Figure 11.

Scheme showing possible interaction(s) among gut microbiota, gut microbial metabolites, polyunsaturated fatty acid (PUFAs) and their metabolites [lipoxin A4 (LXA4), resolvins and protectins], and endocannabinoid system. It is possible that endocannabinoid receptors in the hypothalamus and other brain areas also play a role in DM. A stronger role for endocannabinoid system is seen in type 2 DM compared to its role in type 1 diabetes mellitus. It is likely (needs firm evidence) that gut microbiota metabolizes dietary linoleic acid and α-linolenic acid to arachidonic acid (AA) and eicosapentaneoic acid (EPA) and docosahexaenoic acid (DHA), respectively, that may enhance the formation of anti-inflammatory and antidiabetic molecules LXA4 (from AA), resolvins (from EPA and DHA), and protectins (from DHA, see Figures 7 and 8 also). AA, EPA, and DHA may enhance the proliferation of useful microbiota. Thus, there could be a two-way interaction between PUFAs and gut microbiota. PUFAs have antibiotic-like actions and so may suppress the proliferation of harmful bacteria that are associated with obesity. There could be an interaction between endocannabinoid system, gut microbiota metabolites, and hypothalamic neurotransmitters as shown in the figure.