Analysis of 1135 gut metagenomes identifies sex-specific resistome profiles

Trishla Sinha; Arnau Vich Vila; Sanzhima Garmaeva; Soesma A Jankipersadsing; Floris Imhann; Valerie Collij; Marc Jan Bonder; Xiaofang Jiang; Thomas Gurry; Eric J Alm; Mauro D'Amato; Rinse K Weersma; Sicco Scherjon; Cisca Wijmenga; Jingyuan Fu; Alexander Kurilshikov; Alexandra Zhernakova

doi:10.1080/19490976.2018.1528822

Analysis of 1135 gut metagenomes identifies sex-specific resistome profiles

Gut Microbes. 2019;10(3):358-366. doi: 10.1080/19490976.2018.1528822. Epub 2018 Oct 29.

Authors

Trishla Sinha¹, Arnau Vich Vila^{1

2}, Sanzhima Garmaeva¹, Soesma A Jankipersadsing^{1

3}, Floris Imhann^{1

2}, Valerie Collij², Marc Jan Bonder¹, Xiaofang Jiang^{4

5}, Thomas Gurry^{4

5}, Eric J Alm^{4

5

6}, Mauro D'Amato^{7

8}, Rinse K Weersma², Sicco Scherjon⁹, Cisca Wijmenga^{1

10}, Jingyuan Fu^{1

3}, Alexander Kurilshikov¹, Alexandra Zhernakova¹

Affiliations

¹ a Department of Genetics , University of Groningen, University Medical Center Groningen , Groningen , the Netherlands.
² b Department of Gastroenterology and Hepatology , University of Groningen, University Medical Center Groningen , Groningen , the Netherlands.
³ c Department of Pediatrics , University of Groningen, University Medical Center Groningen , Groningen , the Netherlands.
⁴ d Department of Biological Engineering , Massachusetts Institute of Technology , Cambridge , MA , USA.
⁵ e Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology , Cambridge , MA , USA.
⁶ f The Broad Institute of MIT and Harvard , Cambridge , MA , USA.
⁷ g Gastrointestinal Genetics Unit , Biodonostia Health Research Institute , San Sebastian , Spain.
⁸ h Ikerbasque, Basque Foundation for Science , Bilbao , Spain.
⁹ i Department of Obstetrics and Gynecology , University of Groningen, University Medical Center Groningen , Groningen , the Netherlands.
¹⁰ j Department of Immunology , K.G. Jebsen Coeliac Disease Research Centre, University of Oslo , Oslo , Norway.

Abstract

Several gastrointestinal diseases show a sex imbalance, although the underlying (patho)physiological mechanisms behind this are not well understood. The gut microbiome may be involved in this process, forming a complex interaction with host immune system, sex hormones, medication and other environmental factors. Here we performed sex-specific analyses of fecal microbiota composition in 1135 individuals from a population-based cohort. The overall gut microbiome composition of females and males was significantly different (p = 0.001), with females showing a greater microbial diversity (p = 0.009). After correcting for the effects of intrinsic factors, smoking, diet and medications, female hormonal factors such as the use of oral contraceptives and undergoing an ovariectomy were associated with microbial species and pathways. Females had a higher richness of antibiotic-resistance genes, with the most notable being resistance to the lincosamide nucleotidyltransferase (LNU) gene family. The higher abundance of resistance genes is consistent with the greater prescription of the Macrolide-Lincosamide-Streptogramin classes of antibiotics to females. Furthermore, we observed an increased resistance to aminoglycosides in females with self-reported irritable bowel syndrome. These results throw light upon the effects of common medications that are differentially prescribed between sexes and highlight the importance of sex-specific analysis when studying the gut microbiome and resistome.

Keywords: female hormonal factors; gut microbiome; gut resistome; sex differences.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Anti-Bacterial Agents / pharmacology*
Biodiversity*
Drug Resistance, Microbial / genetics*
Feces / microbiology
Female
Gastrointestinal Microbiome / genetics*
Genes, Bacterial / genetics
Humans
Irritable Bowel Syndrome / microbiology
Lincosamides / pharmacology
Male
Metagenome / genetics*
Middle Aged
Prospective Studies
Sex Factors
Young Adult

Substances

Anti-Bacterial Agents
Lincosamides

Grants and funding

C.W. holds a European Research Council (ERC) advanced grant (FP/2007-2013/ERC grant 2012-322698), a Netherlands Organization for Scientific Research (NWO) Spinoza prize (NWO SPI 92-266), and is partly supported by the Stiftelsen Kristian Gerhard Jebsen Foundation (Norway). A.Z. holds an ERC starting grant (715772), and NWO-VIDI grant 016.178.056. A.Z. and J.F. are funded by CardioVasculair Onderzoek Nederland (CVON 2012-03). J.F. and R.W. are funded by an NWO-VIDI grant 864.13.013 and ZonMW-VIDI grant 016.136.308, respectively. T.S and S.G hold scholarships from the Junior Scientific Masterclass, University of Groningen and the Graduate School of Medical Sciences, University of Groningen, respectively. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript;European Research Council [715772];European Research Council [FP/2007-2013/ERC grant 2012-322698];Nederlandse Organisatie voor Wetenschappelijk Onderzoek [NWO SPI 92-266];Nederlandse Organisatie voor Wetenschappelijk Onderzoek [016.178.056];Nederlandse Organisatie voor Wetenschappelijk Onderzoek [864.13.013];Graduate School of Medical Sciences, University of Groningen. [None];Junior Scientific Masterclass, University of Groningen [None];Stiftelsen Kristian Gerhard Jebsen;ZonMw [016.136.308];