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IntroductionCognitive decline is a common consequence of aging. Dietary patterns that lack fibers and are high in saturated fats worsen cognitive impairment by triggering pro-inflammatory pathways and metabolic dysfunctions. Emerging evidence highlights the neurocognitive benefits of fiber-rich diets and the crucial role of gut-microbiome-brain signaling. However, the mechanisms of this diet-microbiome-brain regulation remain largely unclear. MethodsAccordingly, we herein investigated the unexplored neuroprotective mechanisms of dietary pulses-derived resistant starch (RS) in improving aging-associated neurocognitive function in an aged (60-weeks old) murine model carrying a human microbiome. Results and discussionFollowing 20-weeks dietary regimen which included a western-style diet without (control; CTL) or with 5% w/w fortification with RS from pinto beans (PTB), black-eyed-peas (BEP), lentils (LEN), chickpeas (CKP), or inulin fiber (INU), we find that RS, particularly from LEN, ameliorate the cognitive impairments induced by western diet. Mechanistically, RS-mediated improvements in neurocognitive assessments are attributed to positive remodeling of the gut microbiome-metabolome arrays, which include increased short-chain fatty acids and reduced branched-chain amino acids levels. This microbiome-metabolite-brain signaling cascade represses neuroinflammation, cellular senescence, and serum leptin/insulin levels, while enhancing lipid metabolism through improved hepatic function. Altogether, the data demonstrate the prebiotic effects of RS in improving neurocognitive function via modulating the gut-brain axis.
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Host-microbial interactions in the metabolism of different dietary fats
Although generally presumed to be isocaloric, dietary fats can differ in their energetic contributions and metabolic effects. Here, we show how an explicit consideration of the gut microbiome and its interactions with human physiology can enrich our understanding of dietary fat metabolism. We outline how variable human metabolic responses to different dietary fats, such as altered ileal digestibility or bile acid production, have downstream effects on the gut microbiome that differentially promote energy gain and inflammation. By incorporating host-microbial interactions into energetic models of human nutrition, we can achieve greater insight into the underlying mechanisms of diet-driven metabolic disease.
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- Award ID(s):
- 1919892
- PAR ID:
- 10311249
- Date Published:
- Journal Name:
- Cell metabolism
- Volume:
- 33
- Issue:
- 5
- ISSN:
- 1550-4131
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1016/j.cmet.2021.04.011
