Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a prevalent type of neurodegenerative disease. There is mounting evidence that the gut microbiota is involved in the pathogenesis of PD. Sodium butyrate (NaB) can regulate gut microbiota and improve brain functioning in neurological disorders. Hence, we examined whether the neuroprotective function of NaB on PD was mediated by the modulation of gut microbial dysbiosis and revealed its possible mechanisms. Mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days to construct the PD model. NaB gavage was given 2 h after the daily MPTP injections for 21 days. NaB improved the motor functioning of PD mice, increased striatal neurotransmitter levels, and reduced the death of dopaminergic neurons. The 16S rRNA sequencing analysis revealed that NaB restored the gut microbial dysbiosis. NaB also attenuated the intestinal barrier’s disruption and reduced serum, colon, and striatal pro-inflammatory cytokines, along with inhibiting the overactivation of glial cells, suggesting an inhibitory effect on inflammation from NaB throughout the gut–brain axis of the PD mice. Mechanistic studies revealed that NaB treatment suppressed the TLR4/MyD88/NF-kB pathway in the colon and striatum. In summary, NaB had a neuroprotective impact on the PD mice, likely linked to its regulation of gut microbiota to inhibit gut–brain axis inflammation.

Sodium butyrate activates the KATP channels to regulate the mechanism of Parkinson's disease microglia model inflammation

“…Therefore, in the current study, we treated BV2 cells with MPP + to induce PD‐like conditions in vitro. NaB has exhibited antiapoptotic properties in neurodegenerative disorders and can cause α‐syn degradation, inhibit overactivation of glial cells and inflammatory responses and ameliorate motor deficits in PD models 44–47 . In this study, we have explored the underlying mechanisms by which NaB exerts protective effects against PD‐like conditions.…”

“…NaB has exhibited antiapoptotic properties in neurodegenerative disorders and can cause α-syn degradation, inhibit overactivation of glial cells and inflammatory responses and ameliorate motor deficits in PD models. [44][45][46][47] In this study, we have explored the underlying mechanisms by which NaB exerts protective effects against PD-like conditions. NaB treatment inhibits the microglia-mediated neuroinflammation by activating the K ATP channels as indicated by following findings: After treatment with 100 μM MPP + , the morphology of BV2 wells changed from resting state to activated state.…”

Gut Microbial Metabolome and Dysbiosis in Neurodegenerative Diseases: Psychobiotics and Fecal Microbiota Transplantation as a Therapeutic Approach—A Comprehensive Narrative Review

“…For example, recent studies have shown that the gut microbiota is essential in the onset and maintenance of diseases that are related to the CNS, such as mood disorders, schizophrenia, or autism, and even with neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), or Huntington s disease, among others [55][56][57]. In addition, we now know that the certain markers of the pathology are related to an increase in intestinal permeability, called leaky gut syndrome [58].…”

“…On the other hand, it is known that the determining marker of the pathology is the presence of Lewy bodies that develop in the ENS, and this is associated with an increase in intestinal permeability [58]. Leaky gut syndrome encourages damage to this tissue to promote the inclusion of harmful substances, and is associated with the presence of dysbiosis, which would alter intestinal permeability and thus promote the occurrence of the pro-inflammatory response [177,178].…”

Frataxin Deficiency Drives a Shift from Mitochondrial Metabolism to Glucose Catabolism, Triggering an Inflammatory Phenotype in Microglia

“…It has been reported that microbiota-derived short-chain fatty acid (SCFA) butyrate enhances oxidative metabolism and uncouples Krebs cycle from glycolytic flux in immune cells (Bachem et al, 2019). Butyrate had a neuroprotective impact on mouse models of Parkinson’s disease, likely due to the downstream regulation of gut microbiota and inhibition of gut-brain axis inflammation (Guo et al, 2023). Butyrate reduces neuroinflammation and microglia activation in several experimental models of disease (Caetano-Silva et al, 2023; Huuskonen et al, 2004; Wenzel et al, 2020).…”