Author Response: Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease.

Abstract

We are grateful for the comment on our study.1 We are pleased to know that short-chain fatty acids (SCFAs), especially butyrate, in the intestine could stimulate the colonization of curli-producing Escherichia coli . Curli are functional amyloids produced by gut microbes and act as cross–beta-sheet amyloid polymers to assist bacterial cells in binding to one another to form biofilm.2 Curli participate in the intracellular self-assembly process of pathologic human amyloids, including α-synuclein, leading to proteopathy and the promotion of intestinal inflammation through toll-like receptors (TLRs), or mapranosis.3 A study implanting curli-producing E. coli in germ-free α-synuclein-overexpressing mice resulted in α-synuclein aggregations and neuroinflammation, with an increased expression of tumor necrosis factor alpha (TNFα).4 This Parkinson disease (PD)–like neuropathology was reversed in mice colonized with a curli-deficient E. coli strain, supporting that gut microbial amyloids can exacerbate gut and neuropathology of PD.4 These observations are compatible with recent evidence that intestinal inflammation promotes PD neuropathology through activating TLRs and TNFα-mediated neuroinflammation.5 Furthermore, there are many members of the microbiome capable of producing functional amyloids, including Klebsiella species, for which abundance has a positive correlation between the plasma butyrate levels in patients with PD in our study.1 SCFAs may play a pivotal role in the gut-brain communication of the PD process.