Reduction of Short-Chain Fatty Acid-Producing Gut Microbiota Leads to Transition from Rapid-Eye-Movement Sleep Behavior Disorder to Parkinson’s Disease

AbstractGut dysbiosis has been reported repeatedly in Parkinson’s disease (PD), but once in rapid-eye-movement sleep behavior disorder (RBD) from Germany. Abnormal aggregation of α-synuclein fibrils causing PD possibly starts from the intestine. RBD patients frequently develop PD. Early-stage gut dysbiosis that is causally associated with PD is thus expected to be observed in RBD. We analyzed gut microbiota in 26 RBD patients and 137 controls by 16S rRNA-seq. Our RBD dataset was meta-analyzed with the German RBD dataset, and was compared with gut microbiota in 223 PD patients. Unsupervised clustering of gut microbiota by LIGER, a topic model-based tool for single-cell RNA-seq analysis, revealed four enterotypes in controls, RBD, and PD. Short-chain fatty acid (SCFA)-producing bacteria were conserved in an enterotype observed in controls and RBD, whereas they were less in enterotypes observed in PD. Genus Akkermansia and family Akkermansiaceae were consistently increased in both RBD in two countries and PD in five countries. No short-chain fatty acid (SCFA)-producing bacteria were significantly changed in RBD in two counties. In contrast, we previously reported that recognized and putative SCFA-producing genera Faecalibacterium, Roseburia, and Lachnospiraceae ND3007 group were consistently decreased in PD in five countries. Increased mucin-layer-degrading genus Akkermansia possibly accounts for the development of RBD, and an additional decrease of SCFA-producing genera is likely to be associated with the transition from RBD to PD.ImportanceNineteen studies have been reported on gut microbiota in PD, whereas only one study has been reported in RBD from Germany. RBD has the highest likelihood ratio to develop PD. Our meta-analysis of RBD in Japan and Germany revealed increased mucin-layer-degrading genus Akkermansia in RBD. Genus Akkermansia may increase the intestinal permeability, as we previously observed in PD patients, and make the intestinal neural plexus exposed to oxidative stress, which can lead to abnormal aggregation of prion-like α-synuclein fibrils in the intestine. In contrast to PD, SCFA-producing bacteria were not decreased in RBD. As SCFA induces Treg cells, a decrease of SCFA-producing bacteria may be a prerequisite for the development of PD. We propose that prebiotic and/or probiotic therapeutic strategies to increase the intestinal mucin layer and to increase intestinal SCFA potentially retard the development of RBD and PD.

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Short-Chain Fatty Acid-Producing Gut Microbiota Is Decreased in Parkinson’s Disease but Not in Rapid-Eye-Movement Sleep Behavior Disorder

mSystems ◽

10.1128/msystems.00797-20 ◽

2020 ◽

Vol 5 (6) ◽

Author(s):

Hiroshi Nishiwaki ◽

Tomonari Hamaguchi ◽

Mikako Ito ◽

Tomohiro Ishida ◽

Tetsuya Maeda ◽

...

Keyword(s):

Fatty Acid ◽

Gut Microbiota ◽

Short Chain Fatty Acid ◽

Behavior Disorder ◽

Chain Fatty Acid ◽

Short Chain ◽

Rapid Eye Movement Sleep ◽

Data Set ◽

Sleep Behavior ◽

Mucin Layer

ABSTRACT Gut dysbiosis has been repeatedly reported in Parkinson’s disease (PD) but only once in idiopathic rapid-eye-movement sleep behavior disorder (iRBD) from Germany. Abnormal aggregation of α-synuclein fibrils causing PD possibly starts from the intestine, although this is still currently under debate. iRBD patients frequently develop PD. Early-stage gut dysbiosis that is causally associated with PD is thus expected to be observed in iRBD. We analyzed gut microbiota in 26 iRBD patients and 137 controls by 16S rRNA sequencing (16S rRNA-seq). Our iRBD data set was meta-analyzed with the German iRBD data set and was compared with gut microbiota in 223 PD patients. Unsupervised clustering of gut microbiota by LIGER, a topic model-based tool for single-cell RNA sequencing (RNA-seq) analysis, revealed four enterotypes in controls, iRBD, and PD. Short-chain fatty acid (SCFA)-producing bacteria were conserved in an enterotype observed in controls and iRBD, whereas they were less conserved in enterotypes observed in PD. Genus Akkermansia and family Akkermansiaceae were consistently increased in both iRBD in two countries and PD in five countries. Short-chain fatty acid (SCFA)-producing bacteria were not significantly decreased in iRBD in two countries. In contrast, we previously reported that recognized or putative SCFA-producing genera Faecalibacterium, Roseburia, and Lachnospiraceae ND3007 group were consistently decreased in PD in five countries. In α-synucleinopathy, increase of mucin-layer-degrading genus Akkermansia is observed at the stage of iRBD, whereas decrease of SCFA-producing genera becomes obvious with development of PD. IMPORTANCE Twenty studies on gut microbiota in PD have been reported, whereas only one study has been reported on iRBD from Germany. iRBD has the highest likelihood ratio to develop PD. Our meta-analysis of iRBD in Japan and Germany revealed increased mucin-layer-degrading genus Akkermansia in iRBD. Genus Akkermansia may increase the intestinal permeability, as we previously observed in PD patients, and may make the intestinal neural plexus exposed to oxidative stress, which can lead to abnormal aggregation of prion-like α-synuclein fibrils in the intestine. In contrast to PD, SCFA-producing bacteria were not decreased in iRBD. As SCFA induces regulatory T (Treg) cells, a decrease of SCFA-producing bacteria may be a prerequisite for the development of PD. We propose that prebiotic and/or probiotic therapeutic strategies to increase the intestinal mucin layer and to increase intestinal SCFA potentially retard the development of iRBD and PD.

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Neuropsychiatric Ramifications of COVID-19: Short-Chain Fatty Acid Deficiency and Disturbance of Microbiota-Gut-Brain Axis Signaling

BioMed Research International ◽

10.1155/2021/7880448 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Elizabeth M. Sajdel-Sulkowska

Keyword(s):

Fatty Acid ◽

Gut Microbiota ◽

Short Chain Fatty Acid ◽

Neuropsychiatric Disorders ◽

Chain Fatty Acid ◽

Brain Inflammation ◽

Short Chain ◽

Fecal Matter ◽

Gut Dysbiosis ◽

Anti Inflammatory

COVID-19-associated neuropsychiatric complications are soaring. There is an urgent need to understand the link between COVID-19 and neuropsychiatric disorders. To that end, this article addresses the premise that SARS-CoV-2 infection results in gut dysbiosis and an altered microbiota-gut-brain (MGB) axis that in turn contributes to the neuropsychiatric ramifications of COVID-19. Altered MGB axis activity has been implicated independently as a risk of neuropsychiatric disorders. A review of the changes in gut microbiota composition in individual psychiatric and neurological disorders and gut microbiota in COVID-19 patients revealed a shared “microbial signature” characterized by a lower microbial diversity and richness and a decrease in health-promoting anti-inflammatory commensal bacteria accompanied by an increase in opportunistic proinflammatory pathogens. Notably, there was a decrease in short-chain fatty acid (SCFA) producing bacteria. SCFAs are key bioactive microbial metabolites with anti-inflammatory functions and have been recognized as a critical signaling pathway in the MGB axis. SCFA deficiency is associated with brain inflammation, considered a cardinal feature of neuropsychiatric disorders. The link between SARS-CoV-2 infection, gut dysbiosis, and altered MGB axis is further supported by COVID-19-associated gastrointestinal symptoms, a high number of SARS-CoV-2 receptors, angiotensin-cleaving enzyme-2 (ACE-2) in the gut, and viral presence in the fecal matter. The binding of SARS-CoV-2 to the receptor results in ACE-2 deficiency that leads to decreased transport of vital dietary components, gut dysbiosis, proinflammatory gut status, increased permeability of the gut-blood barrier (GBB), and systemic inflammation. More clinical research is needed to substantiate further the linkages described above and evaluate the potential significance of gut microbiota as a diagnostic tool. Meanwhile, it is prudent to propose changes in dietary recommendations in favor of a high fiber diet or supplementation with SCFAs or probiotics to prevent or alleviate the neuropsychiatric ramifications of COVID-19.

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A combined administration of ampicillin and vancomycin induces mild colitis with decreased diversity of gut microbiota and perturbation of glutamine and short chain fatty acid metabolisms.

10.26226/morressier.59a6b343d462b80290b5437a ◽

2017 ◽

Author(s):

Akira Sonoda

Keyword(s):

Fatty Acid ◽

Gut Microbiota ◽

Short Chain Fatty Acid ◽

Chain Fatty Acid ◽

Short Chain ◽

Combined Administration

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Both living and dead Faecalibacterium prausnitzii alleviate HDM ‐induced allergic asthma through the modulation of gut microbiota and short‐chain fatty acid ( SCFAs ) production

Journal of the Science of Food and Agriculture ◽

10.1002/jsfa.11207 ◽

2021 ◽

Author(s):

Wenbing Hu ◽

Wenwei Lu ◽

Lingzhi Li ◽

Hao Zhang ◽

Yuan‐kun Lee ◽

...

Keyword(s):

Fatty Acid ◽

Gut Microbiota ◽

Allergic Asthma ◽

Short Chain Fatty Acid ◽

Chain Fatty Acid ◽

Short Chain ◽

Faecalibacterium Prausnitzii

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The use of disinfectant in barn cleaning alters microbial composition and increases carriage of Campylobacter jejuni in broiler chickens

10.1101/2021.10.29.466552 ◽

2021 ◽

Author(s):

Yi Fan ◽

Andrew Forgie ◽

Tingting Ju ◽

Camila Marcolla ◽

Tom Inglis ◽

...

Keyword(s):

Fatty Acid ◽

Gut Microbiota ◽

Campylobacter Jejuni ◽

Broiler Chicken ◽

Short Chain Fatty Acid ◽

Chain Fatty Acid ◽

Short Chain ◽

Microbial Composition ◽

Commercial Chicken ◽

Cecal Microbiota

To maintain food safety and flock health in broiler chicken production, biosecurity approaches to keep chicken barns free of pathogens are important. Canadian broiler chicken producers must deep clean their barns with chemical disinfectants at least once annually (full disinfection; FD) and may wash with water (water-wash; WW) throughout the year. However, many producers use FD after each flock, assuming a greater efficacy of more stringent cleaning protocols, although little information is known regarding how these two cleaning practices affect pathogen population and gut microbiota. In the current study, a cross-over experiment over four production cycles was conducted in seven commercial chicken barns to compare WW and FD. We evaluated the effects of barn cleaning method on the commercial broiler performance, cecal microbiota composition, pathogen occurrence and abundance, as well as short-chain fatty acid concentrations in the month-old broiler gut. The 30-day body weight and mortality rate were not affected by the barn cleaning methods. The WW resulted in a modest but significant effect on the structure of broiler cecal microbiota (weighted-UniFrac; adonis p = 0.05, and unweighted-UniFrac; adonis p = 0.01), with notable reductions in Campylobacter jejuni occurrence and abundance. In addition, the WW group had increased cecal acetate, butyrate and total short-chain fatty acid concentrations, which were negatively correlated with C. jejuni abundance. Our results support the use of WW over FD to enhance the activity of the gut microbiota and potentially reduce zoonotic transmission of C. jejuni in broiler production without previous disease challenges.

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