Premium
High‐fat diet–induced alterations to gut microbiota and gut‐derived lipoteichoic acid contributes to the development of enteric neuropathy
Author(s) -
Nyavor Yvonne,
Brands Catherine R.,
May George,
Kuther Sydney,
Nicholson Jessica,
Tiger Kathryn,
Tesnohlidek Abigail,
Yasuda Allysha,
Starks Kiefer,
Litvinenko Diana,
Linden David R.,
Bhattarai Yogesh,
Kashyap Purna C.,
Forney Larry J.,
Balemba Onesmo B.
Publication year - 2020
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13838
Subject(s) - lipoteichoic acid , myenteric plexus , medicine , gut flora , biology , ileum , enteric nervous system , endocrinology , duodenum , immunohistochemistry , bacteria , biochemistry , staphylococcus aureus , genetics
Background High‐fat diet, microbial alterations and lipopolysaccharide (LPS) are thought to cause enteric diabetic neuropathy and intestinal dysmotility. However, the role of the gut microbiota, lipoteichoic acid (LTA) from Gram‐positive bacteria and short‐chain fatty acids (SCFAs) in the development of diabetic enteric neuropathy and intestinal dysmotility is not well understood. Our aim was to examine the role of the gut microbiota, LTA and SCFAs in the development of diabetic enteric neuropathy and intestinal dysmotility. Methods We fed germ‐free (GF) and conventionally raised (CR) mice either a high‐fat (HFD) or standard chow diet (SCD) for 8 weeks. We analyzed the microbial community composition in CR mice using 16S rRNA sequencing and damage to myenteric neurons using immunohistochemistry. We also studied the effects of LPS, LTA, and SCFAs on duodenal muscularis externa contractions and myenteric neurons using cultured preparations. Key Results High‐fat diet ingestion reduced the total number and the number of nitrergic myenteric neurons per ganglion in the duodenum of CR but not in GF‐HFD mice. GF mice had fewer neurons per ganglion compared with CR mice. CR mice fed a HFD had increased abundance of Gram‐positive bacteria. LTA and LPS did not affect the frequency of duodenal muscularis contractions after 24 hours of cultured but reduced the density of nitrergic myenteric neurons and increased oxidative stress and TNFα production in myenteric ganglia. SCFAs did not affect muscularis contractions or injure myenteric neurons. Conclusions & Inferences Gut microbial alterations induced increase in Gram‐positive bacterial LTA may contribute to enteric neuropathy.