E. Richard; Dahan, Stéphanie; Margolis, Kara Gross; Gershon, Michael D.; Mérad, Miriam; Bogunovic, Milena

doi:10.1016/j.cell.2014.04.050

Cited by 526 publications

(546 citation statements)

References 66 publications

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“…These findings are consistent with hyper‐reactive colonic phenotype after antibiotic treatment (Muller et al. 2014), and indicate that gut microbes can significantly impact the gut neuromuscular apparatus responses.…”

Section: Resultsmentioning

confidence: 99%

Mutual reinforcement of pathophysiological host‐microbe interactions in intestinal stasis models

Touw

Ringus

Hubert

et al. 2017

Physiological Reports

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Chronic diseases arise when there is mutual reinforcement of pathophysiological processes that cause an aberrant steady state. Such a sequence of events may underlie chronic constipation, which has been associated with dysbiosis of the gut. In this study we hypothesized that assemblage of microbial communities, directed by slow gastrointestinal transit, affects host function in a way that reinforces constipation and further maintains selection on microbial communities. In our study, we used two models – an opioid‐induced constipation model in mice, and a humanized mouse model where germ‐free mice were colonized with stool from a patient with constipation‐predominant irritable bowel syndrome (IBS‐C) in humans. We examined the impact of pharmacologically (loperamide)‐induced constipation (PIC) and IBS‐C on the structural and functional profile of the gut microbiota. Germ‐free (GF) mice were colonized with microbiota from PIC donor mice and IBS‐C patients to determine how the microbiota affects the host. PIC and IBS‐C promoted changes in the gut microbiota, characterized by increased relative abundance of Bacteroides ovatus and Parabacteroides distasonis in both models. PIC mice exhibited decreased luminal concentrations of butyrate in the cecum and altered metabolic profiles of the gut microbiota. Colonization of GF mice with PIC‐associated mice cecal or human IBS‐C fecal microbiota significantly increased GI transit time when compared to control microbiota recipients. IBS‐C‐associated gut microbiota also impacted colonic contractile properties. Our findings support the concept that constipation is characterized by disease‐associated steady states caused by reinforcement of pathophysiological factors in host‐microbe interactions.

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Section: Resultsmentioning

confidence: 99%

Mutual reinforcement of pathophysiological host‐microbe interactions in intestinal stasis models

Touw

Ringus

Hubert

et al. 2017

Physiological Reports

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“…4C). These data suggest a previously unknown connection between innate immune recognition and the regulation of smooth muscle differentiation and contribute to an emerging role of the innate immune system and the microbiota in intestinal motility (49,50). Neonatal mast cell homeostasis.…”

Section: Resultsmentioning

confidence: 99%

Analysis of gene–environment interactions in postnatal development of the mammalian intestine

Rakoff-Nahoum

Kong

Kleinstein

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Unlike mammalian embryogenesis, which takes place in the relatively predictable and stable environment of the uterus, postnatal development can be affected by a multitude of highly variable environmental factors, including diet, exposure to noxious substances, and microorganisms. Microbial colonization of the intestine is thought to play a particularly important role in postnatal development of the gastrointestinal, metabolic, and immune systems. Major changes in environmental exposure occur right after birth, upon weaning, and during pubertal maturation into adulthood. These transitions include dramatic changes in intestinal contents and require appropriate adaptations to meet changes in functional demands. Here, we attempt to both characterize and provide mechanistic insights into postnatal intestinal ontogeny. We investigated changes in global intestinal gene expression through postnatal developmental transitions. We report profound alterations in small and large intestinal transcriptional programs that accompany both weaning and puberty in WT mice. Using myeloid differentiation factor 88 (MyD88)/TIR-domain-containing adapter-inducing interferon-β (TRIF) double knockout littermates, we define the role of toll-like receptors (TLRs) and interleukin (IL)-1 receptor family member signaling in postnatal gene expression programs and select ontogeny-specific phenotypes, such as vascular and smooth muscle development and neonatal epithelial and mast cell homeostasis. Metaanalysis of the effect of the microbiota on intestinal gene expression allowed for mechanistic classification of developmentally regulated genes by TLR/IL-1R (TIR) signaling and/or indigenous microbes. We find that practically every aspect of intestinal physiology is affected by postnatal transitions. Developmental timing, microbial colonization, and TIR signaling seem to play distinct and specific roles in regulation of gene-expression programs throughout postnatal development.

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“…Macrophages are present throughout the gut, including the muscularis externa (muscularis macrophages), where they come into close contact with components of the ENS (134,135). A recent study has shown that muscularis macrophages have a distinct marker expression profile (CX3CR1 hi MHCII hi CD11c lo CD103 -CD11b + ) and that their development and maintenance is critically dependent upon colony stimulating factor 1 (CSF1) (136). Interestingly, the ENS of CSF1-deficient animals (Csf1 op/op ) contained a higher number of neurons and had a less organized architecture, consistent with the idea that immune-related factors participate in the normal development of ENS (136).…”

Section: Microbiota Influence On Ens Developmentmentioning

confidence: 99%

Emerging roles of gut microbiota and the immune system in the development of the enteric nervous system

Kabouridis¹,

Pachnis²

2015

J. Clin. Invest.

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Crosstalk between Muscularis Macrophages and Enteric Neurons Regulates Gastrointestinal Motility

Cited by 526 publications

References 66 publications

Mutual reinforcement of pathophysiological host‐microbe interactions in intestinal stasis models

Mutual reinforcement of pathophysiological host‐microbe interactions in intestinal stasis models

Analysis of gene–environment interactions in postnatal development of the mammalian intestine

Emerging roles of gut microbiota and the immune system in the development of the enteric nervous system

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