Targeting our second brain using prebiotics

Microbiota

 

The discovery of intestinal actors, such as enterosynes that are able to modulate the ENS-induced duodenal contraction, opens new research avenues.

Among all the intestinal factors, gut microbes and their role that they play in controlling glycaemia remain a major target. Therefore, we conducted research on the gut microbiota and demonstrated that the administration of prebiotics could modulate the microbiome and allow the identification of novel enterosynes.

The enteric nervous system (ENS) plays a key role in controlling the gut-brain axis under normal and pathological conditions, such as type 2 diabetes

Among all the intestinal factors, the understanding of the role of gut microbes in controlling glycaemia is still developed. We studied whether the modulation of gut microbiota by prebiotics could permit the identification of novel enterosynes.

Methods :

We measured the effects of prebiotics on the production of bioactive lipids in the intestine and tested the identified lipid on ENS-induced contraction and glucose metabolism. Then, we studied the signalling pathways involved and compared the results obtained in diabetic mice and in human subjects.

Results :

We found that modulating the gut microbiota with prebiotics modifies the actions of enteric neurons, thereby controlling duodenal contraction and subsequently attenuating hyperglycaemia in diabetic mice. We discovered that the signalling pathway involved in these effects depends on the synthesis of a bioactive lipid 12-hydroxyeicosatetraenoic acid (12-HETE) and the presence of mu-opioid receptors (MOR) on enteric neurons. Using pharmacological approaches, we demonstrated the key role of the MOR receptors and proliferator-activated receptor γ for the effects of 12-HETE. These findings are supported by human data showing a decreased expression of the proenkephalin and MOR messenger RNAs in the duodenum of patients with diabetes.

Conclusions :

Using a prebiotic approach, we identified enkephalin and 12-HETE as new enterosynes with a potential real benefit and safety impact on diabetic patients.

Source : Abot A, Wemelle E, Laurens C, Paquot A, Pomie N, Carper D, Bessac A, Mas Orea X, Fremez C, Fontanie M, Lucas A, Lesage J, Everard A, Meunier E, Dietrich G, Muccioli GG, Moro C, Cani PD, Knauf C. Identification of new enterosynes using prebiotics: roles of bioactive lipids and mu-opioid receptor signalling in humans and mice. Gut. 2021 Jun;70(6):1078-1087. doi: 10.1136/gutjnl-2019-320230. Epub 2020 Oct 5. PMID: 33020209; PMCID: PMC8108281.

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