Rifaximin Modifies Gut Microbiota and Attenuates Inflammation in Parkinson’s Disease: Preclinical and Clinical Studies

Abstract

Patients with Parkinson’s disease (PD) exhibit distinct gut microbiota, which may promote gut-derived inflammation. Rifaximin is a nonabsorbable antibiotic that can modify gut microbiota. The present study investigated the effect of rifaximin on gut microbiota and inflammation status in PD. The study examined the effect of long-term rifaximin treatment on in vivo transgenic PD mice (MitoPark) and short-term rifaximin treatment on patients with PD. Rifaximin treatment caused a significant change in gut microbiota in the transgenic PD mice; in particular, it reduced the relative abundance of Prevotellaceae UCG-001 and increased the relative abundance of Bacteroides, Muribaculum, and Lachnospiraceae UCG-001. Rifaximin treatment attenuated serum interleukin-1β, interleukin-6 and tumor necrosis factor-α, claudin-5 and occludin, which indicated the reduction of systemic inflammation and the protection of the blood–brain barrier integrity. The rifaximin-treated MitoPark mice exhibited better motor and memory performance than did the control mice, with lower microglial activation and increased neuronal survival in the hippocampus. In the patients with PD, 7-day rifaximin treatment caused an increase in the relative abundance of Flavonifractor 6 months after treatment, and the change in plasma proinflammatory cytokine levels was negatively associated with the baseline plasma interleukin-1α level. In conclusion, the present study demonstrated that rifaximin exerted a neuroprotective effect on the transgenic PD mice by modulating gut microbiota. We observed that patients with higher baseline inflammation possibly benefited from rifaximin treatment. With consideration for the tolerability and safety of rifaximin, randomized controlled trials should investigate the disease-modification effect of long-term treatment on select patients with PD.

What Can Inflammation Tell Us about Therapeutic Strategies for Parkinson’s Disease?

“…By taking rifaximin, a non-absorbable antibiotic, the gut microbiota can be modified. Patients with PD and higher baseline inflammation levels may have experienced benefits from taking rifaximin [252]. The negative association between ibuprofen and PD risks implies that ibuprofen has the potential to act as a neuroprotective agent against PD (see Table 2) [248].…”

The interplay between gut microbiota and the brain-gut axis in Parkinson’s disease treatment

“…Association with Non-motor Symptoms: Non-motor symptoms, including depression and anxiety, significantly detract from the quality of life for individuals with PD and often manifest prior to the disease's motor symptoms. This timing suggests a potential connection to early pathological changes within PD (13,18,20,21,24,26,28,31,33,34,36,39,42,43,45,47,50,51,53,55,58,59,61). The gut-brain axis mediates the gut microbiota's effect on mood and behavior, with specific bacterial strains producing neurotransmitters like serotonin and dopamine, crucial for mood regulation (9,13,16,18,20,22,25,27,30,32,35,37,43,45,50,52,56,58).…”

“…Dysbiosis-induced inflammation could intensify neurodegeneration, hastening cognitive deterioration (5,6,10,13,21,25,32,36,40,56,59). Additionally, neurotoxic metabolites produced by specific pathogenic bacteria might directly affect brain function, implicating gut microbiota in PD's cognitive deficits (2, 54).…”

Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside

“…Antibiotics have also been found to significantly improve motor dysfunction and alleviate neuroinflammation by increasing the relative abundance of Akkermansia and Lachnospiraceae and SCFA levels in the faeces of MPTP-induced and transgenic PD mouse models [ 172 – 174 ]. A 12-month study found that creatine and minocycline can delay the disease progression in PD patients [ 175 ].…”