Alterations of the gut mycobiome in patients with MS

Shah, Saumya; Locca, Alberto; Dorsett, Yair; Cantoni, Claudia; Ghezzi, Laura; Lin, Qingqi; Bokoliya, Suresh; Panier, Hunter; Suther, Cassandra; Gormley, Matthew; Liu, Yue; Evans, Emily; Mikesell, Robert; Obert, Kathleen A.; Salter, Amber; Cross, Anne H.; Tarr, Phillip I.; Lovett-Racke, Amy E.; Piccio, Laura; Zhou, Yanjiao

doi:10.1016/j.ebiom.2021.103557

Cited by 43 publications

(42 citation statements)

References 58 publications

(64 reference statements)

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“…Previous mycobiome studies frequently reported that Saccharomyces was one of the most prevalent fungi in the human gut ( 18 , 37 , 39 , 43 , 44 ). Our present study also demonstrated that it was one of most abundant fungi in the participants’ gut, especially in the CKD patients.…”

Section: Discussionmentioning

confidence: 99%

Gut Mycobiome in Patients With Chronic Kidney Disease Was Altered and Associated With Immunological Profiles

Wei

et al. 2022

Front. Immunol.

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ObjectivesMounting evidence suggests that bacterial dysbiosis and immunity disorder are associated with patients with chronic kidney disease (CKD), but the mycobiome is beginning to gain recognition as a fundamental part of our microbiome. We aim to characterize the profile of the mycobiome in the gut of CKD patients and its correlation to serum immunological profiles.Methods and materialsNinety-two CKD patients and sex–age–body mass index (BMI)–matched healthy controls (HCs) were recruited. Fresh samples were collected using sterile containers. ITS transcribed spacer ribosomal RNA gene sequencing was performed on the samples. An immunoturbidimetric test was used to assess the serum levels of immunological features.ResultsThe CKD cohort displayed a different microbial community from that in the HC cohort according to principal coordinate analysis (PCoA). (P=0.001). The comparison of the two cohorts showed that the CKD cohort had significantly higher gut microbial richness and diversity (P<0.05). The CKD cohort had lower abundances of Candida, Bjerkandera, Rhodotorula, and Ganoderma compared to the HC cohort, while it had higher Saccharomyces (P<0.05). However, the microbial community alteration was inconsistent with the severity of kidney damage in patients, as only patients in CKD stage 1~3 had differed microbial community concerning for HCs based on PCoA (P<0.05). The serum concentration of the kappa light chain in CKD patients was positively associated with Saccharomyces, whereas the it was negatively associated with Ganoderma (P<0.05).ConclusionsNot only was gut mycobiome dysbiosis observed in CKD patients, but the dysbiosis was also associated with the immunological disorder. These findings suggest that therapeutic strategies targeting gut mycobiome might be effective.

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Section: Discussionmentioning

confidence: 99%

Gut Mycobiome in Patients With Chronic Kidney Disease Was Altered and Associated With Immunological Profiles

Wei

et al. 2022

Front. Immunol.

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“…In pwMS, specific bacterial taxa related to proinflammatory responses are favored ( 12 ) while short-chain fatty acid (SCFAs)-producing bacteria are reduced ( 11 ). Interestingly, researchers are also starting to link MS to a fungal etiology, having revealed the presence of mycotoxins, IL-17, chitotriosidase, and antibodies against fungi ( 13 , 14 ) in persons with MS (pwMS). Indirectly, alterations of intestinal permeability (IP) have also been detected in relapsing-remitting MS (RR-MS) patients ( 15 ), with zonulin being recognized as a peripheral marker of IP and blood–brain barrier (BBB) in MS ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Proinflammatory mucosal-associated invariant CD8+ T cells react to gut flora yeasts and infiltrate multiple sclerosis brain

et al. 2022

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The composition of the intestinal microbiota plays a critical role in shaping the immune system. Modern lifestyle, the inappropriate use of antibiotics, and exposure to pollution have significantly affected the composition of commensal microorganisms. The intestinal microbiota has been shown to sustain inappropriate autoimmune responses at distant sites in animal models of disease, and may also have a role in immune-mediated central nervous system (CNS) diseases such as multiple sclerosis (MS). We studied the composition of the gut mycobiota in fecal samples from 27 persons with MS (pwMS) and in 18 healthy donors (HD), including 5 pairs of homozygous twins discordant for MS. We found a tendency towards higher fungal abundance and richness in the MS group, and we observed that MS twins showed a higher rate of food-associated strains, such as Saccharomyces cerevisiae. We then found that in pwMS, a distinct population of cells with antibacterial and antifungal activity is expanded during the remitting phase and markedly decreases during clinically and/or radiologically active disease. These cells, named MAIT (mucosal-associated invariant T cells) lymphocytes, were significantly more activated in pwMS compared to HD in response to S. cerevisiae and Candida albicans strains isolated from fecal samples. This activation was also mediated by fungal-induced IL-23 secretion by innate immune cells. Finally, immunofluorescent stainings of MS post-mortem brain tissues from persons with the secondary progressive form of the disease showed that MAIT cells cross the blood–brain barrier (BBB) and produce pro-inflammatory cytokines in the brain. These results were in agreement with the hypothesis that dysbiosis of the gut microbiota might determine the inappropriate response of a subset of pathogenic mucosal T cells and favor the development of systemic inflammatory and autoimmune diseases.

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“…Alterations in the gut bacterial microbiota structure have been well studied in metabolic diseases such as gestational diabetes mellitus (GDM) ( Wu et al, 2021 ), type 2 diabetes ( Bielka et al, 2022 ) and obesity ( Turnbaugh et al, 2009 ), and an increasing number of reports suggest that gut commensal fungi, as an important component of the intestinal microbiome, also influence host metabolic homeostasis ( Shah et al, 2021 ; Zhang et al, 2021 ). Recent studies indicate that commensal fungi have the potential to influence host metabolism directly.…”

Section: Introductionmentioning

confidence: 99%

The Gut Mycobiome Characterization of Gestational Diabetes Mellitus and Its Association With Dietary Intervention

Mo²,

Mu³

et al. 2022

Front. Microbiol.

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Gestational diabetes mellitus (GDM) is a high-risk pregnancy complication that is associated with metabolic disorder phenotypes, such as abnormal blood glucose and obesity. The active interface between gut microbiota and diet contributes to metabolic homeostasis in GDM. However, the contributions of gut mycobiome have been neglected. Here, we profiled the gut fungi between GDM and healthy subjects at two time points and investigate whether variations in gut mycobiome correlate with key features of host metabolism and diet management in this observational study. We identified that Hanseniaspora, Torulaspora, Auricularia, Alternaria, and Candida contributed to GDM patient clustering, indicating that these fungal taxa are associated with abnormal blood glucose levels, and the causality needs to be further explored. While Penicillium, Ganoderma, Fusarium, Chaetomium, and Heterobasidion had significant explanatory effects on healthy subject clustering. In addition, spearman analysis further indicated that blood glucose levels were negatively correlated with polysaccharide-producing genera, Ganoderma, which could be reshaped by the short-term diet. The Penicillium which was negatively correlates with metabolic parameters, also exhibited the antimicrobial attribute by the fungal-bacterial interaction analysis. These data suggest that host metabolic homeostasis in GDM may be influenced by variability in the mycobiome and could be reshaped by the diet intervention. This work reveals the potential significance of the gut mycobiome in health and has implications for the beneficial effects of diet intervention on host metabolic homeostasis through regulating gut fungal abundance and metabolites.

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Alterations of the gut mycobiome in patients with MS

Cited by 43 publications

References 58 publications

Gut Mycobiome in Patients With Chronic Kidney Disease Was Altered and Associated With Immunological Profiles

Gut Mycobiome in Patients With Chronic Kidney Disease Was Altered and Associated With Immunological Profiles

Proinflammatory mucosal-associated invariant CD8+ T cells react to gut flora yeasts and infiltrate multiple sclerosis brain

The Gut Mycobiome Characterization of Gestational Diabetes Mellitus and Its Association With Dietary Intervention

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