The microbiota-gut-brain axis participates in chronic cerebral hypoperfusion by disrupting the metabolism of short-chain fatty acids

Abstract

Background Chronic cerebral hypoperfusion (CCH) underlies secondary brain injury following certain metabolic disorders and central nervous system (CNS) diseases. Dysregulation of the microbiota-gut-brain axis can exacerbate various CNS disorders through aberrantly expressed metabolites such as short-chain fatty acids (SCFAs). Yet, its relationship with CCH remains to be demonstrated. And if so, it is of interest to explore whether restoring gut microbiota to maintain SCFA metabolism could protect against CCH. Results Rats subjected to bilateral common carotid artery occlusion (BCCAO) as a model of CCH exhibited cognitive impairment, depressive-like behaviors, decreased gut motility, and compromised gut barrier functions. The 16S ribosomal RNA gene sequencing revealed an abnormal gut microbiota profile and decreased relative abundance of some representative SCFA producers, with the decreased hippocampal SCFAs as the further evidence. Using fecal microbiota transplantation (FMT), rats recolonized with a balanced gut microbiome acquired a higher level of hippocampal SCFAs, as well as decreased neuroinflammation when exposed to lipopolysaccharide. Healthy FMT promoted gut motility and gut barrier functions, and improved cognitive decline and depressive-like behaviors by inhibiting hippocampal neuronal apoptosis in BCCAO rats. Long-term SCFA supplementation further confirmed its neuroprotective effect in terms of relieving inflammatory response and hippocampal neuronal apoptosis following BCCAO. Conclusion Our results demonstrate that modulating the gut microbiome via FMT can ameliorate BCCAO-induced gut dysbiosis, cognitive decline, and depressive-like behaviors, possibly by enhancing the relative abundance of SCFA-producing floras and subsequently increasing SCFA levels.

Microbiota-derived metabolites as drivers of gut–brain communication

“… 84 Also, reinstating the SCFA-producing floras or administration of SCFAs inhibited hippocampal neuroinflammation and neuronal apoptosis, thus ameliorating cognitive decline and depressive-like behavior in a rat model of chronic cerebral hypoperfusion. 85 Controversially, propionic acid alone has been linked with CNS oxidative stress, astrogliosis, hyperactivity, and social behavior abnormalities in a series of rat models of ASD. 96–100 Interestingly, SCFAs had no effect on the α-synuclein aggregation in vitro , but induced aggregation in selected brain regions and promoted motor deficits in an in vivo genetic model of Parkinson’s disease.…”

Berberine mitigates intracerebral hemorrhage-induced neuroinflammation in a gut microbiota-dependent manner in mice

“…The gut microbiota has been implicated in neuroinflammation associated with several CNS diseases [29]. Chronic cerebral hypoperfusion in rats was found to adversely affect the microbiota, causing reduced levels of short-chain fatty acids and cognitive impairment, and these effects could be reversed by FMT [30]. In mice with TBI, the microbiota was found to reduce both neuroinflammation and promote neurogenesis [13].…”

Protection by -Biotics against Hypertension Programmed by Maternal High Fructose Diet: Rectification of Dysregulated Expression of Short-Chain Fatty Acid Receptors in the Hypothalamic Paraventricular Nucleus of Adult Offspring

“…Acetate, propionate, and butyrate levels in hypothalamic tissues or plasma were measured using gas chromatography-mass spectrometry (GC2030-QP2020 NX; Shimadzu, Kyoto, Japan) on an Agilent HP-FFAP capillary column (J&W Scientific, Folsom, CA, USA). SCFAs from hypothalamic samples were prepared following previously described procedures [ 47 ] with modifications. In brief, 5 mg of pooled hypothalamic sample was vortexed in phosphoric acid (0.5% v / v ) solution for 10 s, followed by homogenization for 4 min at 40 Hz.…”