Associations between gut microbiota and sleep: a two-sample, bidirectional Mendelian randomization study

Abstract

IntroductionPrevious research has reported that the gut microbiota performs an essential role in sleep through the microbiome–gut–brain axis. However, the causal association between gut microbiota and sleep remains undetermined.MethodsWe performed a two-sample, bidirectional Mendelian randomization (MR) analysis using genome-wide association study summary data of gut microbiota and self-reported sleep traits from the MiBioGen consortium and UK Biobank to investigate causal relationships between 119 bacterial genera and seven sleep-associated traits. We calculated effect estimates by using the inverse-variance weighted (as the main method), maximum likelihood, simple model, weighted model, weighted median, and MR-Egger methods, whereas heterogeneity and pleiotropy were detected and measured by the MR pleiotropy residual sum and outlier method, Cochran’s Q statistics, and MR-Egger regression.ResultsIn forward MR analysis, inverse-variance weighted estimates concluded that the genetic forecasts of relative abundance of 42 bacterial genera had causal effects on sleep-associated traits. In the reverse MR analysis, sleep-associated traits had a causal effect on 39 bacterial genera, 13 of which overlapped with the bacterial genera in the forward MR analysis.DiscussionIn conclusion, our research indicates that gut microbiota may be involved in the regulation of sleep, and conversely, changes in sleep-associated traits may also alter the abundance of gut microbiota. These findings suggest an underlying reciprocal causal association between gut microbiota and sleep.

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“…Two-sample mendelian randomization (TSMR) was performed in the analysis. Single nucleotide polymorphisms (SNPs) were randomly allocated at conception, determining that SNPs were not affected by post environmental factors [22].…”

“…Mendelian randomization (MR) is a commonly utilized causal inference approach that uses single nucleotide polymorphisms (SNPs) associated with the exposure of interest as instruments to evaluate its impact on outcomes [22]. To explore whether a causal relationship exists between esophageal cancer and PRKCB, we conducted causal inference using the two-sample MR methodology.…”

Nutraceutical blends predict enhanced health via microbiota reshaping improving cytokines and life quality: a Brazilian double-blind randomized trial

“…However, keeping a healthy lifestyle is increasingly challenging nowadays, especially regarding diet and good sleep quality 9 . External factors, such as disruptions in the body's internal clock 10 , over-stimulating environments 11 , 12 , dietary habits 13 , 14 ,and gut dysbiosis 15 – 17 , might directly affect sleep quality. Furthermore, intrinsic factors such as the neuro-immune-endocrine axis, which encompasses neuroendocrine elements like the hypothalamic–pituitary–adrenal (HPA) axis, and the enteric nervous system (ENS), along with immune factors typified by the sympathoadrenal axis (gut-lymphoid connection) 18 ; play a crucial role in regulating sleep quality, immune response, and hormonal balance 15 , 19 .…”

“…Regarding the gut microbiota composition, it is crucial to highlight the reduction in Bacteroidetes phylum abundance associated with sleep disorders 17 and the enhancement of sleep quality 28 , 29 . Especially the Bacteroides and Prevotella genera abundance has been associated with an improvement in metabolites renowned as good sleep quality promoters 16 , 17 , 29 , 30 .…”

“…Regarding the gut microbiota composition, it is crucial to highlight the reduction in Bacteroidetes phylum abundance associated with sleep disorders 17 and the enhancement of sleep quality 28 , 29 . Especially the Bacteroides and Prevotella genera abundance has been associated with an improvement in metabolites renowned as good sleep quality promoters 16 , 17 , 29 , 30 . Also, the Alistipes onderdonkii species, included in the Bacteroidetes phylum, has recently gained attention as a microbiota marker associated with inflammation and mental health implications, besides its role in cardiometabolic protection 30 , 31 .…”