Insights into microbiome research 5: Mapping is first but function must come next

Abstract

Several efforts identifying differential bacterial prevalence in the gut of multiple sclerosis (MS) patients have been reported and many more are underway. While these are critical first steps in determining the involvement of gut microbes in MS pathogenesis, functional assays (both in vitro and in vivo) are needed to explore the mechanisms underlying the observed changes and ultimately implementing interventional strategies to counter severity, progression or even reduce the chance that it develops in the first place.

Keywords

Multiple sclerosis microbiome mapping

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References

Ochoa-Reparaz

Kirby

Kasper

LH.

The gut microbiome and multiple sclerosis. Cold Spring Harb Perspect Med 2018; 8: a029017.

Pröbstel

Baranzini

. The role of the gut microbiome in multiple sclerosis risk and progression: Towards characterization of the “MS Microbiome.” Neurotherapeutics 2018; 15: 126–134.

Huang

Lee

Mazmanian

SK.

The human commensal Bacteroides fragilis binds intestinal mucin. Anaerobe 2011; 17: 137–141.

Kou

Chen

et al . A tolerant lactic acid bacteria, Lactobacillus paracasei, and its immunoregulatory function. Can J Microbiol 2014; 60: 729–736.

Laiño

Villena

Kanmani

et al . Immunoregulatory effects triggered by lactic acid bacteria exopolysaccharides: New insights into molecular interactions with host cells. Microorganisms 2016; 4: E27.

Ochoa-Repáraz

Mielcarz

Ditrio

et al . Central nervous system demyelinating disease protection by the human commensal Bacteroides fragilis depends on polysaccharide A expression. J Immunol 2010; 185: 4101–4108.

Telesford

Yan

Ochoa-Reparaz

et al . A commensal symbiotic factor derived from Bacteroides fragilis promotes human CD39(+)Foxp3(+) T cells and Treg function. Gut Microbes 2015; 6: 234–242.

Mirpuri

Sotnikov

Myers

et al . Lactobacillus rhamnosus (LGG) regulates IL-10 signaling in the developing murine colon through upregulation of the IL-10R2 receptor subunit. PLoS ONE 2012; 7: e51955.

Atarashi

Suda

Luo

et al . Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation. Science 2017; 358: 359–365.

10.

Kim

Hong

Park

et al . Immunization with Escherichia coli outer membrane vesicles protects bacteria-induced lethality via Th1 and Th17 cell responses. J Immunol 2013; 190: 4092–4102.

11.

Kopitar

Ihan Hren

Ihan

Commensal oral bacteria antigens prime human dendritic cells to induce Th1, Th2 or Treg differentiation. Oral Microbiol Immunol 2006; 21: 1–5.

12.

Lin

Tsai

et al . Heat-killed lactic acid bacteria enhance immunomodulatory potential by skewing the immune response toward Th1 polarization. J Food Sci 2011; 76: M260–127.

13.

Shiba

Kawakami

Sasaki

et al . Effects of intestinal bacteria-derived p-cresyl sulfate on Th1-type immune response in vivo and in vitro. Toxicol Appl Pharmacol 2014; 274: 191–199.

14.

Smith

Liu

Peng

et al . Comparison of a classical Th1 bacteria versus a Th17 bacteria as adjuvant in the induction of experimental autoimmune encephalomyelitis. J Neuroimmunol 2011; 237: 33–38.

15.

Smits

van Beelen

Hessle

et al . Commensal Gram-negative bacteria prime human dendritic cells for enhanced IL-23 and IL-27 expression and enhanced Th1 development. Eur J Immunol 2004; 34: 1371–1380.

16.

Fujiwara

Inoue

Wakabayashi

et al . The anti-allergic effects of lactic acid bacteria are strain dependent and mediated by effects on both Th1/Th2 cytokine expression and balance. Int Arch Allergy Immunol 2004; 135: 205–215.

17.

Cekanaviciute

Yoo

Runia

et al . Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci USA 2017; 114: 10713–10718.

18.

Duan

Chung

Troy

et al . Microbial colonization drives expansion of IL-1 receptor 1-expressing and IL-17-producing gamma/delta T cells. Cell Host Microbe 2010; 7: 140–150.

19.

Atarashi

Tanoue

Ando

et al . Th17 Cell induction by adhesion of microbes to intestinal epithelial cells. Cell 2015; 163: 367–380.

20.

Chiu

Ching

Wang

et al . Monocolonization of germ-free mice with Bacteroides fragilis protects against dextran sulfate sodium-induced acute colitis. Biomed Res Int 2014; 2014: 675786.

21.

Round

Mazmanian

SK.

Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci USA 2010; 107: 12204–12209.

22.

Hudcovic

Kozáková

Kolinská

et al . Monocolonization with Bacteroides ovatus protects immunodeficient SCID mice from mortality in chronic intestinal inflammation caused by long-lasting dextran sodium sulfate treatment. Physiol Res 2009; 58: 101–110.

23.

Rask

Evertsson

Telemo

et al . A full flora, but not monocolonization by Escherichia coli or lactobacilli, supports tolerogenic processing of a fed antigen. Scand J Immunol 2005; 61: 529–535.

24.

Bohn

Bechtold

Zahir

et al . Host gene expression in the colon of gnotobiotic interleukin-2-deficient mice colonized with commensal colitogenic or noncolitogenic bacterial strains: Common patterns and bacteria strain specific signatures. Inflamm Bowel Dis 2006; 12: 853–862.

25.

Qin

Roberts

Grimm

et al . An obesity-associated gut microbiome reprograms the intestinal epigenome and leads to altered colonic gene expression. Genome Biol 2018; 19: 7.

26.

Larsson

Tremaroli

Lee

et al . Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88. Gut 2012; 61: 1124–1131.

27.

Reikvam

Erofeev

Sandvik

et al . Depletion of murine intestinal microbiota: Effects on gut mucosa and epithelial gene expression. PLoS ONE 2011; 6: e17996.

28.

Dalmasso

Nguyen

Yan

et al . Microbiota modulate host gene expression via microRNAs. PLoS ONE 2011; 6: e19293.

29.

Cresci

Thangaraju

Mellinger

et al . Colonic gene expression in conventional and germ-free mice with a focus on the butyrate receptor GPR109A and the butyrate transporter SLC5A8. J Gastrointest Surg 2010; 14: 449–461.

30.

Fukushima

Ogawa

Takahashi

et al . Non-pathogenic bacteria modulate colonic epithelial gene expression in germ-free mice. Scand J Gastroenterol 2003; 38: 626–634.

31.

Esworthy

Binder

Doroshow

et al . Microflora trigger colitis in mice deficient in selenium-dependent glutathione peroxidase and induce Gpx2 gene expression. Biol Chem 2003; 384: 597–607.

32.

Berer

Gerdes

Cekanaviciute

et al . Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci USA 2017; 114: 10719–10724.