Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models

Cekanaviciute, Egle; Yoo, Byung Hoon; Runia, Tessel F.; Debelius, Justine W.; Singh, Sneha; Nelson, Charlotte; Kanner, Rachel; Bencosme, Yadira; Lee, Yun Kyung; Hauser, Stephen L.; Crabtree-Hartman, Elizabeth; Sand, Ilana Katz; Gacias, Mar; Zhu, Yunjiao; Casaccia, Patrizia; Cree, Bruce A.C.; Knight, Rob; Mazmanian, Sarkis K.; Baranzini, Sergio E.

doi:10.1073/pnas.1711235114

Cited by 782 publications

(835 citation statements)

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“…A critical contribution of the microbiota to autoimmune diseases was recently underpinned by the observation that transfer of MS patients microbiota into mice could modulate EAE. GF mice reconstituted with MS patient microbiota developed more severe EAE attributed to a diminished generation of IL‐10 producing Tregs compared with GF mice reconstituted with microbiota derived from healthy controls . A finding shared by another study using GF relapsing–remitting (RR) mice as recipients of MS patient microbiota.…”

Section: Introductionmentioning

confidence: 93%

The role of salt for immune cell function and disease

Willebrand

Kleinewietfeld

2018

Immunology

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The immune system evolved to protect organisms from invading pathogens. A network of pro- and anti-inflammatory cell types equipped with special effector molecules guarantees efficient elimination of intruders like viruses and bacteria. However, imbalances can lead to an excessive response of effector cells incurring autoimmune or allergic diseases. An interplay of genetic and environmental factors contributes to autoimmune diseases and recent studies provided evidence for an impact of dietary habits on the immune status and related disorders. Western societies underwent a change in lifestyle associated with changes in food consumption. Salt (sodium chloride) is one component prevalent in processed food frequently consumed in western countries. Here we summarize recent advances in understanding the mechanisms behind the effects of sodium chloride on immune cells like regulatory T cells (Tregs) and T helper (T ) 17 cells and its implication as a risk factor for several diseases.

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Section: Introductionmentioning

confidence: 93%

The role of salt for immune cell function and disease

Willebrand

Kleinewietfeld

2018

Immunology

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“…The results obtained in the studies of transplantation of fecal content of patients with MS to germ-free mice that suffer from a less severe form of EAE suggest that changes in the microbiota of individuals with MS could be functionally relevant by enhancing experimental disease. Pröbstel and Baranzini [20] review their own [22] and findings by Berer et al [23], providing evidence for the importance of alterations of the microbiota in the severity and progression of the disease. Fecal transplantations of MS samples were able to restore EAE susceptibility in 2 different models of germ-free mice.…”

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confidence: 99%

“…Are these changes relevant? Two recent studies evaluated whether the changes in the specific taxa observed in patients with MS had functional effects on disease [22,23]. The results obtained in the studies of transplantation of fecal content of patients with MS to germ-free mice that suffer from a less severe form of EAE suggest that changes in the microbiota of individuals with MS could be functionally relevant by enhancing experimental disease.…”

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confidence: 99%

The Microbiome and Neurologic Disease: Past and Future of a 2-Way Interaction

Ochoa‐Repáraz

Kasper

2018

Neurotherapeutics

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“…The mode of health-promoting mechanisms include the increase of mucus thickness and gut barrier function (Everard et al 2013), direct host immune stimulation (Ottman et al 2017b), and stimulation of a beneficial mucosal community (Chapter 4 and 5) . Nevertheless, the relative abundance of Akkermansia muciniphila has also been associated with negative health consequences such as Parkinson's disease (Heintz-Buschart et al 2018), Alzheimer's disease (Vogt et al 2017), multiple sclerosis (Cekanaviciute et al 2017) and colorectal cancer . These health associations are mainly demonstrated in mouse models, and often the design of the above-mentioned studies are not as robust as those that demonstrate beneficial effect.…”

Section: Novel Probiotic Strainsmentioning

confidence: 99%

Cross-feeding interactions of gut symbionts driven by human milk oligosaccharidesand mucins

Chia¹

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Chapter 4Microbial metabolic networks at the mucus layer lead to dietindependent butyrate and vitamin B12 production by intestinal symbionts 71 Chapter 5Deciphering trophic interaction between Akkermansia muciniphila and the butyrogenic gut commensal Anaerostipes caccae using a metatranscriptomic approach 97 Chapter 6General discussion 123 Chapter 7 Thesis summary & Nederlandse samenvatting 143 Appendices References 153Co-author affiliations 179Acknowledgements 183About the author 184List of publications 185 VLAG training activities 186Chapter 1 General introduction and thesis outlineChapter 1 2 General introductionHumans can be considered holobionts, consisting of cells from the host and an even larger number of microorganisms (Postler and Ghosh 2017). The majority of microbes are residing in the gut (Sender et al 2016). The human gut microbiota is a complex ecosystem consisting of bacteria, archaea, microeukaryotes and viruses (Clemente et al 2012). Over 2000 species-level phylotypes (prokaryotes including bacteria and archaea) have been detected for the gut microbiota, with each individual estimated to host at least 160 species (Qin et al 2010, Zoetendal et al 2008. The gut microbiota may impact the well-being of human and susceptibility for diseases by interacting with our metabolic, immune and neurological system (Honda and Littman 2016, Koh et al 2016, Rogers et al 2016. Furthermore, the gut microbiota contributes to a variety of metabolic functions and can be seen as an essential part of our digestive system (El Kaoutari et al 2013). Bacterial symbionts allow the human hosts to utilise inaccessible nutrients by converting complex substrates to short chain fatty acid (SCFA) and vitamins (Fisher et al 2017). Bacterial-derived SCFAs are estimated to contribute about 10% of our daily caloric requirement (Bergman 1990). While all SCFAs are vital for maintaining gut homeostasis, butyrate is of particular interest because it has been attributed to a range of health-promoting functions. Butyrate is the primary energy source for colonic epithelial cells and is associated with the enhancement of colonic barrier function, increase of satiety, pain relief, anti-inflammatory responses, and protection against colorectal cancer (Banasiewicz et al 2013, Bolognini et al 2016, Donohoe et al 2011, Furusawa et al 2013, Goncalves and Martel 2013.Considering the physiological benefits of butyrate to human health, this thesis investigates the microbial interaction of gut symbionts that support butyrate production driven primarily by the host produced glycans in human milk and mucus. Glycans are compounds consisting of an array of glycosidically linked monosaccharides (monosaccharides and disaccharides are collectively termed sugars) such as human milk oligosaccharides (HMOS) and mucins (Varki and Kornfeld 2017). HMOS present in mother milk are the major compositional and functional driver of the infant gut microbiota (Backhed et al 2015). Mucin glycans covering the intestinal lining create a stable niche for bacterial coloni...

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Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models

Cited by 782 publications

References 38 publications

The role of salt for immune cell function and disease

The role of salt for immune cell function and disease

The Microbiome and Neurologic Disease: Past and Future of a 2-Way Interaction

Cross-feeding interactions of gut symbionts driven by human milk oligosaccharidesand mucins

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