Gut microbiome and obesity: what we know - and what we don’t

The obese microbiome

The gut microbiome has evolved in symbiosis with humans. However, it has not fully adapted to the rapid environmental and dietary changes experienced since the time of hunter-gatherers. Predicted gut microbiome composition in these populations resembles that observed in modern isolated groups in Africa, Australia, New Zealand, and other populations with limited exposure to Western diets. Although several bacterial taxonomic groups and microbiome patterns, known as enterotypes, have been associated with healthy and sick populations, the combination of parameters that identify who is present and what they do is crucial. 

Parameters commonly used to describe gut microbiome composition include taxonomic diversity, the presence of specific bacterial groups often labeled as “beneficial”, and the balance between major phyla. These measurements typically emphasize higher diversity, greater representation of Bacteroidetes, Prevotella, and Actinobacteria such as Bifidobacteria, and a higher Bacteroidetes to Firmicutes ratio. In contrast, parameters that better reflect host microbiome interactions focus on functionality rather than composition alone. High diversity does not necessarily indicate functional health; enzymatic activity and metabolic output are more informative. These include the production of health-associated metabolites such as short-chain fatty acids, branched-chain amino acids, and butyrate, as well as correlations between specific microbial strains and physiological states, such as methane or glutamate production. Additional functional markers include inflammatory status and the microbiome’s resilience, defined as its ability to return to baseline after disruption.

These parameters have influenced our understanding of gut microbiome composition and functionality since early research in mice. They have enriched current knowledge of associations between the gut microbiome and the development of pathologies. One of the most researched topics is obesity, and while its pathophysiology is still under review, theories have focused on evolutionary energy-saving phenotypes, obesity prone genes, climate-related adaptations, metainflammation, and neuroendocrine pathways. Together, these theories position the microbiota as a central influencer on host metabolism and, potentially, genetic expression. 

The taxonomic signature of obesity has been described as decreased bacterial diversity, reduced gene richness, and a low Bacteroidetes to Firmicutes ratio. However, this pattern has not been consistently observed among populations living with obesity, suggesting substantial functional redundancy that requires further investigation. Improving bacterial characterization at lower taxonomic ranks, particularly at the strain level, alongside metabolomic analyses, is essential to better understand which bioactive factors are most relevant to obesity. For example, Bacteroides thetaiotaomicron, present at low abundance in some individuals with obesity, has been associated with increased bacterial glutamate production, suggesting that microbial strains and their metabolites may influence the physiology of obesity and its treatment.

Nevertheless, questions remain regarding how these biological concepts and parameters should guide medical practice, particularly as the availability of microbiome tests, probiotics, and prebiotics continues to grow. The international consensus statement on microbiome testing in clinical practice outlines 31 expert agreements, highlighting several key issues: clear communication regarding the limited evidence for clinical application; lack of laboratory standardization in sample processing; lack of consensus on laboratory reporting; discouragement of dysbiosis indices and metabolomic analyses in routine practice; avoidance of clinical inferences based solely on composition or metabolic profiles; discouragement of direct patient initiated testing requests; and the absence of formal postgraduate training programs in microbiome science for clinicians.

There is still a long way to go regarding public microbiome testing. Nevertheless, the widespread availability of information has fueled speculation about the gut microbiome’s role in overall health. Aided by the growing acceptance and production of prebiotics and probiotics, international organizations are encouraging self-education while simultaneously developing clinical guidelines that emphasize caution across disease contexts. The World Health Organization notes regarding over-the-counter biotics that “there is no evidence from comparative studies to rank products in terms of efficacy. The tables do not provide grades of recommendation, but only levels of evidence according to evidence-based medicine criteria.” 

Management and Intervention

In obesity management, the triad of nutritional, pharmacological, and surgical interventions is the standard of care. Only nutritional interventions are opening the possibility to microbiome modulation by including fermented foods, which are frequently highlighted as a natural approach to modulating the gut microbiome. Foods such as yogurt, kefir, fermented vegetables, and traditional fermented products contain live microorganisms, and their fermentation-derived metabolites may transiently influence microbial activity. However, evidence supporting a specific role for fermented foods in obesity management remains limited and highly context dependent. Rather than acting as targeted microbiome interventions, fermented foods are better understood as contributors to overall dietary quality and diversity. As with other dietary components, their effects on metabolic health likely depend on the broader dietary context, individual host factors, and baseline microbiome composition.

In addition, specific prebiotics that support the production of beneficial metabolites are contemplated among the nutritional interventions in obesity care. Aiming at a community effect rather than a strain-specific strategy, the use of fructans, fructooligosaccharides (FOS), and galactooligosaccharides (GOS) present in milk, fruits, vegetables, and supplements hopes to affect Bifidobacteria and Lactobacili populations to produce health benefits in the host. It is worth mentioning that dietary choices impact the microbiome differently at individual and population levels; microbiome science is still trying to define how different eating patterns and food products affect it.

Regarding probiotics, certain microorganisms have been associated with lean phenotypes, improved intestinal barrier function, and enhanced glucose tolerance, primarily through studies targeting specific bacterial genera (Lactobacillus, Bifidobacterium) and yeasts (Saccharomyces). However, supplementation requires further standardization, clinical validation, safety assessment, and evaluation of long-term effects. Until then, clinicians should not fall under the dietary supplementation premise and be aware of what to look for when recommending or evaluating these products. Labels should clearly state taxonomic identification (genus, species, and strain), viable counts at the end of shelf life, specific health claims associated with the strain, and dosages supported by physiological evidence. This information is essential to ensure product traceability and reproducibility of effects. To date, discrepancies between label claims and actual microbial content have been documented in some commercial products.

In summary, microbiome science is advancing at an extraordinary pace. With the integration of artificial intelligence and the refinement of the -omics methods, metadata will continue to expand, and new disease associations will inevitably emerge. To date, there is no validated bacterial strain-based treatment for obesity, despite the description of multiple mechanistic associations involving taxa such as Bifidobacterium and Akkermansia. However, as data grows, research is focusing on developing reproducible mechanisms to generate clinically actionable steps and on the ethical implementation of testing and supplementation. This creates a window of opportunity for a stronger dialogue between researchers and clinicians that can lead microbiome science into clinical practice. For now, personalized nutritional and lifestyle interventions that support metabolic and gut health are the most practical approach.