Microbiota from Exercise Mice Counteracts High-Fat High-Cholesterol Diet-Induced Cognitive Impairment in C57BL/6 Mice

Abstract

Gut microbes may be the critical mediators for the cognitive enhancing effects of exercise. Via fecal microbiota transplantation (FMT), this study is aimed at determining the mechanism of how voluntary exercise improved learning and memory ability impairment post a high-fat, high-cholesterol (HFHC) diet. The learning and memory abilities assessed via the Morris water maze in the FMT recipient group of voluntary exercising mice were improved compared to sedentary group. 16S rRNA gene sequencing results indicated that exercise-induced changes in gut microbiota distribution were transmissible, mainly in terms of elevated Lactobacillus, Lactobacillus, and Eubacterium nodatum, as well as decreased Clostrida_UCG-014 and Akkermansia after FMT. The neuroprotective effects of FMT were mainly related to the improved insulin signaling pathway (IRS2/PI3K/AKT) and mitochondrial function; inhibition of AQP4; decreased p-Tau at serine 396 and 404; increased BDNF, PSD95, and synaptophysin in the hippocampus; and also decreased HDAC2 and HDAC3 protein expressions in the nuclear and cytoplasmic fractions of the hippocampus. The findings of qRT-PCR suggested that exercise-induced gut microbes, on the one hand, elevated GPR109A and decreased GPR43 and TNF-α in the hippocampus. On the other hand, it increased GPR109A and GPR41 expressions in the proximal colon tissue. In addition, total short-chain fatty acid (SCFA), acetic acid, propionic acid, isobutyric acid, valeric acid, and isovaleric acid contents were also elevated in the cecum. In conclusion, exercise-induced alterations in gut microbiota play a decisive role in ameliorating HFHC diet-induced cognitive deficits. FMT treatment may be a new considerable direction in ameliorating cognitive impairment induced by exposure to HFHC diet.

Akkermansia muciniphilaattenuated lipopolysaccharide-induced acute lung injury by modulating the gut microbiota and SCFAs in mice

“…Klebsiella proliferate abnormally and colonize the gut, aggravating the inflammation in inflammatory bowel disease. 54 Interestingly, well-known SCFA-producing bacteria, including Lachnospiraceae _NK4A136_group, 55 Lactobacillus , 56 Roseburia , 57 and ASF356, 58 are inversely related to systemic inflammation. In addition, we found that treatment with A. muciniphila caused a significant elevation in the levels of SCFAs, such as acetic acid, propionic acid, isovaleric acid, butyric acid, isobutyric acid, and valeric acid.…”

Atherosclerosis, gut microbiome, and exercise in a meta-omics perspective: a literature review

“…Although the specific mechanisms by which SCFAs cause these effects are currently unknown, they still provide mechanistic insights into the treatment of AS by exercise. 16S rRNA sequencing as well as metabolomics analysis of fecal samples from mice after exercise intervention showed a significant increase in the total amount of SCFAs in the cecum ( Li et al, 2023 ). This finding reaffirms that exercise can affect the course of AS by influencing the gut microbiome.…”

“…Lower-intensity but sustained exercise can effectively reduce inflammation ( Paolucci et al, 2018 ), and this process may also be closely linked to the gut microbiome. SCFAs, for example, as described above, have regulatory roles in several signaling pathways in the human body and are primarily anti-inflammatory ( He et al, 2020 ) and that SCFAs expressed by the gut microbiome significantly increases after exercise ( Li et al, 2023 ). In addition, exercise is effective in relieving chronic systemic inflammation associated with aging ( Angulo et al, 2020 ), and given the age-related nature of AS, exercise management is uniquely valuable as a preventive and therapeutic measure for AS.…”

Microbiota–gut–brain axis: the mediator of exercise and brain health

“…reported a rise in total SCFAs production in C57BL/6 mice after engaging in a voluntary wheel running program for 6 weeks (Estaki et al ., 2020 ). Furthermore, sedentary mice fed with a high-fat and high-cholesterol diet received FMT from C57BL/6J mice that underwent exercise had an increased total SCFAs concentration in their feces, as compared to those receiving FMT from sedentary animals (Li et al ., 2023 ). Among the SCFAs, butyrate seems to be notably affected by exertion.…”