The metabolic potential of the paediatric-onset multiple sclerosis gut microbiome

被引：9

作者：

Mirza, Ali, I ^{[1
]}

Zhu, Feng ^{[1
]}

Knox, Natalie ^{[2
,3
]}

Forbes, Jessica D. ^{[4
,5
]}

Bonner, Christine ^{[2
]}

Van Domselaar, Gary ^{[2
,3
]}

Bernstein, Charles N. ^{[6
,7
]}

Graham, Morag ^{[2
,3
]}

Marrie, Ruth Ann ^{[6
,8
]}

Hart, Janace ^{[9
]}

Yeh, E. Ann ^{[10
]}

Arnold, Douglas L. ^{[11
]}

Bar-Or, Amit ^{[12
,13
]}

O'Mahony, Julia ^{[10
]}

Zhao, Yinshan ^{[1
]}

Hsiao, William ^{[14
]}

Banwell, Brenda ^{[15
]}

Waubant, Emmanuelle ^{[9
]}

Tremlett, Helen ^{[1
]}

机构：

[1] Univ British Columbia, Dept Med Neurol, Vancouver, BC, Canada

[2] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada

[3] Univ Manitoba, Dept Med Microbiol & Infect Dis, Winnipeg, MB, Canada

[4] Roy Romanow Prov Lab, Regina, SK, Canada

[5] Univ Saskatchewan, Coll Med, Dept Pathol & Lab Med, Saskatoon, SK, Canada

[6] Univ Manitoba, Max Rady Coll Med, Rady Fac Hlth Sci, Dept Internal Med, Winnipeg, MB, Canada

[7] Univ Manitoba, Inflammatory Bowel Dis Clin & Res Ctr, Winnipeg, MB, Canada

[8] Univ Manitoba, Max Rady Coll Med, Rady Fac Hlth Sci, Dept Community Hlth Sci, Winnipeg, MB, Canada

[9] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA

[10] Univ Toronto, Hosp Sick Children, Dept Pediat Neurol, Toronto, ON, Canada

[11] McGill Univ, Dept Neurol & Neurosurg, Fac Med, Room S126,2211 Wesbrook Mall, Montreal, PQ V6T 2B5, Canada

[12] Univ Penn Perelman, Ctr Neuroinflammat & Expt Therapeut, Sch Med, Philadelphia, PA USA

[13] Univ Penn Perelman, Dept Neurol, Sch Med, Philadelphia, PA USA

[14] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC, Canada

[15] Childrens Hosp Philadelphia, Philadelphia, PA USA

来源：

MULTIPLE SCLEROSIS AND RELATED DISORDERS | 2022年 / 63卷

关键词：

Gut microbiome; Multiple sclerosis; Metagenomics; Metabolome; Metabolism; Microbial metabolites; CAZymes;

D O I：

10.1016/j.msard.2022.103829

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: The aim of this study was to examine the gut microbiome's metabolic potential in paediatric-onset MS patients (symptom onset < 18 years). Methods: We included 17 MS participants and 20 controls similar for sex, age, race, and stool consistency from the Canadian Paediatric Demyelinating Disease Network study. Stool-derived gut metagenome gene abundances were used to estimate relative abundances and turnover scores of individual microbial metabolites and the composition and diversity of carbohydrate-active enzymes (CAZymes). MS participants and controls were compared using the Wilcoxon rank-sum test, as were the disease-modifying drug (DMD) exposed and naive MS participants. Results: The median age(s) at MS symptom onset=16.1 years (interquartile range [IQR]=1.7), and at stool sample procurement=16.9/15.8 years (IQR=2.0/1.4), for the MS participants/controls. Most MS and control participants were girls (80-82%). Five (29%) of the MS participants had never been exposed to a DMD pre-stool sample and 12 (71%) had (7 to beta-interferon and 5 glatiramer acetate). While the relative abundance of metabolites did not differ between MS participants and controls, turnover scores did. MS participants had a greater potential to metabolize lipopolysaccharides than controls (score difference=1.6E-04, p = 0.034) but lower potential to metabolize peptidoglycan molecules and starch (score differences < 2.2E-02, p < 0.040). Further, although CAZymes diversity did not differ (p > 0.050), starch-degrading subfamilies were underrepresented in MS participants versus controls (relative abundance differences >-0.34, p < 0.040) and in the DMD exposed verses DMD naive MS participants (relative abundance differences >-0.20, p < 0.049). Conclusion: Paediatric-onset MS participants had an altered gut microbiome-related metabolic potential compared to controls, including higher breakdown of lipopolysaccharide molecules, but lower resistant starch metabolism.

引用

页数：5

共 15 条

[1] Tandem repeats finder: a program to analyze DNA sequences [J].

Benson, G .

NUCLEIC ACIDS RESEARCH, 1999, 27 (02) :573-580

[2] Relative validation of Block Kids Food Screener for dietary assessment in children and adolescents [J].

Hunsberger, Monica ;

O'Malley, Jean ;

Block, Torin ;

Norris, Jean C. .

MATERNAL AND CHILD NUTRITION, 2015, 11 (02) :260-270

[3] Alterations of the human gut microbiome in multiple sclerosis [J].

Jangi, Sushrut ;

Gandhi, Roopali ;

Cox, Laura M. ;

Li, Ning ;

von Glehn, Felipe ;

Yan, Raymond ;

Patel, Bonny ;

Mazzola, Maria Antonietta ;

Liu, Shirong ;

Glanz, Bonnie L. ;

Cook, Sandra ;

Tankou, Stephanie ;

Stuart, Fiona ;

Melo, Kirsy ;

Nejad, Parham ;

Smith, Kathleen ;

Topcuolu, Begum D. ;

Holden, James ;

Kivisakk, Pia ;

Chitnis, Tanuja ;

De Jager, Philip L. ;

Quintana, Francisco J. ;

Gerber, Georg K. ;

Bry, Lynn ;

Weiner, Howard L. .

NATURE COMMUNICATIONS, 2016, 7

[4] A Metagenome-Wide Association Study of Gut Microbiome in Patients With Multiple Sclerosis Revealed Novel Disease Pathology [J].

Kishikawa, Toshihiro ;

Ogawa, Kotaro ;

Motooka, Daisuke ;

Hosokawa, Akiko ;

Kinoshita, Makoto ;

Suzuki, Ken ;

Yamamoto, Kenichi ;

Masuda, Tatsuo ;

Matsumoto, Yuki ;

Nii, Takuro ;

Maeda, Yuichi ;

Nakamura, Shota ;

Inohara, Hidenori ;

Mochizuki, Hideki ;

Okuno, Tatsusada ;

Okada, Yukinori .

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 2020, 10

[5] Untargeted metabolomics analysis reveals key pathways responsible for the synergistic killing of colistin and doripenem combination against Acinetobacter baumannii [J].

Maifiah, Mohd Hafidz Mahamad ;

Creek, Darren J. ;

Nation, Roger L. ;

Forrest, Alan ;

Tsuji, Brian T. ;

Velkov, Tony ;

Li, Jian .

SCIENTIFIC REPORTS, 2017, 7

[6] Predictive metabolomic profiling of microbial communities using amplicon or metagenomic sequences [J].

Mallick, Himel ;

Franzosa, Eric A. ;

McIver, Lauren J. ;

Banerjee, Soumya ;

Sirota-Madi, Alexandra ;

Kostic, Aleksandar D. ;

Clish, Clary B. ;

Vlamakis, Hera ;

Xavier, Ramnik J. ;

Huttenhower, Curtis .

NATURE COMMUNICATIONS, 2019, 10 (1)

[7] MUSiCC: a marker genes based framework for metagenomic normalization and accurate profiling of gene abundances in the microbiome [J].

Manor, Ohad ;

Borenstein, Elhanan .

GENOME BIOLOGY, 2015, 16

[8] Metagenomic Analysis of the Pediatric-Onset Multiple Sclerosis Gut Microbiome [J].

Mirza, Ali, I ;

Zhu, Feng ;

Knox, Natalie ;

Forbes, Jessica D. ;

Van Domselaar, Gary ;

Bernstein, Charles N. ;

Graham, Morag ;

Marrie, Ruth Ann ;

Hart, Janace ;

Yeh, E. Ann ;

Arnold, Douglas L. ;

Bar-Or, Amit ;

O'Mahony, Julia ;

Zhao, Yinshan ;

Hsiao, William ;

Banwell, Brenda ;

Waubant, Emmanuelle ;

Tremlett, Helen .

NEUROLOGY, 2022, 98 (10) :E1050-E1063

[9] Gut microbial molecules in behavioural and neurodegenerative conditions [J].

Needham, Brittany D. ;

Kaddurah-Daouk, Rima ;

Mazmanian, Sarkis K. .

NATURE REVIEWS NEUROSCIENCE, 2020, 21 (12) :717-731

[10] Metabolic Model-Based Integration of Microbiome Taxonomic and Metabolomic Profiles Elucidates Mechanistic Links between Ecological and Metabolic Variation [J].

Noecker, Cecilia ;

Eng, Alexander ;

Srinivasan, Sujatha ;

Theriot, Casey M. ;

Young, Vincent B. ;

Jansson, Janet K. ;

Fredricks, David N. ;

Borenstein, Elhanan .

MSYSTEMS, 2016, 1 (01)

← 1 2 →