The impact of host and environmental factors on gut microbiota variation within an average, healthy population has not been deeply studied. Two recent studies, the first one led by Dr. Jeroen Raes from the VIB Centre for the Biology of Disease/Vrije Universiteit Brussel (VUB)/KU Leuven-University of Leuven (Belgium), and the second one led by Dr. Jingyuan Fu from the University of Groningen (Netherlands), show gut microbiota variation among healthy individuals related to diet, lifestyle, and medication.
The researchers analysed faecal samples, physiological measurements and survey data from the Belgian Flemish Gut Flora Project (FGFP) (N = 1106) and the Dutch LifeLines-DEEP study (N = 1135)-the two largest cohorts of healthy volunteers explored to date. Other global datasets were also integrated, which collectively represented nearly 4,000 people (N combined = 3948), the biggest sample studied to date. “The majority of previous studies focused on specific diseases or featured a significantly smaller geographical scope,” said Dr. Raes.
The analysis identified 14-genera core gut microbes that are found in more than 95% of people, and 664 species in total. The study also reported 69 factors associated with gut microbiota composition and diversity. Most of these factors are related to stool transit time, health status, diet, medication, gender, and age. Diet stood out as an important factor, with most associations related to fibre consumption from bread and fruit. Besides this, gut microbes reveal aspects of the host’s lifestyle and health status: the researchers found associations between genus abundances and antibiotic intake (amoxicillin, for example), uric acid concentrations, stool consistency, hip circumference, and even preferred type of chocolate and beer. Stool consistency was the strongest variable associated with gut microbiota composition, whereas the factor that best explained microbial community variation among cohorts studied was the use of drugs, including antibiotics, osmotic laxatives, inflammatory bowel disease medication, female hormones, anxiolytics (benzodiazepines), antidepressants, and antihistamine. This result highlights the importance of considering drug-microbiota associations as a potential confounding factor in human microbiome studies. Regarding the association of gut microbiota composition with body mass index, the effect size was small but significant. Contrary to what was expected, mode of birth (caesarean section or vaginal delivery) and infant nutrition (breastfed or not breastfed) were not associated with adult microbiota composition variation. The study also confirmed that certain bacterial genera were associated with disease. For instance, Faecalibacterium numbers were decreased in ulcerative colitis patients and the presence of Fusobacterium was linked to colorectal cancer. More than 90% of the identified microbiota covariates in the FGFP cohort were also detected in the Dutch cohort. According to Dr. Raes, “such replication adds a tremendous amount of robustness to the results”.
The second study, led by Dr. Jingyuan Fu from the University of Groningen (Netherlands), focused on significant associations between the gut microbiota and several anthropometric, biochemical, immunological, environmental, dietary, and medication parameters and disease phenotypes in 1135 participants from the LifeLines-DEEP cohort. A total of 126 exogenous and intrinsic host factors were associated with interindividual variation of the gut microbial communities. The analysis identified negative associations between several features of a Western-style diet such as a higher intake of total energy, frequent snacking, high-fat (whole) milk and sugar-sweetened drinks, and lower microbiota diversity. Also, the use of antibiotics, proton-pump inhibitors, metformin, statins, and laxatives had a strong effect on the gut microbiota.
Whereas these factors collectively accounted for 18.7% of microbial community variation, faecal chromogranin A (CgA)—a protein secreted by enteroendocrine cells that is thought to be involved in stress situations and active periods of gut-related diseases—was exclusively associated with 61 microbial species whose abundances collectively explained 53% of the total abundance of the gut microbial composition. Low CgA concentrations were associated with higher microbiota diversity, functional richness, high concentrations of high-density lipoprotein (HDL) and high intake of fruits and vegetables. These results suggest that faecal levels of CgA could be used as a potential biomarker for gut health, whereas other factors assessed only exerted a very modest effect. Further studies are needed in order to explore the causality and underlying mechanisms of these observations.
In conclusion, these data provide new insights regarding the impact of host and lifestyle factors on gut microbiota variation across healthy individuals. These results provide important information for future disease research and clinical studies: it may be appropriate to include the identified covariates (dietary information, lifestyle, health status, anthropometrics, transit time, medication) in future clinical studies. However, follow-up studies with an even bigger sample size are needed in order to continue exploring the overall gut microbiota biodiversity and identifying other factors that contribute to microbiota compositional variation.
Falony G, Joossens M, Vieira-Silva S, et al. Population-level analysis of gut microbiome variation. Science. 2016; 352(6285):560-4.
Zhernakova A, Kurilshikov A, Bonder MJ, et al. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science. 2016; 352(6285):565-9.
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