A prebiotic diet intervention can restore faecal short chain fatty acids in Parkinson's Disease yet fails to restore the gut microbiome homeostasis

Abstract

ABSTRACT Despite extensive research, current treatment of Parkinson's Disease (PD) remains symptomatic and disease modifying approaches are urgently required. A promising approach is to target the gut-brain-axis by modifying the intestinal microbiota and the herein produced metabolites. We decided to test this approach by modifying key metabolites of bacterial intestinal fermentation: short chain fatty acids (SCFA), known to be decreased in PD patients. A prospective, controlled pilot study was conducted in 11 couples, with one PD patient and healthy spouse as control (CO) each. Participants followed a 4-week diet rich in dietary fibre in addition to the intake of a prebiotic sirup (Lactulose). Metagenomes and metabolites of the gut microbiota, urinary metabolites and clinical characteristics were assessed. The short-term dietary intervention significantly augmented gastrointestinal SCFA production, likely associated with increased Bifidobacteria spp. PD associated gastrointestinal symptoms improved with increasing SCFA levels. The pre-existing bacterial dysbiosis associated with PD, such as depletion of genera Blautia, Dorea, and Erysipelatoclostridium in PD, persisted within the study period. Some pathobionts, i.e. Klebsiella, were reduced after the intervention. Bacterial metabolite composition (both faecal and urine metabolomes) shifted towards the composition of the healthy control in PD after the intervention. Among these brain-relevant gut metabolic functions improved in PD patients, such as S-Adenosyl methionine (SAM), 3,4-Dihydroxyphenylacetic acid (DOPAC), Glutathione (GSH), Tryptophan and inositol related changes, involved in neuroprotective and antioxidant pathways. Despite the small cohort size and short-term study period a minor dietary intervention was sufficient to improve gastrointestinal symptoms in PD and altered metabolic parameters in a presumed neuroprotective manner, warranting further investigation in larger cohorts.