High-fat diet-induced alterations to gut microbiota and gut-derived lipoteichoic acid contributes to the development of enteric neuropathy.
enteric neurons
gut bacteria
lipopolysaccharides
neuroinflammation
oxidative stress
Journal
Neurogastroenterology and motility
ISSN: 1365-2982
Titre abrégé: Neurogastroenterol Motil
Pays: England
ID NLM: 9432572
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
10
10
2019
revised:
28
01
2020
accepted:
21
02
2020
pubmed:
14
3
2020
medline:
16
7
2021
entrez:
14
3
2020
Statut:
ppublish
Résumé
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. 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. 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. Gut microbial alterations induced increase in Gram-positive bacterial LTA may contribute to enteric neuropathy.
Sections du résumé
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.
Identifiants
pubmed: 32168415
doi: 10.1111/nmo.13838
pmc: PMC7319907
mid: NIHMS1574182
doi:
Substances chimiques
Lipopolysaccharides
0
Teichoic Acids
0
lipoteichoic acid
56411-57-5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13838Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK106011
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103408
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114007
Pays : United States
Organisme : NCRR NIH HHS
ID : P20 RR016454
Pays : United States
Informations de copyright
© 2020 John Wiley & Sons Ltd.
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