Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity

Zhernakova, Alexandra; Kurilshikov, Alexander; Bonder, Marc Jan; Tigchelaar, Ettje F.; Schirmer, Melanie; Vatanen, Tommi; Mujagic, Zlatan; Vila, Arnau Vich; Falony, Gwen; Vieira-Silva, Sara; Wang, Jun; Imhann, Floris; Brandsma, Eelke; Jankipersadsing, Soesma A; Joossens, Marie; Cenit, María Carmen; Deelen, Patrick; Swertz, Morris A.; Weersma, Rinse K.; Feskens, Edith J. M.; Netea, Mihai G.; Gevers, Dirk; Jonkers, Daisy; Franke, Lude; Aulchenko, Yurii S.; Huttenhower, Curtis; Raes, Jeroen; Hofker, Marten H.; Xavier, Ramnik J.; Wijmenga, Cisca; Fu, Jingyuan

doi:10.1126/science.aad3369

Cited by 1,403 publications

(1,261 citation statements)

References 52 publications

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“…For example, high intestinal permeability individuals tended to consume less wine and more spirits than low intestinal permeability patients (Leclercq et al, 2014b). Additionally, red wine consumption has been associated with higher microbial diversity and enhancement of bacterial species that convey anti-inflammatory properties (Zhernakova et al, 2016). Thus, perhaps types of alcoholic beverages, or specific components of certain alcohols, have differential effects on behaviors associated with AUD and must therefore be controlled for in future investigations.…”

Section: Future Directionsmentioning

confidence: 99%

The Microbiota, the Gut and the Brain in Eating and Alcohol Use Disorders: A ‘Ménage à Trois’?

Temko

Bouhlal

Farokhnia

et al. 2017

Alcohol and Alcoholism

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Aims: Accumulating evidence for the influence of the gut microbiota on the bidirectional communication along the gut-brain axis suggests a role of the gut microbiota in eating disorders (EDs) and alcohol and substance use disorders. The potential influence of altered gut microbiota (dysbiosis) on behaviors associated with such disorders may have implications for developing therapeutic interventions. Methods: A systematic review of preclinical and clinical studies evaluating the gut microbiota, EDs and alcohol and substance use disorders was conducted using MEDLINE, Embase and Web of Science databases with the objective being to examine the role of the gut microbiota in behavioral correlates of these disorders. Original papers focused on the gut microbiota and potential behavioral implications were deemed eligible for consideration. Results: The resulting 12 publications were limited to gut microbiota studies related to EDs and alcohol and substance use disorders. Some studies suggest that dysbiosis and gut microbial byproducts may influence the pathophysiology of EDs via direct and indirect interference with peptide hormone signaling. Additionally, dysbiosis was shown to be correlated with alcohol use disorder-related symptoms, i.e. craving, depression and anxiety. Finally, a mouse study suggests that manipulations in the gut microbiota may affect cocaine-related behaviors. Conclusions: Promising, albeit preliminary, findings suggest a potential role of the gut microbiota in behavioral correlates of EDs and alcohol and substance use disorders. Short summary: Preliminary evidence exists supporting the role of the gut microbiota in eating disorders and alcohol and substance use disorders, although additional investigation is needed to determine what is causative versus epiphenomenological.

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Section: Future Directionsmentioning

confidence: 99%

The Microbiota, the Gut and the Brain in Eating and Alcohol Use Disorders: A ‘Ménage à Trois’?

Temko

Bouhlal

Farokhnia

et al. 2017

Alcohol and Alcoholism

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“…First, there is an excessive bacterial similarity among individuals sharing a household, but no such similarity was observed across family members without a history of household sharing [8,20,22,35]. Second, over 20% of gut microbiome β-diversity variance can be inferred via several measured environmental factors, such as answers to food frequency and drug use questionnaires [8,33,34], whereas no statistically significant result was obtained when applying a similar methodology to genetic variants [8]. These results further demonstrate that the gut microbiome is predominantly shaped by environmental factors.…”

Section: The Microbiome Is Predominantly Shaped By Non-genetic Factorsmentioning

confidence: 99%

“…Recent studies employing these technologies have uncovered evidence for both environmental and host genetic association with the microbiome composition [8,11,20,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. However, to date there is no consensus regarding how and to what extent does host genetics shapes the gut microbiome, as compared to environmental factors.…”

Section: Introductionmentioning

confidence: 99%

Host genetics and microbiome associations from the lens of genome wide association studies

Weissbrod

Rothschild

Barkan

et al. 2018

Preprint

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Recent studies indicate that the gut microbiome is partially heritable, motivating the need to investigate microbiome-host genome associations via microbial genome-wide association studies (mGWAS). Existing mGWAS demonstrate that microbiome-host genotypes associations are typically weak and are spread across multiple variants, similar to associations often observed in genome-wide association studies (GWAS) of complex traits. Here we reconsider mGWAS by viewing them through the lens of GWAS, and demonstrate that there are striking similarities between the challenges and pitfalls faced by the two study designs. We further advocate the mGWAS community to adopt three key lessons learned over the history of GWAS: (a) Adopting uniform data and reporting formats to facilitate replication and meta-analysis efforts; (b) enforcing stringent statistical criteria to reduce the number of false positive findings; and (c) considering the microbiome and the host genome as distinct entities, rather than studying different taxa and single nucleotide polymorphism (SNPs) separately. Finally, we anticipate that mGWAS sample sizes will have to increase by orders of magnitude to reproducibly associate the host genome with the gut microbiome.PeerJ Preprints | https://doi.org/10.7287/peerj.preprints.26615v1 | CC BY 4.0 Open Access | rec: 5

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“…Whether these early life events are determinants of microbiota-related disease in later life remains to be established. Prospective large cohort studies addressing these factors in relation to microbiota composition will provide important insight into the role of the intestinal microbiota in the (patho)physiology of disease [10,11].…”

Section: Bbbmentioning

confidence: 99%

Emerging role of intestinal microbiota and microbial metabolites in metabolic control

Herrema

IJzerman²,

Nieuwdorp

2016

Diabetologia

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The role of the intestinal microbiota and microbial metabolites in the maintenance of host health and development of metabolic disease has gained significant attention over the past decade. Mechanistic insight revealing causality, however, is scarce. Work by Ussar and co-workers demonstrates that a complex interaction between microbiota, host genetics and environmental factors is involved in metabolic disease development in mice. In addition, Perry and coworkers show that the microbial metabolite acetate augments insulin resistance in rats. These studies underscore an important role of the microbiota in the development of obesity and symptoms of type 2 diabetes in rodents. If causality can be demonstrated in humans, development of novel diagnostic and therapeutic tools that target the gut microbiota will have high potential.Keywords Gut microbiota . Insulin resistance . Obesity . Short-chain fatty acids . Type 2 diabetes Abbreviations BBB Blood-brain barrier FMT Faecal microbiota transfer GSIS Glucose-stimulated insulin secretion HFD High-fat diet ICV Intracerebroventricular SCFA Short-chain fatty acidThe symbiotic relationship with our intestinal microbiota is exemplified by a broad range of beneficial effects for the host metabolism, including digestion of complex carbohydrates and maturation of the immune response. In addition, the intestinal microbiota serves an endocrine role by producing a vast amount of metabolites with the potential to modulate host metabolism [1]. The intestinal microbiota has, as such, also been implicated in the development of obesity and type 2 diabetes in human and rodent models [2]. This adds another layer of complexity to studying the origin of these multifactorial metabolic pathologies that arise from a complicated interplay between genetic risk factors and external factors, including dietary intake and physical activity. This commentary discusses two recent rodent studies on the potential importance of the intestinal microbiota in metabolic disease. Ussar and co-workers [3] studied the complex interaction between environmental and genetic factors in microbiota-related metabolic disease development in mice, while Perry and co-workers [4] investigated a potential mechanism underlying microbiota-driven disease development using a rat model.Colonisation of the gastrointestinal tract starts as early as in utero [5], and a core microbiome composed mainly of Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria and Verrucomicrobia is established around the third year of life. Extrinsic factors, including host genetic makeup [6], cohousing/family members [7], oral antibiotic use early in life [8] and diet [9] are dominating factors in shaping the intestinal microbiota. Whether these early life events are determinants of microbiota-related disease in later life remains to be

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Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity

Cited by 1,403 publications

References 52 publications

The Microbiota, the Gut and the Brain in Eating and Alcohol Use Disorders: A ‘Ménage à Trois’?

The Microbiota, the Gut and the Brain in Eating and Alcohol Use Disorders: A ‘Ménage à Trois’?

Host genetics and microbiome associations from the lens of genome wide association studies

Emerging role of intestinal microbiota and microbial metabolites in metabolic control

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