Alterations of the gut ecological and functional microenvironment in different stages of multiple sclerosis

Takewaki, Daiki; Suda, Wataru; Sato, Wakiro; Takayasu, Lena; Kumar, Naveen; Kimura, Kimitoshi; Kaga, Naoko; Mizuno, Toshiki; Miyake, Sachiko; Hattori, Masahira; Yamamura, Takashi

doi:10.1073/pnas.2011703117

Cited by 108 publications

(73 citation statements)

References 58 publications

(87 reference statements)

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“…These studies revealed differences in the relative abundance of rare phyla in primary progressive MS patients compared to healthy controls [35]. Secondary progressive MS patients show a relative increase of the Streptococcuss genus, which was suggested to correlate with increased oxidative stress in the gut [36]. In contrast, the gut microbiota of relapsing remitting MS patients was characterized by decreased abundance of short‐chain fatty acid (SCFA) producing bacteria compared to healthy controls [36], confirming previous studies that demonstrated a relative contribution of microbial SCFAs during neuroinflammation [37].…”

Section: Relevance Of Microbial Changes In Msmentioning

confidence: 99%

“…Secondary progressive MS patients show a relative increase of the Streptococcuss genus, which was suggested to correlate with increased oxidative stress in the gut [36]. In contrast, the gut microbiota of relapsing remitting MS patients was characterized by decreased abundance of short‐chain fatty acid (SCFA) producing bacteria compared to healthy controls [36], confirming previous studies that demonstrated a relative contribution of microbial SCFAs during neuroinflammation [37]. Potential mechanisms of gut microbiota alterations in MS patients have been studied in the EAE model that might in part be transferred back to the human disease.…”

Section: Relevance Of Microbial Changes In Msmentioning

confidence: 99%

“…So far, most of these studies were performed in patients with relapsing remitting MS. In contrast, researchers just started to investigate the importance of microbiota changes in patients with different stages of MS [35,36]. These studies revealed differences in the relative abundance of rare phyla in primary progressive MS patients compared to healthy controls [35].…”

Section: Relevance Of Microbial Changes In Msmentioning

confidence: 99%

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The role of the gut microbiota and microbial metabolites in neuroinflammation

et al. 2020

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Recent literature indicates a potential importance of the gut microbiota for immunemediated diseases. For instance, decreased diversity of commensals or an outgrowth of some bacterial strains, referred to as gut dysbiosis, was recently linked to hypertension, colitis, lupus, rheumatoid arthritis, and multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) as pivotal animal model of MS revealed a potential importance of microbial metabolites, including short-chain fatty acids or tryptophan metabolites. Both metabolites may influence the disease by modulation of the immune system, mainly by inducing Treg. These studies prompted researchers to investigate the contribution of the gut microbiota and microbial metabolites in the pathogenesis of MS. This review summarizes recent findings on the gut microbiota in MS patients and discusses the potential mechanisms how microbial metabolites may affect neuroinflammation. Many of these studies have been performed in the EAE model and were later reversely translated to humans. We also give a short summary on dietary high-salt effects on microbiota components and discuss the potential relevance of high-salt as a risk factor in MS.

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Section: Relevance Of Microbial Changes In Msmentioning

confidence: 99%

Section: Relevance Of Microbial Changes In Msmentioning

confidence: 99%

Section: Relevance Of Microbial Changes In Msmentioning

confidence: 99%

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The role of the gut microbiota and microbial metabolites in neuroinflammation

et al. 2020

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“…Examining downstream products of microbial metabolism might provide a species-independent assessment of the immune modulating activities of the gut microbiome. Recently, the composition of the gut microbiome was investigated alongside metabolomics, revealing decreased levels of the short-chain fatty acids (SCFAs) butyrate and propionate in the gut of MS patients 9 . In one study, the proportions of SCFA-producers Roseburia , Coprococcus and Blautia were reduced by between 2- and fivefold in patients with MS 10 .…”

Section: Introductionmentioning

confidence: 99%

Associations of serum short-chain fatty acids with circulating immune cells and serum biomarkers in patients with multiple sclerosis

Trend

Leffler

Jones

et al. 2021

Sci Rep

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Altered composition of gut bacteria and changes to the production of their bioactive metabolites, the short-chain fatty acids (SCFAs), have been implicated in the development of multiple sclerosis (MS). However, the immunomodulatory actions of SCFAs and intermediaries in their ability to influence MS pathogenesis are uncertain. In this study, levels of serum SCFAs were correlated with immune cell abundance and phenotype as well as with other relevant serum factors in blood samples taken at first presentation of Clinically Isolated Syndrome (CIS; an early form of MS) or MS and compared to healthy controls. There was a small but significant reduction in propionate levels in the serum of patients with CIS or MS compared with healthy controls. The frequencies of circulating T follicular regulatory cells and T follicular helper cells were significantly positively correlated with serum levels of propionate. Levels of butyrate associated positively with frequencies of IL-10-producing B-cells and negatively with frequencies of class-switched memory B-cells. TNF production by polyclonally-activated B-cells correlated negatively with acetate levels. Levels of serum SCFAs associated with changes in circulating immune cells and biomarkers implicated in the development of MS.

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“…To this point, the gut microbiome has been demonstrated in recent years to facilitate detection of disease [30][31][32][33][34]; classification of disease subtypes and progression stages [35][36][37]; prediction of clinical outcomes and treatment efficacy [38][39][40][41][42]; personalized nutrition by prediction of postprandial glycemic response [43][44][45];…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiome Predicts Clinically Important Improvement in Patients with Rheumatoid Arthritis

Gupta

Cunningham

Bakshi

et al. 2021

Preprint

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BackgroundRapid advances in the past decade have shown that dysbiosis of the gut microbiome is a key hallmark of rheumatoid arthritis (RA). Yet, the relationship between gut microbiome and clinical improvement in RA disease activity remains unclear. In this study, we explored the gut microbiome of patients with RA to identify features that are associated with, as well as predictive of, minimum clinically important improvement (MCII) in disease activity.MethodsWhole metagenome shotgun sequencing was performed on 64 stool samples, which were collected from 32 patients with RA at two separate time-points. The Clinical Disease Activity Index (CDAI) of each patient was measured at both time-points to assess achievement of MCII; depending on this clinical status, patients were distinguished into two groups. Multiple linear regression models were used to identify microbial taxa and biochemical pathways associated with MCII while controlling for potentially confounding factors. Lastly, a deep-learning neural network was trained upon gut microbiome, clinical, and demographic data at baseline to classify patients according to MCII status, thereby enabling the prediction of whether a patient will achieve MCII at follow-up.ResultsWe determined that MCII status can explain a significant proportion of the overall compositional variance in the gut microbiome (R2 = 3.8%, P = 0.005, PERMANOVA). Additionally, by looking at patients’ baseline gut microbiome profiles, we observed significantly different microbiome traits between patients who eventually showed MCII and those who did not. Taxonomic features include alpha- and beta-diversity measures, as well as several microbial taxa, such as Coprococcus, Bilophila sp. 4_1_30, and Ruminococcus sp. Functional profiling identified thirteen biochemical pathways, most of which were involved in the biosynthesis of L-arginine and L-methionine, to be differentially abundant between the MCII patient groups. In addition to these observations at baseline, we found microbiome features that vary differently in fold-change (from baseline to follow-up) between the two patient groups. These results could suggest that, depending on the clinical course, gut microbiomes not only start at different ecological states, but also are on separate trajectories. Finally, the neural network proved to be highly effective in predicting which patient will achieve MCII (balanced accuracy = 90.0%), demonstrating potential clinical utility of gut microbiome profiles.ConclusionsOur findings confirm the presence of taxonomic and functional signatures of the gut microbiome associated with MCII in RA patients. Ultimately, the gut microbiome may aid in the development of non-invasive tools for predicting future prognosis in RA.Trial registrationN/A

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Alterations of the gut ecological and functional microenvironment in different stages of multiple sclerosis

Cited by 108 publications

References 58 publications

The role of the gut microbiota and microbial metabolites in neuroinflammation

The role of the gut microbiota and microbial metabolites in neuroinflammation

Associations of serum short-chain fatty acids with circulating immune cells and serum biomarkers in patients with multiple sclerosis

Gut Microbiome Predicts Clinically Important Improvement in Patients with Rheumatoid Arthritis

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