The interplay between host genetics and the gut microbiome reveals common and distinct microbiome features for complex human diseases

Abstract

Background Interest in the interplay between host genetics and the gut microbiome in complex human diseases is increasing, with prior evidence mainly being derived from animal models. In addition, the shared and distinct microbiome features among complex human diseases remain largely unclear. Results This analysis was based on a Chinese population with 1475 participants. We estimated the SNP-based heritability, which suggested that Desulfovibrionaceae and Odoribacter had significant heritability estimates (0.456 and 0.476, respectively). We performed a microbiome genome-wide association study to identify host genetic variants associated with the gut microbiome. We then conducted bidirectional Mendelian randomization analyses to examine the potential causal associations between the gut microbiome and complex human diseases. We found that Saccharibacteria could potentially decrease the concentration of serum creatinine and increase the estimated glomerular filtration rate. On the other hand, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by host genetics, had potential causal effects on the abundance of some specific gut microbiota. For example, atrial fibrillation increased the abundance of Burkholderiales and Alcaligenaceae and decreased the abundance of Lachnobacterium, Bacteroides coprophilus, Barnesiellaceae, an undefined genus in the family Veillonellaceae and Mitsuokella. Further disease-microbiome feature analysis suggested that systemic lupus erythematosus and chronic myeloid leukaemia shared common gut microbiome features. Conclusions These results suggest that different complex human diseases share common and distinct gut microbiome features, which may help reshape our understanding of disease aetiology in humans.

Gut-Brain-Microbiota Axis: Antibiotics and Functional Gastrointestinal Disorders

“…There are many factors affecting microbiome-gut-brain-axis. These are diet, genetics, drugs, environment, exercise, cognitive behavior, stress, social interactions, and fear ( Figure 1 ) [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

Effect of a Nutritionally Balanced Diet Comprising Whole Grains and Vegetables Alone or in Combination with Probiotic Supplementation on the Gut Microbiota

“…It can possibly be used to treat and prevent osteoporosis by improving bone density through the production of vitamin K ( Fujita et al, 2012 ). In addition, low abundances of Bacteroides coprophilus in patients with multiple sclerosis and cardiac fibrillation ( Mirza et al, 2020 ; Xu et al, 2020 ) were reported in case-control studies. Indeed, the antibiotic diarrhea-prevention effects of Bacteroides fragilis ZY312 28 ( Zhang et al, 2018 ), anticancer and immune boosting effects of Bacteroides xylanisolvens DSM 23964 ( Ulsemer et al, 2016 ), and metabolic syndrome-related function of Bacteroides uniformis CECT7771 studied for use as probiotics ( Gauffin Cano et al, 2012 ).…”

Gut Microbiota–Informed Precision Nutrition in the Generally Healthy Individual: Are We There Yet?

“…Individual host genetics contribute a relatively minor portion of the variation within a person's microbiome, with lifestyle factors such as long-term diet substantially outweighing the contribution of any single nucleotide polymorphism (SNP) ( 4 ). Xu et al ( 5 ) calculated the heritability of α-diversity to be in a modest range of 3.5–10.3%; when they performed a genome-wide association study (GWAS) for enterotypes, no statistically significant signals were found. These results reflect a consensus that genetics’ impact on a person's microbiome composition is outweighed by lifestyle, geographical, and/or cultural factors ( 6 ).…”

“…However, this does not mean that host genetic variation is not a factor to consider when analyzing generally healthy individuals' microbiomes on the species level. For example, borrowing from the literature of microbiome-disease correlations where the data are plentiful, Mendelian randomization (MR) studies show that genetic predispositions to certain conditions such as chronic kidney disease have causal effects on specific bacterial species abundance ( 5 ). Such findings demonstrate the potential of leveraging large GWAS datasets such as the UK Biobank toward understanding similar host genome-microbiota dynamics in the generally healthy population.…”