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Nod1/Nod2 Receptors Modulate the Microbiota‐Gut‐Brain Axis
Author(s) -
Schneider Melinda,
Zhang Yingzhen,
Barrett Kim,
Gareau Melanie
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.857.4
Subject(s) - gut–brain axis , nod , nod1 , corticosterone , gut flora , receptor , pattern recognition receptor , biology , hippocampal formation , endocrinology , medicine , nod mice , immunology , knockout mouse , dysbiosis , innate immune system , nod2 , hormone , diabetes mellitus
An association of intestinal diseases with behavioral changes and cognitive deficits is increasingly recognized. Previous studies suggest that chronic intestinal diseases, in combination with an acute psychological stressor (water avoidance stress [WAS]), induce anxiety and memory defects. We hypothesized that innate nucleotide‐binding oligomerization domain (Nod) receptors, as modulators of homeostasis between the host immune system and microbiota, are integral microbiota‐gut‐brain axis regulators. Using Nod‐1, ‐2 double knockout (NodDKO) mice, we performed behavioral studies, qPCR analysis of stool bacterial DNA and serum corticosterone analysis. Compared to wild type (WT) controls (C57BL/6), NodDKO mice had elevated anxiety levels, (light/dark box test, p<0.001), and WAS‐induced recognition memory deficits (novel object test, p<0.001). Dysbiosis and elevated corticosterone levels (p<0.001) were also observed in NodDKO mice. To evaluate the role of the microbiota in mediating these effects, WT and NodDKO mice were co‐housed at weaning and behavior assessed. Cohousing confirmed that Nod receptors are important for non‐spatial memory and anxiety, with defects remaining despite microbiota normalization. Therefore, our study indicates that Nod receptors may serve as key signaling molecules, acting via the hypothalamic–pituitary–adrenal (HPA) axis, that modulate the microbiota‐gut‐brain axis.