Biology subjects

Ito, M.

Publications and source records attributed to Ito, M..

At least 55 records · Page 3Linked to original sources

bioRxiv2023

FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in meiotic DNA replication and recombination

The formation of RAD51/DMC1 filaments on single-stranded (ss)DNAs essential for homology search and strand exchange in DNA double-strand break (DSB) repair is tightly regulated. FIGNL1 AAA+++ ATPase controls RAD51-mediated recombination in human cells. However, its role in gametogenesis remains unsolved. Here, we characterized a germ-line-specific conditional knockout (cKO) mouse of FIGNL1. Fignl1 cKO male mice showed defective chromosome synapsis and impaired meiotic DSB repair with the accumulation of RAD51/DMC1 on meiotic chromosomes, supporting a positive role of FIGNL1 in homologous recombination at a post-assembly stage of RAD51/DMC1 filaments. Fignl1 cKO spermatocytes also accumulate RAD51/DMC1 on chromosomes in pre-meiotic S-phase. These RAD51/DMC1 assemblies are independent of meiotic DSB formation. We also showed that purified FIGNL1 dismantles RAD51 filament on double-stranded (ds)DNA as well as ssDNA. These results suggest an additional role of FIGNL1 in limiting the non-productive assembly of RAD51/DMC1 on native dsDNAs during pre-meiotic S-phase and meiotic prophase I.

molecular biology↗

bioRxiv2022

The canonical E2Fs together with RETINOBLASTOMA-RELATED are required to establish quiescence during plant development

Maintaining stable and transient quiescence in differentiated and stem cells, respectively, requires repression of the cell cycle. The plant RETINOBLASTOMA-RELATED (RBR) has been implicated in stem cell maintenance, presumably by forming repressor complexes with E2F transcription factors. Surprisingly we find that mutations in all three canonical E2Fs do not compromise the cell cycle, but similarly to RBR silencing, result in overproliferation. Contrary to the growth arrest upon RBR silencing, when exit from proliferation to differentiation is inhibited, the e2fabc mutant develops enlarged organs with supernumerary stem and differentiated cells as the quiescence is compromised. While E2F, RBR and the M-phase regulatory MYB3Rs are part of the DREAM repressor complexes, and recruited to overlapping groups of targets, they regulate distinct sets of genes. Only the loss of E2Fs but not the MYB3Rs interferes with quiescence, which might be due to the ability of E2Fs to control both G1-S and some key G2-M targets. We conclude that collectively the three canonical E2Fs in complex with RBR have central roles in establishing cellular quiescence during organ development, leading to enhanced plant growth.

plant biology↗

bioRxiv2022

Inositol pyrophosphate profiling reveals regulatory roles of IP6K2-dependent enhanced IP7 metabolism in enteric nervous system

Inositol pyrophosphates (PP-IPs) regulate diverse physiological processes; to better understand their functional roles, assessing their tissue-specific distribution is important. Here, we profiled PP-IP levels in mammalian organs using a novel HILIC-MS/MS protocol and discovered that the gastrointestinal tract (GIT) contained the highest levels of IP7 and its precursor IP6. Although their absolute levels in the GIT is diet-dependent, elevated IP7 metabolism still exists under dietary regimes devoid of exogenous IP7. Of the major GIT cells, enteric neurons selectively express the IP7-synthesizing enzyme IP6K2. IP6K2-knockout mice exhibited significantly impaired IP7 metabolism in the various organs including the proximal GIT. Additionally, HILIC-MS/MS analysis displayed that genetic ablation of IP6K2 significantly impaired IP7 metabolism in the gut and duodenal muscularis externa containing myenteric plexus. Whole transcriptome analysis of duodenal muscularis externa further suggested that IP6K2 inhibition induced the gene sets associated with mature neurons such as inhibitory, GABAergic and dopaminergic neurons, concomitantly with suppression of those for neural progenitor/stem cells and glial cells. In addition, IP6K2 inhibition explicitly affected transcript levels of certain genes modulating neuronal differentiation and functioning, implying critical roles of IP6K2-IP7 axis in developmental and functional regulation of enteric nervous system. These results collectively reveal an unexpected role of mammalian IP7--a highly active IP6K2-IP7 pathway is conducive to enteric nervous system.

molecular biology↗

bioRxiv2022

Neuronal representation of a working memory-based decision strategy in the motor and prefrontal cortico-basal ganglia loops

While animal and human decision strategies are typically explained by model-free and model-based reinforcement learning, their choice sequences often follow simple procedures based on working memory of past actions and rewards. Here we address how working memory-based choice strategies, such as win-stay-lose-switch (WSLS), are represented in the prefrontal and motor cortico-basal ganglia loops by simultaneous recording of neuronal activities in the dorsomedial striatum (DMS), the dorsolateral striatum (DLS), the medial prefrontal cortex (mPFC), and the primary motor cortex (M1). In order to compare neuronal representations when rats employ working memory-based strategies, we developed a new task paradigm, a continuous/intermittent choice task, consisting of choice and no-choice trials. While the continuous condition (CC) consisted of only choice trials, in the intermittent condition (IC), a no-choice trial was inserted after each choice trial to disrupt working memory of the previous choice and reward. Behaviors in CC showed high proportions of win-stay and lose-switch choices, which could be regarded as "a noisy WSLS strategy." Poisson regression of neural spikes revealed encoding specifically in CC of the previous action and reward before action choice and prospective coding of WSLS action during action execution. A striking finding was that the DLS and M1 in the motor cortico-basal ganglia loop carry substantial WM information about previous choices, rewards, and their interactions, in addition to current action coding. Significance StatementWorking memory-based decision strategies, such as win-stay-lose-switch (WSLS), are widely observed in humans and animals. To address neuronal bases of these strategies, we recorded neuronal activities of rat prefrontal and motor cortico-basal ganglia loops during continuous/intermittent choice tasks. The rat choice strategy was a noisy WSLS in the continuous choice condition, whereas non-WSLS was selected in the intermittent choice condition. In the continuous choice condition, the primary motor cortex and the dorsolateral striatum in the motor loop more strongly conveyed information about previous choices, rewards, and their interactions than the medial prefrontal cortex and the dorsomedial striatum in the prefrontal loop. These results demonstrate that the motor cortico-basal ganglia loop contributes to working memory-based decision strategies.

neuroscience↗

bioRxiv2022

Can SARS-CoV-2 transmit from a dead body?

Although it has been 2.5 years since the COVID-19 pandemic began, the transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a dead infected body remains unclear, and often, in Japan bereaved family members are not allowed to view in-person a loved one who has died from COVID-19. In this study, we analyzed the possibility of SARS-CoV-2 transmission from a dead body by using the hamster model. We also analyzed the effect of Angel-care--in which the pharynx, nostril, and rectum are plugged--and embalming on reducing transmissibility from dead bodies. We found that SARS-CoV-2 could be transmitted from the body of animals that died within a few days of infection; however, Angel-care and embalming were effective in preventing transmission from the dead body. These results suggest that protection from infection is essential when in contact with a SARS-CoV-2-infected dead body, and that sealing the cavities of a dead body is an important infection control step if embalming is not done. ImportanceWe found that SARS-CoV-2 could be transmitted from a dead body presumably via postmortem gases. However, we also found that postmortem care, such as plugging the pharynx, nostrils, and rectum, or embalming could prevent transmission from the dead body. These results indicate that protection from infection is essential when handling infected corpses, and that appropriate care of SARS-CoV-2-infected corpses is important.

microbiology↗

bioRxiv2022

Characterization of SARS-CoV-2 Omicron BA.2.75 clinical isolates

The prevalence of the Omicron subvariant BA.2.75 is rapidly increasing in India and Nepal. In addition, BA.2.75 has been detected in at least 34 other countries and is spreading globally. However, the virological features of BA.2.75 are largely unknown. Here, we evaluated the replicative ability and pathogenicity of BA.2.75 clinical isolates in Syrian hamsters. Although we found no substantial differences in weight change among hamsters infected with BA.2, BA.5, or BA.2.75, the replicative ability of BA.2.75 in the lungs was higher than that of BA.2 and BA.5. Of note, BA.2.75 caused focal viral pneumonia in hamsters, characterized by patchy inflammation interspersed in alveolar regions, which was not observed in BA.5-infected hamsters. Moreover, in competition assays, BA.2.75 replicated better than BA.5 in the lungs of hamsters. These results suggest that BA.2.75 can cause more severe respiratory disease than BA.5 and BA.2 and should be closely monitored.

microbiology↗

bioRxiv2022

Fc-modified SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models.

The use of therapeutic neutralizing antibodies against SARS-CoV-2 infection has been highly effective. However, there remain few practical antibodies against viruses that are acquiring mutations. In this study, we created 494 monoclonal antibodies from COVID-19-convalescent patients, and identified antibodies that exhibited comparable neutralizing ability to clinically used antibodies in the neutralization assay using pseudovirus and authentic virus including variants of concerns. These antibodies have different profiles against various mutations, which were confirmed by cell-based assay and cryo-electron microscopy. To prevent antibody-dependent enhancement, N297A modification was introduced, and showed a reduction of lung viral RNAs by therapeutic administration in a hamster model. In addition, an antibody cocktail consisting of three antibodies was also administered therapeutically to a macaque model, which resulted in reduced viral titers of swabs and lungs and reduced lung tissue damage scores. These results showed that our antibodies have sufficient antiviral activity as therapeutic candidates.

microbiology↗

bioRxiv2022

Targeted single-cell genomics reveals novel host adaptation strategies of the symbiotic bacteria Endozoicomonas in Acropora tenuis coral

Endozoicomonas bacteria symbiose with various marine organisms and are known to be beneficial for coral health. However, genome analysis of coral-associated Endozoicomonas has been limited owing to the difficulty in cultivation and metagenomic approach by contamination of host-derived sequences. In this study, we applied a novel single-cell genomics technique using droplet microfluidics to obtain single-cell amplified genome (SAGs) for coral-associated Endozoicomonas spp. genome. We obtained seven novel Endozoicomonas genomes from Acropora tenuis coral. These genomes revealed that Endozoicomonas bacteria played host-associated functions in host corals and had undergone independent host-adaptive evolution in different clades. These adaptive evolutions were mediated by host-derived eukaryotic-like genes, some of which were speculated to influence host immune mechanisms. These genes are speculated to enhance coral tolerance to environmental stresses. This study suggests the possibility of host adaptation of Endozoicomonas spp. in symbiosis with corals and their contribution to coral bleaching tolerance.

microbiology↗

bioRxiv2022

Avian H7N9 influenza viruses are evolutionarily constrained by stochastic processes during replication and transmission in mammals

H7N9 avian influenza viruses (AIV) have caused over 1,500 documented human infections since emerging in 2013. Although wild type H7N9 AIV can transmit by respiratory droplets in ferrets, they have not yet caused widespread outbreaks in humans. Previous studies have revealed molecular determinants of H7N9 AIV virus host-switching, but little is known about potential evolutionary constraints on this process. Here we compare patterns of sequence evolution for H7N9 AIV and mammalian H1N1 viruses during replication and transmission in ferrets. We show that three main factors - purifying selection, stochasticity, and very narrow transmission bottlenecks - combine to severely constrain the ability of H7N9 AIV to effectively adapt to mammalian hosts in isolated, acute spillover events. We find rare evidence of natural selection favoring new or mammalian-adapting mutations within ferrets, but no evidence of natural selection acting during transmission. We conclude that human-adapted H7N9 viruses are unlikely to emerge during typical spillover infections. Our findings are instead consistent with a model in which the emergence of a human-transmissible virus would be a rare and unpredictable, though highly consequential, "jackpot" event. Strategies to limit the total number of spillover infections will limit opportunities for the virus to win this evolutionary lottery.

microbiology↗

bioRxiv2022

Discrimination of SARS-CoV-2 Omicron sub-lineages BA.1 and BA.2 using a high-resolution melting-based assay: A pilot study

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. As of March 2022, Omicron variant BA.2 is rapidly replacing variant BA.1. As variant BA.2 may cause more severe disease than variant BA.1, variant BA.2 requires continuous monitoring. The current study aimed to develop a novel high-resolution melting (HRM) assay for variants BA.1 and BA.2 and to determine the sensitivity and specificity of our method using clinical samples. Here, we focused on the mutational spectra at three regions in the spike receptor-binding domain (RBD; R408, G446/L452, and S477/T478) for the variant-selective HRM analysis. Each variant was identified based on the mutational spectra as follows: no mutations (Alpha variant); L452R and T478K (Delta variant); G446S and S477N/T478K (Omicron variant BA.1); and R408S and S477N/T478K (Omicron variant BA.2). Upon analysis of mutation-coding RNA fragments, the melting peaks of the wild-type fragments were distinct from those of the mutant fragments. The sensitivity and specificity of this method were determined as 100% and more than 97.5%, respectively, based on 128 clinical samples (40 Alpha, 40 Delta, 40 Omicron variants BA.1/BA.1.1, and 8 Omicron BA.2). These results suggest that this HRM-based assay is a promising screening method for monitoring the transmission of Omicron variants BA.1 and BA.2.

microbiology↗

bioRxiv2022

The high-throughput perturbation of long non-coding RNA reveals functional features in stem cells and across cell-types

Within the scope of FANTOM6 consortium, we perform a large-scale knockdown of 200 long non-coding RNAs (lncRNAs) in human induced pluripotent stem (iPS) cells, and systematically characterize their roles in self-renewal and pluripotency. We find 36 lncRNAs (18%) exhibiting cell growth inhibition From the knockdown of 123 lncRNAs with transcriptome profiling, 36 lncRNAs (29.3%) show molecular phenotypes. Integrating the molecular phenotypes with chromatin-interaction assays further reveals cis- and trans-interacting partners as potential primary targets. Additionally, cell type enrichment analysis identifies lncRNAs associated with pluripotency while the knockdown of LINC02595, CATG00000090305.1 and RP11-148B6.2 modulates colony formation of iPS cells. We compare our results with previously published fibroblasts phenotyping data and find that 2.9% of the lncRNAs exhibit consistent cell growth phenotype, whereas we observe 58.3% agreement in molecular phenotypes. This highlights molecular phenotyping is more comprehensive in revealing affected pathways.

genomics↗

bioRxiv2021

Multi-omics analysis reveals cross-organism interactions in coral holobiont

Corals create an ecosystem, called a holobiont, with intracellular algae (zooxanthellae) and resident bacteria. Zooxanthellae and some bacteria play major roles in the physiological properties of the coral host. However, because of the difficulties in experimental verification of cross-organism interactions, the mechanisms underpinning these interactions are largely unknown. To address this, we here generated and then analyzed multi-omics datasets for corals, zooxanthellae, and bacteria collected at Okinawa, Japan, from November 2014 to September 2016. Using cross-organism co-expression analysis, we successfully characterized the host-alga relationship in the coral holobiont. Specifically, we observed that the coral host dominates the zooxanthellae. The multi-omics analysis also suggested that infection with coral-associated bacteria Endozoicomonas likely involves coral-like ephrin ligands, triggering an immune response of the coral host. This study highlights the potential of the multi-omics approach to elucidate coral-microbe interactions.

systems biology↗

bioRxiv2021

A hierarchical transcriptional network activates specific CDK inhibitors that regulate G2 to control cell size and number in Arabidopsis

How cell size and number are determined during organ development remains a fundamental question in cell biology. Here, we identified a GRAS family transcription factor, called SCARECROW-LIKE28 (SCL28), with a critical role in determining cell size in Arabidopsis. SCL28 is part of a transcriptional regulatory network downstream of the central MYB3Rs that regulate G2 to M phase cell cycle transition. We show that SCL28 forms a dimer with the AP2-type transcription factor, AtSMOS1, which defines the specificity for promoter binding and directly activates transcription of a specific set of SIAMESE-RELATED (SMR) family genes, encoding plant-specific inhibitors of cyclin-dependent kinases and thus inhibiting cell cycle progression at G2 and promoting the onset of endoreplication. Through this dose-dependent regulation of SMR transcription, SCL28 quantitatively sets the balance between cell size and number without dramatically changing final organ size. We propose that this hierarchical transcriptional network constitutes a cell cycle regulatory mechanism that allows to adjust cell size and number to attain robust organ growth.

plant biology↗

bioRxiv2021

Coordination chemogenetics for activation of GPCR-type glutamate receptors in brain tissue

Direct activation of cell-surface receptors is highly desirable for elucidating the physiological roles of receptors. However, subtype-selective ligands are very limited because of the high homology among receptor subtypes. A potential approach for selective activation of a receptor subtype is chemogenetics, in which both point mutagenesis of the receptors and designed ligands are used. However, ligand-binding properties are affected in most current methods. Here, we developed a chemogenetic method for direct activation of metabotropic glutamate receptor 1 (mGlu1), which plays essential roles in cerebellar functions in the brain. Our screening identified a mGlu1 mutant, mGlu1(N264H), that was directly activated by palladium complexes. Notably, a palladium complex showing low cytotoxicity successfully activated mGlu1 in mGlu1(N264H) knock-in mice, revealing that activation of endogenous mGlu1 is sufficient to evoke the critical cellular mechanism of synaptic plasticity, a basis of motor learning in the cerebellum.

neuroscience↗

bioRxiv2021

Highly-Neutralizing COVID-19-Convalescent-Plasmas Potently Block SARS-CoV-2 Replication and Pneumonia in Syrian Hamsters.

Despite various attempts to treat SARS-CoV-2-infected patients with COVID-19-convalescent plasmas, neither appropriate approach nor clinical utility has been established. We examined the efficacy of administration of highly-neutralizing COVID-19-convalescent plasma (hn-plasmas) and such plasma-derived IgG administration using the Syrian hamster COVID-19 model. Two hn-plasmas, which were in the best 1% of 340 neutralizing-activity-determined convalescent plasma samples, were intraperitoneally administered to SARS-CoV-2-infected hamsters, resulting in significant reduction of viral titers in lungs by up to 32-fold as compared to the viral titers in hamsters receiving control non-neutralizing plasma, while with two moderately neutralizing plasmas (mn-plasmas) administered, viral titer reduction was by up to 6-fold. IgG fractions purified from the two hn-plasmas also reduced viral titers in lungs than those from the two mn-plasmas. The severity of lung lesions seen in hamsters receiving hn-plasmas was minimal to moderate as assessed using micro-computerized tomography, which histological examination confirmed. Western blotting revealed that all four COVID-19-convalescent-plasmas variably contained antibodies against SARS-CoV-2 components including the receptor-binding domain and S1 domain. The present data strongly suggest that administering potent-neutralizing-activity-confirmed COVID-19-convalescent plasmas would be efficacious in treating patients with COVID-19. ImportanceConvalescent plasmas obtained from patients, who recovered from a specific infection, have been used as agents to treat other patients infected with the very pathogen. To treat using convalescent plasmas, despite that more than 10 randomized-controlled-clinical-trials have been conducted and more than 100 studies are currently ongoing, the effects of convalescent plasma against COVID-19 remained uncertain. On the other hand, certain COVID-19 vaccines have been shown to reduce the clinical COVID-19 onset by 94-95%, for which the elicited SARS-CoV-2-neutralizing antibodies are apparently directly responsible. Here, we demonstrate that highly-neutralizing-effect-confirmed convalescent plasmas significantly reduce the viral titers in the lung of SARS-CoV-2-infected Syrian hamsters and block the development of virally-induced lung lesions. The present data provide a proof-of-concept that the presence of highly-neutralizing antibody in COVID-19-convalescent plasmas is directly responsible for the reduction of viral replication and support the use of highly-neutralizing antibody-containing plasmas in COVID-19 therapy with convalescent plasmas.

microbiology↗

bioRxiv2021

Ultra-small cells and DPANN genome unveiled inside an extinct vent chimney

Chemosynthetic organisms flourish around deep-sea hydrothermal vents where energy-rich fluids are emitted from metal sulfide chimneys. In contrast to actively venting chimneys, the nature of microbial life in extinct chimneys without fluid venting remains largely unknown. Here, the occurrence of ultra-small cells in silica-filled grain boundaries inside an extinct chimney is demonstrated by high-resolution bio-signature mapping. The ultra-small cells are associated with extracellularly precipitated Cu2O nanocrystals. Single-gene analysis shows that the chimney interior is dominated by a member of Pacearchaeota known as a major phylum of DPANN. Genome-resolved metagenomic analysis reveals that the chimney Pacearchaeota member is equipped with a nearly full set of genes for fermentation-based energy generation from nucleic acids, in contrast to previously characterized Pacearchaeota members lacking many genes for nucleic acid fermentation. We infer that the ultra-small cells associated with silica and extracellular Cu2O nanocrystals in the grain boundaries are Pacearchaeota, on the basis of the experimentally demonstrated capability of silica to concentrate nucleic acids from seawater and the presence of Cu-exporting genes in a reconstructed Pacearchaeota genome. Given the existence of ~3-billion-year-old submarine hydrothermally deposited silica, proliferation of microbial life using silica-bound nucleic acids might be relevant to the primitive vent biosphere.

microbiology↗

bioRxiv2021

Optimization of an LNP-mRNA vaccine candidate targeting SARS-CoV-2 receptor-binding domain

In 2020, two mRNA-based vaccines, encoding the full length of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, have been introduced for control of the coronavirus disease (COVID-19) pandemic1,2. However, reactogenicity, such as fever, caused by innate immune responses to the vaccine formulation remains to be improved. Here, we optimized a lipid nanoparticle (LNP)-based mRNA vaccine candidate, encoding the SARS-CoV-2 spike protein receptor-binding domain (LNP-mRNA-RBD), which showed improved immunogenicity by removing reactogenic materials from the vaccine formulation and protective potential against SARS-CoV-2 infection in cynomolgus macaques. LNP-mRNA-RBD induced robust antigen-specific B cells and follicular helper T cells in the BALB/c strain but not in the C57BL/6 strain; the two strains have contrasting abilities to induce type I interferon production by dendritic cells. Removal of reactogenic materials from original synthesized mRNA by HPLC reduced type I interferon (IFN) production by dendritic cells, which improved immunogenicity. Immunization of cynomolgus macaques with an LNP encapsulating HPLC-purified mRNA induced robust anti-RBD IgG in the plasma and in various mucosal areas, including airways, thereby conferring protection against SARS-CoV-2 infection. Therefore, fine-tuning the balance between the immunogenic and reactogenic activity of mRNA-based vaccine formulations may offer safer and more efficacious outcomes.

immunology↗

bioRxiv2020

Rapid-Eye-Movement Sleep Behavior Disorder Exhibits Similar but Distinct Gut Dysbiosis Compared to Parkinson's Disease

Gut dysbiosis has been reported repeatedly in Parkinsons disease (PD), but once in rapid-eye-movement sleep behavior disorder (RBD) from Germany. Abnormal aggregation of -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 -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.

microbiology↗