A Two-Sample Mendelian Randomization Analysis Investigates Associations between Gut Microbiota and Celiac Disease

García-Santisteban, Iraia; Cilleros-Portet, Ariadna; Moyua-Ormazabal, Elisabet; Kurilshikov, Alexander; Zhernakova, Alexandra; García-Etxebarria, Koldo; Fernández-Jiménez, Nora; Bilbao, José Ramón

doi:10.20944/preprints202003.0388.v1

Cited by 4 publications

(2 citation statements)

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“…From an intervention point of view, the current evidence shows that inter-individual variation in the gut microbiome composition is mainly due to non-genetic factors, i.e., diet, exercise, and medication [17] and, therefore, the gut microbiome primarily contributes to the non-genetic etiology of mental health disorders. However, exceptions to this pattern exist [18, 19]. Thus, modulation of the gut microbiome by pre- and pro-biotics and other dietary or lifestyle interventions is an essential avenue for preventing and treating mental health and other conditions (for instance, see [20]).…”

Section: Introductionmentioning

confidence: 99%

Mental Health Symptom Reduction Using Digital Therapeutics Care Informed by Genomic SNPs and Gut Microbiome Signatures

Pedroso¹,

Kumbhare²,

Joshi³

et al. 2022

Preprint

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BackgroundMental health diseases are a major component of morbidity and health care costs. Obesity and gut disorders are comorbid with mental health, with the gut microbiome hypothesized to play a key mechanistic role in linking them. Pharmacological and behavioral interventions are currently used to treat mental health disorders, but they have limited efficacy. Dietary and weight-loss interventions have been shown to provide different benefits. Still, there exists conflicting evidence regarding their effects which may be due to an individual’s genetic or microbiome factors modulating the improvement of symptoms.ObjectiveWe aimed to identify genetic and gut microbiome factors that explain the improvement in mental health after a dietary and lifestyle intervention for weight loss.MethodsWe recruited 369 individuals participating in the Digbi Health personalized digital care program, for which we evaluated the association between 23 genetic scores, the abundance of 178 gut microbiome genera, and 42 gut-brain modules (pathways related to neuroactive metabolites produced by gut microbes) with the presence/absence of anxiety/depression or sleep problems at baseline and improvement on anxiety, depression, and insomnia after losing at least 2% body weight.ResultsThe mean BMI and age of the study cohort were 34.6 and 48.7, respectively, and there was an overrepresentation of individuals with functional gastrointestinal disorders (84%). On average, the individuals lost 5.4% of body weight at the time of follow-up (mean of 88 days), and more than 95% reported improvement in at least one outcome. We found significant correlations between genetic scores with anxiety and depression at baseline, gut microbial functions with sleep problems at baseline, and genetic scores and gut microbial taxa and functions with anxiety, depression, and insomnia improvement. Among the gut microbial functions identified, the abundance of butyrate synthesis genes was associated with less than average improvement in depression symptoms, the abundance of kynurenine synthesis genes was associated with less than average improvement in anxiety symptoms, and the abundance of genes able to synthesize and degrade neuroactive hormones like nitric oxide was associated with greater than average improvement in depression and insomnia symptoms. Among the genetic scores identified, anxiety or depression at baseline were associated with genetic scores for alcohol use disorder and major depressive disorder, and greater than average improvement in anxiety and depression symptoms was associated with an obstructive sleep apnea genetic score. Furthermore, a type 1 diabetes genetic score was associated with a greater than average improvement of insomnia symptoms, whereas a type 2 diabetes genetic score was associated with a less than average improvement of insomnia symptoms. We compared the relative ability of demographic, genetic, and microbiome factors to explain baseline and improvement in mental health and found that genetic and microbiome factors provide value above demographic variables alone. Medication and recreational drug use do not confound microbiome associations with mental health.ConclusionsThe digital therapeutics care program significantly decreased body weight and concomitantly decreased self-reported mental health symptom intensity. Our results provide evidence that genetic and gut microbiome factors help explain interindividual differences in mental health improvement after dietary and lifestyle interventions for weight loss. Thus, individual genetic and gut microbiome factors provide a basis for designing and further personalizing dietary interventions to improve mental health.

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Section: Introductionmentioning

confidence: 99%

Mental Health Symptom Reduction Using Digital Therapeutics Care Informed by Genomic SNPs and Gut Microbiome Signatures

Pedroso¹,

Kumbhare²,

Joshi³

et al. 2022

Preprint

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“…Mendelian randomization (MR) is an increasingly used statistical method, which utilizes single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) to establish a causal relationship between an exposure and a desired outcome [15]. Instrumental variable analysis employed in MR helps simulate the randomization process of causal reasoning in randomized controlled trials (RCTs), making the design less susceptible to confounding and reverse causal bias [16].…”

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Causal relationship between gut microbiota and constipation: a two-sample Mendelian randomization study

He,

Li,

Zhang

et al. 2023

Preprint

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Background As one of the most common gastrointestinal disorders, recent study has shown that dysfunction in the gut microbiota might lead to constipation. However, the causality between the gut microbiota and constipation is unclear. Methods Genome-Wide Association Studies (GWAS) used to obtain the summary-level data of constipation through IEU OpenGWAS database, and constipation was used as outcome. In addition, MiBioGen was used to gain the summary data of gut microbiota, including Ruminiclostridium 9, Intestinibacter, Anaerotruncus, Butyricimonas and Hungatella, which were used as exposure factors. Univariable Mendelian randomization (MR) analysis was used to evaluate the causality of gut microbiota on constipation. In briefly, Inverse-variance weighted (IVW) method was regarded as a main method to estimate the causality of gut microbiota and constipation, and supplemented by other four methods, including MR-egger, Weighted median, Simple mode and Weighted mode. Finally, funnel plot, heterogeneity test, horizontal pleiotropy test and leave-one-out test were used to evaluate the reliability of MR results. Results Ruminiclostridium 9 and Intestinibacter were causally associated with constipation and were the protective factors for constipation based on the MR analysis of IVW. The causal odds ratio (OR) values of Ruminiclostridium 9 and Intestinibacter were 0.75 (95% confidence interval (CI) 0.73–0.78; P < 0.001) and 0.89 (95% CI 0.86–0.93; P < 0.001) for constipation. Moreover, Anaerotruncus, Butyricimonas and Hungatella were also causally associated with constipation but were the risk factors for constipation. The OR values of Anaerotruncus, Butyricimonas and Hungatella were 1.08 (95% CI 1.02–1.13; P = 0.007), 1.07 (95% CI 1.01–1.13; P = 0.015), 1.03 (95% CI 1.00-1.06; P = 0.037) respectively. Furthermore, validation by funnel plot, heterogeneity test and horizontal pleiotropy test showed that MR results were reliable. Conclusion Ruminiclostridium 9, Intestinibacter, Anaerotruncus, Butyricimonas and Hungatella were identified as causalities of constipation, which provided a basis for understanding pathology of constipation and new insights into prevention and treatment.

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Mental Health Symptom Reduction Using Digital Therapeutics Care Informed by Genomic SNPs and Gut Microbiome Signatures

Pedroso¹,

Kumbhare²,

Joshi³

et al. 2022

JPM

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Neuropsychiatric diseases and obesity are major components of morbidity and health care costs, with genetic, lifestyle, and gut microbiome factors linked to their etiology. Dietary and weight-loss interventions can help improve mental health, but there is conflicting evidence regarding their efficacy; and moreover, there is substantial interindividual heterogeneity that needs to be understood. We aimed to identify genetic and gut microbiome factors that explain interindividual differences in mental health improvement after a dietary and lifestyle intervention for weight loss. We recruited 369 individuals participating in Digbi Health’s personalized digital therapeutics care program and evaluated the association of 23 genetic scores, the abundance of 178 gut microbial genera, and 42 bacterial pathways with mental health. We studied the presence/absence of anxiety or depression, or sleep problems at baseline and improvement on anxiety, depression, and insomnia after losing at least 2% body weight. Participants lost on average 5.4% body weight and >95% reported improving mental health symptom intensity. There were statistically significant correlations between: (a) genetic scores with anxiety or depression at baseline, gut microbial functions with sleep problems at baseline, and (b) genetic scores and gut microbial taxa and functions with anxiety, depression, and insomnia improvement. Our results are concordant with previous findings, including the association between anxiety or depression at baseline with genetic scores for alcohol use disorder and major depressive disorder. As well, our results uncovered new associations in line with previous epidemiological literature. As evident from previous literature, we also observed associations of gut microbial signatures with mental health including short-chain fatty acids and bacterial neurotoxic metabolites specifically with depression. Our results also show that microbiome and genetic factors explain self-reported mental health status and improvement better than demographic variables independently. The genetic and microbiome factors identified in this study provide the basis for designing and personalizing dietary interventions to improve mental health.

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A Two-Sample Mendelian Randomization Analysis Investigates Associations between Gut Microbiota and Celiac Disease

Cited by 4 publications

References 20 publications

Mental Health Symptom Reduction Using Digital Therapeutics Care Informed by Genomic SNPs and Gut Microbiome Signatures

Mental Health Symptom Reduction Using Digital Therapeutics Care Informed by Genomic SNPs and Gut Microbiome Signatures

Causal relationship between gut microbiota and constipation: a two-sample Mendelian randomization study

Mental Health Symptom Reduction Using Digital Therapeutics Care Informed by Genomic SNPs and Gut Microbiome Signatures

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