The global rise in obesity rates has become a pressing economic and health issue, with its prevalence linked to a range of serious health conditions, including cardiovascular diseases, diabetes and various cancers. Recognised as a multi-factorial disorder, obesity's causes are complex, involving genetics, environment, behaviour and psychology. Among the environmental factors, the gut microbiome has emerged as a significant contributor to its onset.
Comprising approximately 100 trillion species, the gut microbiota plays a crucial role in maintaining intestinal function and metabolic health. Alterations in the gut microbiota have been shown to contribute significantly to the development of metabolic disorders such as obesity. While genetics do play a role in shaping the gut microbiota, environmental factors, particularly diet, exert greater influence.
Recent research has provided evidence of a causal relationship between the gut microbiota and obesity. Studies involving the transplantation of gut microbiota from normal mice to germ-free mice have resulted in increased body fat percentage, independent of changes in food intake. Other studies have identified specific microbial species that may have protective effects against obesity.
Researchers have proposed several mechanisms to explain the link between the gut microbiota and obesity. These include the gut microbial community's ability to enhance energy intake from food, the modulation of lipid and glucose metabolism through the production of short-chain fatty acids (SCFAs), and the influence of gut microbiota on the production of hormones involved in appetite regulation.
In an effort to better understand the role of gut microbiota in obesity, researchers have conducted studies analysing the gut microbiota characteristics of individuals with different types of obesity. By exploring these characteristics, researchers aim to gain insights into the pathogenesis of obesity and identify potential therapeutic targets for obese individuals.
Mustering the guts to address obesity
Researchers at The First Hospital of Jilin University in China recently conducted a meta-analysis by employing the Mendelian randomisation analysis method (a method used to infer causality in observational studies using genetic variants as instrumental variable) has revealed a significant link between gut microbiota characteristics and various obesity sub-types in order to shed light on potential avenues for novel obesity treatments.
The researchers obtained whole-genome association study data on gut microbiota from the FinnGen research project and International MiBioGen Consortium, which had coordinated 16S rRNA gene sequencing profiles and genetic typing data for 18,340 participants in the US, Canada, Israel, South Korea, Germany, Denmark, the Netherlands, Belgium, Sweden, Finland and the UK to investigate the gut microbiota profiles of obese individuals, aiming to uncover underlying mechanisms driving different types of obesity.
After rigorous analysis, the study established a link between the composition of gut microbiota and obesity by identifying potential several microbial communities that appeared to influence the onset of obesity-related conditions.
For example, Ruminococcaceae UCG010 was found to independently reduce the risk of obesity from excess calorie intake, while Butyricimonas was associated with increased obesity risk in the same context. Additionally, Pasteurellaceae was identified as a protective factor for localised adiposity and Lactobacillus was found to reduce the risk of extreme obesity with alveolar hypoventilation.
Furthermore, the study identified several other microbial communities that could play a role in the development of obesity-related conditions, such as drug-induced obesity. These include the Ruminococcus torques group, Desulfovibrio and Catenabacterium, among others.
The future of fat-fighting
Despite the significant advancements provided by the study, the researchers acknowledged certain limitations, including the focus on European populations and potential oversight of gut microbiota beyond the scope of existing databases.
Importantly, the researchers conducted sensitivity analyses to ensure the robustness of their findings, including tests for heterogeneity and pleiotropy among the genetic variants studied. While previous research had demonstrated the impact of gut microbiota on obesity, this study provided novel insights by identifying specific bacterial species associated with different obesity sub-types, offering potential targets for future obesity management strategies.
They concluded: “There is a causal relationship between gut microbiota abundance and obesity, with distinct gut microbiota profiles observed in different obese populations. The bacteria independently influence the development of various types of obesity. Additionally, there are six gut microbiota species with potential associations with the development of obesity. The adjunctive therapy of probiotics and prebiotics may emerge as a novel approach in the future treatment of obesity.
Source: Frontiers
“Unraveling the mystery: a Mendelian randomized exploration of gut microbiota and different types of obesity”
https://doi.org/10.3389/fcimb.2024.1352109
Authors: Siyuan Liu, et al.
