Gut microbiome of multiple sclerosis patients and paired household healthy controls reveal associations with disease risk and course

Zhou, Xiaoyuan; Baumann, Ryan; Gao, Xiaohui; Mendoza, Myra; Singh, Sneha; Sand, Ilana Katz; Xia, Zongqi; Cox, Laura M.; Chitnis, Tanuja; Yoon, Hongsup; Moles, Laura; Caillier, Stacy J.; Santaniello, Adam; Ackermann, Gail; Harroud, Adil; Lincoln, Robin; Gomez, Refujia; Peña, Antonio González; Digga, Elise; Hakim, Daniel; Vázquez-Baeza, Yoshiki; Soman, Karthik; Warto, Shannon; Humphrey, Greg; Farez, Mauricio; Gerdes, Lisa Ann; Oksenberg, Jorge R.; Zamvil, Scott S.; Chandran, Siddharthan; Connick, Peter; Otaegui, David; Castillo-Triviño, Tamara; Hauser, Stephen L.; Gelfand, Jeffrey M.; Weiner, Howard L.; Hohlfeld, Reinhard; Wekerle, Hartmut; Graves, Jennifer; Bar‐Or, Amit; Cree, Bruce A.C.; Correale, Jorge; Knight, Rob; Baranzini, Sergio E.

doi:10.1016/j.cell.2022.08.021

Cited by 144 publications

(106 citation statements)

References 142 publications

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“…Enrichment of E. lenta is associated with various inflammatory states, including colitis 56 and multiple sclerosis 57 . The role of Blautia in disease is more controversial, as both depletion and enrichment of this genus has been associated with inflammatory states (e.g.—depletion of Blautia in patients with Crohn’s disease 58 , colorectal cancer 59 , and multiple sclerosis 60 ; enrichment of Blautia in patients with multiple sclerosis 48 and inflammatory bowel syndrome 61 ).…”

Section: Discussionmentioning

confidence: 99%

Breast cancer patients from the Midwest region of the United States have reduced levels of short-chain fatty acid-producing gut bacteria

Shrode

Knobbe

Cady

et al. 2023

Sci Rep

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As geographical location can impact the gut microbiome, it is important to study region-specific microbiome signatures of various diseases. Therefore, we profiled the gut microbiome of breast cancer (BC) patients of the Midwestern region of the United States. The bacterial component of the gut microbiome was profiled utilizing 16S ribosomal RNA sequencing. Additionally, a gene pathway analysis was performed to assess the functional capabilities of the bacterial microbiome. Alpha diversity was not significantly different between BC and healthy controls (HC), however beta diversity revealed distinct clustering between the two groups at the species and genera level. Wilcoxon Rank Sum test revealed modulation of several gut bacteria in BC specifically reduced abundance of those linked with beneficial effects such as Faecalibacterium prausnitzii. Machine learning analysis confirmed the significance of several of the modulated bacteria found by the univariate analysis. The functional analysis showed a decreased abundance of SCFA (propionate) production in BC compared to HC. In conclusion, we observed gut dysbiosis in BC with the depletion of SCFA-producing gut bacteria suggesting their role in the pathobiology of breast cancer. Mechanistic understanding of gut bacterial dysbiosis in breast cancer could lead to refined prevention and treatment.

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Section: Discussionmentioning

confidence: 99%

Breast cancer patients from the Midwest region of the United States have reduced levels of short-chain fatty acid-producing gut bacteria

Shrode

Knobbe

Cady

et al. 2023

Sci Rep

View full text Add to dashboard Cite

show abstract

“…As exemplified by the recent iMSMS Consortium study (Zhou et al, 2022), there are significant differences in the gut microbiome species and gut-derived metabolites in patients across MS disease states, countries of residence, and DMTs. Thus, in future humans studies, it will be important to ensure that studies are sufficiently powered, include both males and females, compare patients across disease states (RRMS vs. SPMS vs. CIS), and take into account patient age, latitude of residence, and treatment with DMTs.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, in future humans studies, it will be important to ensure that studies are sufficiently powered, include both males and females, compare patients across disease states (RRMS vs. SPMS vs. CIS), and take into account patient age, latitude of residence, and treatment with DMTs. Based on the iMSMS Consortium study results (Zhou et al, 2022), demonstrating that diet alone does not account for microbiota diversity, future MS microbiome studies will also need to account not only for patient dietary habits but also for other environmental exposures, such as water or air, that may influence the gut microbiome. In addition, consistency between sampled tissues will be critical, as there are known differences in gut bacterial and FA composition between serum and fecal samples.…”

Section: Discussionmentioning

confidence: 99%

Advantages and limitations of experimental autoimmune encephalomyelitis in breaking down the role of the gut microbiome in multiple sclerosis

Melamed

Palmer

Fonken

2022

Front. Mol. Neurosci.

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Since the first model of experimental autoimmune encephalomyelitis (EAE) was introduced almost a century ago, there has been an ongoing scientific debate about the risks and benefits of using EAE as a model of multiple sclerosis (MS). While there are notable limitations of translating EAE studies directly to human patients, EAE continues to be the most widely used model of MS, and EAE studies have contributed to multiple key breakthroughs in our understanding of MS pathogenesis and discovery of MS therapeutics. In addition, insights from EAE have led to a better understanding of modifiable environmental factors that can influence MS initiation and progression. In this review, we discuss how MS patient and EAE studies compare in our learning about the role of gut microbiome, diet, alcohol, probiotics, antibiotics, and fecal microbiome transplant in neuroinflammation. Ultimately, the combination of rigorous EAE animal studies, novel bioinformatic approaches, use of human cell lines, and implementation of well-powered, age- and sex-matched randomized controlled MS patient trials will be essential for improving MS patient outcomes and developing novel MS therapeutics to prevent and revert MS disease progression.

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“…Such reduced diversity also characterizes MS with specific absence of certain stains e.g., Clostridia subclusters and Bacteroides species (26-28). Obesity, an emerging risk factor for MS, also associates with altered gut microbiome (29,30).…”

Section: Pathogens and Cns Autoimmunitymentioning

confidence: 99%

Hypothesis of a potential BrainBiota and its relation to CNS autoimmune inflammation

et al. 2022

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Infectious agents have been long considered to play a role in the pathogenesis of neurological diseases as part of the interaction between genetic susceptibility and the environment. The role of bacteria in CNS autoimmunity has also been highlighted by changes in the diversity of gut microbiota in patients with neurological diseases such as Parkinson’s disease, Alzheimer disease and multiple sclerosis, emphasizing the role of the gut-brain axis. We discuss the hypothesis of a brain microbiota, the BrainBiota: bacteria living in symbiosis with brain cells. Existence of various bacteria in the human brain is suggested by morphological evidence, presence of bacterial proteins, metabolites, transcripts and mucosal-associated invariant T cells. Based on our data, we discuss the hypothesis that these bacteria are an integral part of brain development and immune tolerance as well as directly linked to the gut microbiome. We further suggest that changes of the BrainBiota during brain diseases may be the consequence or cause of the chronic inflammation similarly to the gut microbiota.

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Gut microbiome of multiple sclerosis patients and paired household healthy controls reveal associations with disease risk and course

Cited by 144 publications

References 142 publications

Breast cancer patients from the Midwest region of the United States have reduced levels of short-chain fatty acid-producing gut bacteria

Breast cancer patients from the Midwest region of the United States have reduced levels of short-chain fatty acid-producing gut bacteria

Advantages and limitations of experimental autoimmune encephalomyelitis in breaking down the role of the gut microbiome in multiple sclerosis

Hypothesis of a potential BrainBiota and its relation to CNS autoimmune inflammation

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