Revolutionising obesity treatment with new gender-specific microbiome findings
Recent investigations to be unveiled at the European Congress on Obesity (ECO) held in Venice, Italy, from the 12th to the 15th of May, 2024, have shed light on the pivotal role that variations in gut microbiota composition play in the genesis and evolution of obesity, revealing notable distinctions between genders. This differentiation may significantly influence the metabolism of various nutrients, thereby affecting the presence of bioactive molecules within the gut that are crucial in the progression of metabolic diseases.
The gut microbiota encompasses a complex consortium of microorganisms, including bacteria, viruses, fungi, and protozoa, that reside within the gastrointestinal tract. A state of imbalance within this microbial community, known as dysbiosis, has profound effects on metabolic health, altering the risk of developing diseases such as obesity. Yet, the specific microbial species that contribute to a higher or lower risk of obesity and their exact impact on metabolic health remain subjects of ongoing research.
In an effort to deepen understanding of the role these microorganisms play in obesity, researchers conducted an analysis of metagenomic and metabolomic data from a Spanish cohort. This analysis aimed to decipher the mechanisms through which gut microbes contribute to obesity’s development.
The study involved examining the faecal metabolome—the vast array of metabolites found in the gut and excreted in faeces, produced by gut bacteria as they metabolise food. These metabolites enter the bloodstream, where they can have significant health impacts.
A total of 361 adults (251 women and 110 men, with a median age of 44 years) from the Spanish Obekit study—a randomised trial exploring the relationship between genetic variants and responses to a hypocaloric diet—were included in the analysis. Participants were categorised based on their obesity (OB) index into LOW (BMI ≤ 30 kg/m²; fat mass percentage ≤ 25% for women or ≤ 32% for men; waist circumference ≤ 88 cm for women or ≤ 102 cm for men) or HIGH (BMI > 30 kg/m²; fat mass > 25% for women or > 32% for men; waist circumference > 88 cm for women or > 102 cm for men) obesity levels. This grouping ensured a balanced representation of sexes and ages within each category.
Microbiota profiling through genetic analysis was employed to ascertain the diversity, composition, and relative abundance of bacteria in participants’ stool samples.
Key findings indicated that individuals with a HIGH OB index displayed significantly reduced levels of Christensenella minuta—a bacterium associated with leanness and health. In men, an increased presence of Parabacteroides helcogenes and Campylobacter canadensis was strongly linked to elevated BMI, fat mass, and waist circumference. Conversely, in women, a higher abundance of Prevotella micans, Prevotella brevis, and Prevotella sacharolitica was strongly indicative of increased BMI, fat mass, and waist circumference, but these associations were not observed in men.
Further analyses, examining a broader spectrum of metabolic compounds in the blood, identified variations in certain metabolites, particularly elevated levels of bioactive lipids—phospholipids and sphingolipids—which are implicated in metabolic disease development and are key modulators of insulin sensitivity and contributors to diabetes and vascular complications in individuals with a HIGH OB index.
Dr. Paula Aranaz, the study’s lead author from the Centre for Nutrition Research at the University of Navarra in Spain, explained, “Our findings underscore the significant role of bacterial imbalance in the onset and progression of obesity, highlighting notable differences between genders. This imbalance affects the metabolism of bioactive molecules in the metabolome, which in turn influences metabolic disease development.”
Dr. Aranaz further elaborated on the protective role of the Christensenella minuta bacterium against obesity and noted that the microbial species influencing obesity risk differ by sex. This necessitates gender-specific interventions to prevent an obesity-promoting microbiome. She emphasised the need for additional research to pinpoint when the shift to an obesity-favourable gut microbiota occurs, to better time potential interventions.
She concluded with optimism, stating, “This study demonstrates the utility of combining metagenomics with metabolomics to unravel the mechanisms at play in metabolic disease development, such as obesity. This innovative, comprehensive approach has the potential to foster the creation of nutritionally precise strategies for weight management that alter specific bacterial strains or bioactive molecule levels.”
However, the authors acknowledged certain limitations of their study, including its relatively small sample size—particularly for men—and its geographical limitation to one region in Spain. Given that factors such as climate, geography, diet, and culture can influence the gut microbiome, the applicability of these findings to other populations may be limited.