Potential role of indolelactate and butyrate in multiple sclerosis revealed by integrated microbiome-metabolome analysis

Izhak Levi; Michael Gurevich; Gal Perlman; David Magalashvili; Shay Menascu; Noam Bar; Anastasia Godneva; Liron Zahavi; Danyel Chermon; Noa Kosower; Bat Chen Wolf; Gal Malka; Maya Lotan-Pompan; Adina Weinberger; Erez Yirmiya; Daphna Rothschild; Sigal Leviatan; Avishag Tsur; Maria Didkin; Sapir Dreyer; Hen Eizikovitz; Yamit Titngi; Sue Mayost; Polina Sonis; Mark Dolev; Yael Stern; Anat Achiron; Eran Segal

doi:10.1016/j.xcrm.2021.100246

Potential role of indolelactate and butyrate in multiple sclerosis revealed by integrated microbiome-metabolome analysis

Izhak Levi, Michael Gurevich, Gal Perlman, David Magalashvili, Shay Menascu, Noam Bar, Anastasia Godneva, Liron Zahavi, Danyel Chermon, Noa Kosower, Bat Chen Wolf, Gal Malka, Maya Lotan-Pompan, Adina Weinberger, Erez Yirmiya, Daphna Rothschild, Sigal Leviatan, Avishag Tsur, Maria Didkin, Sapir DreyerHen Eizikovitz, Yamit Titngi, Sue Mayost, Polina Sonis, Mark Dolev, Yael Stern, Anat Achiron^*, Eran Segal^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

66 Scopus citations

Abstract

Multiple sclerosis (MS) is an immune-mediated disease whose precise etiology is unknown. Several studies found alterations in the microbiome of individuals with MS, but the mechanism by which it may affect MS is poorly understood. Here we analyze the microbiome of 129 individuals with MS and find that they harbor distinct microbial patterns compared with controls. To study the functional consequences of these differences, we measure levels of 1,251 serum metabolites in a subgroup of subjects and unravel a distinct metabolite signature that separates affected individuals from controls nearly perfectly (AUC = 0.97). Individuals with MS are found to be depleted in butyrate-producing bacteria and in bacteria that produce indolelactate, an intermediate in generation of the potent neuroprotective antioxidant indolepropionate, which we found to be lower in their serum. We identify microbial and metabolite candidates that may contribute to MS and should be explored further for their causal role and therapeutic potential.

Original language	English
Article number	100246
Journal	Cell Reports Medicine
Volume	2
Issue number	4
DOIs	https://doi.org/10.1016/j.xcrm.2021.100246
State	Published - 20 Apr 2021

Funding

Funders	Funder number
Erez MS Fund	40427
Federal German Ministry for Education and Research
Joyce E. Eisenberg Foundation
Peleg MS Fund	40428
White Rose International Foundation
Horizon 2020 Framework Programme	786344
Masonic Charitable Foundation
European Research Council
Minerva Foundation
Else Kröner-Fresenius-Stiftung
Israel Science Foundation
Crown Human Genome Center

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Levi, I., Gurevich, M., Perlman, G., Magalashvili, D., Menascu, S., Bar, N., Godneva, A., Zahavi, L., Chermon, D., Kosower, N., Wolf, B. C., Malka, G., Lotan-Pompan, M., Weinberger, A., Yirmiya, E., Rothschild, D., Leviatan, S., Tsur, A., Didkin, M., ... Segal, E. (2021). Potential role of indolelactate and butyrate in multiple sclerosis revealed by integrated microbiome-metabolome analysis. Cell Reports Medicine, 2(4), Article 100246. https://doi.org/10.1016/j.xcrm.2021.100246

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title = "Potential role of indolelactate and butyrate in multiple sclerosis revealed by integrated microbiome-metabolome analysis",

abstract = "Multiple sclerosis (MS) is an immune-mediated disease whose precise etiology is unknown. Several studies found alterations in the microbiome of individuals with MS, but the mechanism by which it may affect MS is poorly understood. Here we analyze the microbiome of 129 individuals with MS and find that they harbor distinct microbial patterns compared with controls. To study the functional consequences of these differences, we measure levels of 1,251 serum metabolites in a subgroup of subjects and unravel a distinct metabolite signature that separates affected individuals from controls nearly perfectly (AUC = 0.97). Individuals with MS are found to be depleted in butyrate-producing bacteria and in bacteria that produce indolelactate, an intermediate in generation of the potent neuroprotective antioxidant indolepropionate, which we found to be lower in their serum. We identify microbial and metabolite candidates that may contribute to MS and should be explored further for their causal role and therapeutic potential.",

author = "Izhak Levi and Michael Gurevich and Gal Perlman and David Magalashvili and Shay Menascu and Noam Bar and Anastasia Godneva and Liron Zahavi and Danyel Chermon and Noa Kosower and Wolf, {Bat Chen} and Gal Malka and Maya Lotan-Pompan and Adina Weinberger and Erez Yirmiya and Daphna Rothschild and Sigal Leviatan and Avishag Tsur and Maria Didkin and Sapir Dreyer and Hen Eizikovitz and Yamit Titngi and Sue Mayost and Polina Sonis and Mark Dolev and Yael Stern and Anat Achiron and Eran Segal",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2021",

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doi = "10.1016/j.xcrm.2021.100246",

language = "אנגלית",

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Levi, I, Gurevich, M, Perlman, G, Magalashvili, D, Menascu, S, Bar, N, Godneva, A, Zahavi, L, Chermon, D, Kosower, N, Wolf, BC, Malka, G, Lotan-Pompan, M, Weinberger, A, Yirmiya, E, Rothschild, D, Leviatan, S, Tsur, A, Didkin, M, Dreyer, S, Eizikovitz, H, Titngi, Y, Mayost, S, Sonis, P, Dolev, M, Stern, Y, Achiron, A & Segal, E 2021, 'Potential role of indolelactate and butyrate in multiple sclerosis revealed by integrated microbiome-metabolome analysis', Cell Reports Medicine, vol. 2, no. 4, 100246. https://doi.org/10.1016/j.xcrm.2021.100246

TY - JOUR

T1 - Potential role of indolelactate and butyrate in multiple sclerosis revealed by integrated microbiome-metabolome analysis

AU - Levi, Izhak

AU - Gurevich, Michael

AU - Perlman, Gal

AU - Magalashvili, David

AU - Menascu, Shay

AU - Bar, Noam

AU - Godneva, Anastasia

AU - Zahavi, Liron

AU - Chermon, Danyel

AU - Kosower, Noa

AU - Wolf, Bat Chen

AU - Malka, Gal

AU - Lotan-Pompan, Maya

AU - Weinberger, Adina

AU - Yirmiya, Erez

AU - Rothschild, Daphna

AU - Leviatan, Sigal

AU - Tsur, Avishag

AU - Didkin, Maria

AU - Dreyer, Sapir

AU - Eizikovitz, Hen

AU - Titngi, Yamit

AU - Mayost, Sue

AU - Sonis, Polina

AU - Dolev, Mark

AU - Stern, Yael

AU - Achiron, Anat

AU - Segal, Eran

PY - 2021/4/20

Y1 - 2021/4/20

N2 - Multiple sclerosis (MS) is an immune-mediated disease whose precise etiology is unknown. Several studies found alterations in the microbiome of individuals with MS, but the mechanism by which it may affect MS is poorly understood. Here we analyze the microbiome of 129 individuals with MS and find that they harbor distinct microbial patterns compared with controls. To study the functional consequences of these differences, we measure levels of 1,251 serum metabolites in a subgroup of subjects and unravel a distinct metabolite signature that separates affected individuals from controls nearly perfectly (AUC = 0.97). Individuals with MS are found to be depleted in butyrate-producing bacteria and in bacteria that produce indolelactate, an intermediate in generation of the potent neuroprotective antioxidant indolepropionate, which we found to be lower in their serum. We identify microbial and metabolite candidates that may contribute to MS and should be explored further for their causal role and therapeutic potential.

AB - Multiple sclerosis (MS) is an immune-mediated disease whose precise etiology is unknown. Several studies found alterations in the microbiome of individuals with MS, but the mechanism by which it may affect MS is poorly understood. Here we analyze the microbiome of 129 individuals with MS and find that they harbor distinct microbial patterns compared with controls. To study the functional consequences of these differences, we measure levels of 1,251 serum metabolites in a subgroup of subjects and unravel a distinct metabolite signature that separates affected individuals from controls nearly perfectly (AUC = 0.97). Individuals with MS are found to be depleted in butyrate-producing bacteria and in bacteria that produce indolelactate, an intermediate in generation of the potent neuroprotective antioxidant indolepropionate, which we found to be lower in their serum. We identify microbial and metabolite candidates that may contribute to MS and should be explored further for their causal role and therapeutic potential.

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U2 - 10.1016/j.xcrm.2021.100246

DO - 10.1016/j.xcrm.2021.100246

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C2 - 33948576

AN - SCOPUS:85104371258

SN - 2666-3791

VL - 2

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 4

M1 - 100246

ER -

Potential role of indolelactate and butyrate in multiple sclerosis revealed by integrated microbiome-metabolome analysis

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