Chinese scientists used data from multiple independent large-scale genome-wide association studies (GWAS) on gut microbiota and longevity to examine the genetic correlation and potential causal association between gut microbiota and longevity.
They performed linkage disequilibrium score (LDSC) regression and Mendelian Randomisation (MR) analyses and note genetic correlations between four bacterial species and three (GWAS) aging traits (paternal longevity or parental life or health span).
Writing in BMC Microbiology, study authors explain the role of gut microbiota in parental longevity, in helping modulate chronic metabolic disease, immune function, and observable characteristics of aging.
“As metabolic diseases and aging are both characterised by low-grade inflammation and activation of the innate immune system, the influence of gut microbiota on obesity and related metabolic disorders may help detect healthy aging.”
They point out that longevity “reversely” influences gut microbiota due to the abundance of antibiotic resistance genes (ARG) and age-related changes to gut composition and structure.
“The longevity process has been shown to have a profound effect on the composition and structure of gut microbiota by regulating host metabolisms, such as lactobacillus intake and defecation frequency.”
However, studies indicate a positive association between microbial metabolic markers and gut microbiome uniqueness, “reflecting a healthy aging phenotype and predicting longevity of older adults”.
“Our results hope to provide biomarkers for clinicians and researchers to assess aging status by detecting changes in gut microbiota,” they assert.
Genetic risk variants
Data demonstrated the positive influence of Collinsella, Roseburia, and Sporobacter on longevity and healthy aging, as well as negative outcomes associated with Veillonella.
Roseburia produce’s beneficial SCFAs, such as butyrate, which enhance gut immune and anti-inflammatory activity, leading to improved health outcomes in chronic conditions, such as atherosclerosis and alcoholic fatty liver, the authors’ write.
“Imhann et al. emphasised the importance of considering the interaction of gut microbiota and host genes as they relate to immune system function, with a higher number inflammatory bowel disease (IBD) genetic risk variants associated with a decrease in the abundance of Roseburia.”
However, microbiota may also be a pathogenic factor in disease progression, such as colorectal cancer, cystic fibrosis, and ulcerative colitis, associated with Veillonella. In the current study, the bacterium was found in increased abundance among patients with early gastric cancer.
Results confirm the strong influence of dietary factors on gut pathology. For example, Collinsella abundance is especially associated with the Mediterranean diet and can reduce incidence of chronic metabolic disease and cancer. In the current study, levels were significantly higher in South Korean centenarians.
“Notably, although Collinsella has recently been associated with metabolic regulation, atherosclerosis, and type 2 diabetes mellitus, dietary interventions strongly influence Collinsella,” the authors’ comment.
On the other hand, Sporobacter (part of the Ruminococcaceae family) encourages production of short-chain fatty acids (SCFAs) that regulate appetite, energy metabolism, inflammation, and disease. It also helps control intestinal infection and low levels have been linked to ulcerative colitis (UC), multiple sclerosis (MS), rheumatoid arthritis (RA), and Crohn’s disease (CD).
“We speculated that the genetic association between Sporobacter and longevity might be due to their shared influence on immune function and immune-mediated inflammatory diseases,” the authors explain.
Overall, the observed causal associations may potentially provide “novel clues for the genetic pathogenies of the effect of gut microbiota on longevity”, they add.
Source: BMC Microbiology
Published online, December 13, 2022: http://doi.org/10.1186/s12866-022-02703-x
‘Association between gut microbiota and longevity: a genetic correlation and Mendelian randomisation study’
Authors: Dan He, Li Liu, Zhen Zhang, Xuena Yang, Yumeng Jia, Yan Wen, Shiqiang Cheng, Peilin Meng, Chun’e Li, Huijie Zhang, Chuyu Pan and Feng Zhang