Gut microbiota in dementia with Lewy bodies

Abstract

Gut microbiota and fecal bile acids were analyzed in 278 patients with α-synucleinopathies, which were comprised of 28 patients with dementia with Lewy bodies (DLB), 224 patients with Parkinson’s disease (PD), and 26 patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). Similarly to PD, short-chain fatty acids-producing genera were decreased in DLB. Additionally, Ruminococcus torques and Collinsella were increased in DLB, which were not changed in PD. Random forest models to differentiate DLB and PD showed that high Ruminococcus torques and high Collinsella, which presumably increase intestinal permeability, as well as low Bifidobacterium, which are also observed in Alzheimer’s disease, were predictive of DLB. As Ruminococcus torques and Collinsella are also major secondary bile acids-producing bacteria, we quantified fecal bile acids and found that the production of ursodeoxycholic acid (UDCA) was high in DLB. Increased UDCA in DLB may mitigate neuroinflammation at the substantia nigra, whereas neuroinflammation may not be critical at the neocortex. Theraeutic intervention to increase Bifidobacteirum and its metabolites may retard the development and progression of DLB.

Gastrointestinal disorders in Parkinson’s disease and other Lewy body diseases

“…Our recent study has shown that the abundance of SCFA-producing bacteria is decreased, and that of Akkermansia is increased in DLB 80 , as has been observed in PD 62 . In addition, the abundance of Ruminococcus torques and Collinsella is increased in DLB, but not in PD.…”

“…Thus, the mitigation of neuroinflammation is likely to be effective in the substantia nigra, but not in the cerebral cortex, where neuroinflammation may not critically aggravate neuronal cell death. DLB generally develops at the age of above 65 years 128 , and its average is higher than that of PD 80 , 128 . The lack of PD symptoms in older patients with DLB is consistent with the notion that dopaminergic neuronal cell death due to neuroinflammation at the substantia nigra is not critical in DLB.…”

“…In addition, Ruminococcus torques and Collinsella are major secondary bile acid-producing bacteria 86 . Indeed, the measurement of fecal secondary bile acids has revealed that the production of ursodeoxycholate (UDCA), a major secondary bile acid, is increased in DLB 80 . The anti-inflammatory 87 and antioxidant effects 88 of UDCA have been previously reported.…”

“…In contrast, in RBD, where Akkermansia abundance is increased but SCFA-producing bacterial abundance is not decreased, α-synuclein fibrils are formed in EECs and ENS and ascend the vagal nerve, but the lack of neuroinflammation is likely to suppress or delay the development of PD. Similarly, in DLB, neuroinflammation due to the lack of SCFAs is mitigated in the substantia nigra but not in the cortex by secondary bile acids generated by the increased abundance of Ruminococcus torques and Collinsella 80 . Indeed, intraperitoneal injection of LPS causes P2Y6 receptor-mediated activation of microglia and inflammatory neuronal loss in the substantia nigra but not in the cortex or hippocampus 127 .…”

Pterostilbene Enhances Thermogenesis and Mitochondrial Biogenesis by Activating the SIRT1/PGC‐1α/SIRT3 Pathway to Prevent Western Diet‐Induced Obesity

“…Among them, Acetatifactor is a strictly anaerobic bacteria that can produce acetate and butyrate at a certain ratio in the gut, [ 58 ] whereas Blautia is known as a SCFA‐producing bacteria. [ 59 ] Meanwhile, Parasutterella has been reported to be positively correlated to fatty‐acid biosynthesis and β‐cell failure in obesity and type 2 diabetes cohorts. [ 60 ] Nevertheless, the species in this guild and the functionalities of the guild should be further clarified.…”