Gut microbiota associations with common diseases and prescription medications in a population-based cohort

Jackson, Matthew A.; Verdi, Serena; Maxan, Maria Emanuela; Shin, Cheol Min; Zierer, Jonas; Bowyer, Ruth C E; Martin, Tiphaine; Williams, Frances; Menni, Cristina; Bell, Jordana T.; Spector, Timothy D.; Steves, Claire J.

doi:10.1038/s41467-018-05184-7

Cited by 430 publications

(315 citation statements)

References 29 publications

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“…The microbiota can benefit host health by producing essential nutrients, digesting otherwise indigestible food components, and enhancing maturation of the immune system . An unhealthy imbalance in the microbiota community composition, called dysbiosis, is linked to a variety of metabolic, inflammatory, and immunologic diseases . Dysbiosis is also linked to increased intestinal permeability/leaky gut .…”

Section: Introductionmentioning

confidence: 99%

“…(42,43) An unhealthy imbalance in the microbiota community composition, called dysbiosis, is linked to a variety of metabolic, inflammatory, and immunologic diseases. (44)(45)(46)(47) Dysbiosis is also linked to increased intestinal permeability/leaky gut. (42,48) A leaky intestinal barrier allows translocation of bacteria and their products into the lamina propria where they can activate immune cells, cause inflammation, and enter the systemic circulation.…”

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confidence: 99%

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Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

Schepper

Collins

Rios‐Arce

et al. 2019

Journal of Bone and Mineral Research

107

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Glucocorticoids (GCs) are potent immune‐modulating drugs with significant side effects, including glucocorticoid‐induced osteoporosis (GIO). GCs directly induce osteoblast and osteocyte apoptosis but also alter intestinal microbiota composition. Although the gut microbiota is known to contribute to the regulation of bone density, its role in GIO has never been examined. To test this, male C57/Bl6J mice were treated for 8 weeks with GC (prednisolone, GC‐Tx) in the presence or absence of broad‐spectrum antibiotic treatment (ABX) to deplete the microbiota. Long‐term ABX prevented GC‐Tx‐induced trabecular bone loss, showing the requirement of gut microbiota for GIO. Treatment of GC‐Tx mice with a probiotic (Lactobacillus reuteri [LR]) prevented trabecular bone loss. Microbiota analyses indicated that GC‐Tx changed the abundance of Verrucomicobiales and Bacteriodales phyla and random forest analyses indicated significant differences in abundance of Porphyromonadaceae and Clostridiales operational taxonomic units (OTUs) between groups. Furthermore, transplantation of GC‐Tx mouse fecal material into recipient naïve, untreated WT mice caused bone loss, supporting a functional role for microbiota in GIO. We also report that GC caused intestinal barrier breaks, as evidenced by increased serum endotoxin level (2.4‐fold), that were prevented by LR and ABX treatments. Enhancement of barrier function with a mucus supplement prevented both GC‐Tx–induced barrier leakage and trabecular GIO. In bone, treatment with ABX, LR or a mucus supplement reduced GC‐Tx–induced osteoblast and osteocyte apoptosis. GC‐Tx suppression of Wnt10b in bone was restored by the LR and high‐molecular‐weight polymer (MDY) treatments as well as microbiota depletion. Finally, we identified that bone‐specific Wnt10b overexpression prevented GIO. Taken together, our data highlight the previously unappreciated involvement of the gut microbiota and intestinal barrier function in trabecular GIO pathogenesis (including Wnt10b suppression and osteoblast and osteocyte apoptosis) and identify the gut as a novel therapeutic target for preventing GIO. © 2019 American Society for Bone and Mineral Research.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

Schepper

Collins

Rios‐Arce

et al. 2019

Journal of Bone and Mineral Research

107

View full text Add to dashboard Cite

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“…A variety of environmental and clinical factors including diet, lifestyle, diseases and medications can induce substantial shifts in the microbiome composition [13,14]. Multiple studies have shown that diet and medications are the main forces influencing gut microbial diversity [15,16,17,18,19,20,21,22]. Yet, they only explain a small percentage of the microbiome variation observed in the human population.…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Assessment of Demographic, Environmental and Host Genetic Associations with Gut Microbiome Diversity in Healthy Individuals

Šćepanović

Hodel

Mondot

et al. 2019

Preprint

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Background. The gut microbiome is an important determinant of human health. Its composition has been shown to be influenced by multiple environmental factors and likely by host genetic variation. In the framework of the Milieu Intérieur Consortium, a total of 1,000 healthy individuals of western European ancestry, with a 1:1 sex ratio and evenly stratified across five decades of life (age 20 -69), were recruited. We generated 16S ribosomal RNA profiles from stool samples for 858 participants. We investigated genetic and non-genetic factors that contribute to individual differences in fecal microbiome composition.Results. Among 110 demographic, clinical and environmental factors, 11 were identified as significantly correlated with α-diversity, ß-diversity or abundance of specific microbial communities in multivariable models. Age and blood alanine aminotransferase levels showed the strongest associations with microbiome diversity. In total, all non-genetic factors explained 16.4% of the variance. We then searched for associations between >5 million single nucleotide polymorphisms and the same indicators of fecal microbiome diversity, including the significant non-genetic factors as covariates. No genome-wide significant associations were identified after correction for multiple testing. A small fraction of previously reported associations between human genetic variants and specific taxa could be replicated in our cohort, while no replication was observed for any of the diversity metrics. Conclusion.In a well-characterized cohort of healthy individuals, we identified several nongenetic variables associated with fecal microbiome diversity. In contrast, host genetics only had a negligible influence. Demographic and environmental factors are thus the main contributors to fecal microbiome composition in healthy individuals.

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“…In contrast, relatively common medications, beta-blockers and proton pump inhibitors were taken by only 7 and 4 individuals respectively. Despite this, medication usage was a significant albeit minor contributor (R 2 = 0.003) to microbial community composition, highlighting how xenobiotics can, and do influence the gut microbiome (Jackson et al, 2018;Maier et al, 2018).…”

Section: Variable Gut Microbiomes In a Restricted Geographical Regionmentioning

confidence: 99%

Stability and dynamics of the human gut microbiome and its association with systemic immune traits

Byrd¹,

Liu

Fujimura³

et al. 2020

Preprint

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Analysis of 1,363 deeply sequenced gut microbiome samples from 946 healthy donors of the Milieu Intérieur cohort provides new opportunities to discover how the gut microbiome is associated with host factors and lifestyle parameters. Using a genomebased taxonomy to achieve higher resolution analysis, we found an enrichment of Prevotella species in males, and that bacterial profiles are dynamic across five decades of life (20-69), with Bacteroidota species consistently increased with age while Actinobacteriota species, including Bifidobacterium, decreased. Longitudinal sampling revealed short-term stability exceeds inter-individual differences; however, the degree of stability was variable between donors and influenced by their baseline community composition. We then integrated the microbiome results with systemic immunophenotypes to show that host/microbe associations discovered in animal models, such as T regulatory cells and short chain fatty acids, could be validated in human data.These results will enable personalized medicine approaches for microbial therapeutics and biomarkers. ¶ unless otherwise indicated, partners are located at

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Gut microbiota associations with common diseases and prescription medications in a population-based cohort

Cited by 430 publications

References 29 publications

Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

A Comprehensive Assessment of Demographic, Environmental and Host Genetic Associations with Gut Microbiome Diversity in Healthy Individuals

Stability and dynamics of the human gut microbiome and its association with systemic immune traits

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