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Gastroenterology. 2017 Dec;153(6):1594-1606.e2. doi: 10.1053/j.gastro.2017.08.044. Epub 2017 Sep 1.

Paneth Cell Defects Induce Microbiota Dysbiosis in Mice and Promote Visceral Hypersensitivity.

Author information

1
INRA, ToxAlim (Research Centre in Food Toxicology), team Neuro-Gastroenterology and Nutrition, Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France.
2
Equipe Apicomplexes et Immunité Mucosale (AIM), UMR 1282 INRA/Université-Infectiologie et Santé Publique (ISP), Centre INRA Val de Loire, Nouzilly, France.
3
INRA, ToxAlim (Research Centre in Food Toxicology), team Neuro-Gastroenterology and Nutrition, Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France. Electronic address: sandrine.menard@inra.fr.

Abstract

BACKGROUND & AIMS:

Separation of newborn rats from their mothers induces visceral hypersensitivity and impaired epithelial secretory cell lineages when they are adults. Little is known about the mechanisms by which maternal separation causes visceral hypersensitivity or its relationship with defects in epithelial secretory cell lineages.

METHODS:

We performed studies with C3H/HeN mice separated from their mothers as newborns and mice genetically engineered (Sox9flox/flox-vil-cre on C57BL/6 background) to have deficiencies in Paneth cells. Paneth cell deficiency was assessed by lysozyme staining of ileum tissues and lysozyme activity in fecal samples. When mice were 50 days old, their abdominal response to colorectal distension was assessed by electromyography. Fecal samples were collected and microbiota were analyzed using Gut Low-Density Array quantitative polymerase chain reaction.

RESULTS:

Mice with maternal separation developed visceral hypersensitivity and defects in Paneth cells, as reported from rats, compared with mice without maternal separation. Sox9flox/flox-vil-Cre mice also had increased visceral hypersensitivity compared with control littermate Sox9flox/flox mice. Fecal samples from mice with maternal separation and from Sox9flox/flox-vil-cre mice had evidence for intestinal dysbiosis of the microbiota, characterized by expansion of Escherichia coli. Daily gavage of conventional C3H/HeN adult mice with 109 commensal E coli induced visceral hypersensitivity. Conversely, daily oral administration of lysozyme prevented expansion of E coli during maternal separation and visceral hypersensitivity.

CONCLUSIONS:

Mice with defects in Paneth cells (induced by maternal separation or genetically engineered) have intestinal expansion of E coli leading to visceral hypersensitivity. These findings provide evidence that Paneth cell function and intestinal dysbiosis are involved in visceral sensitivity.

KEYWORDS:

Abdominal Pain; Antimicrobial Activity; Lysozyme; Stress

PMID:
28865734
DOI:
10.1053/j.gastro.2017.08.044
[Indexed for MEDLINE]

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