Microbiota intestinal como potencial marcador pronóstico de respuesta a la cirugía bariátrica en pacientes con obesidad patológica

Abstract

Introduction Obesity is a global epidemic affecting more than 650 million people, according to the World Health Organization. This chronic disorder is associated with various comorbidities such as type 2 diabetes, cardiovascular diseases, and non-alcoholic fatty liver disease. Bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB), has proven to be an effective intervention for the treatment of morbid obesity, not only due to the significant weight loss it induces but also for its ability to improve or resolve associated comorbidities. However, the variability in patients' response to this intervention has highlighted the need to better understand the underlying factors contributing to the success or failure of the surgery. The gut microbiota, a complex microbial ecosystem that plays a crucial role in metabolism regulation, has emerged as a possible mediator of these outcomes. This doctoral thesis focuses on investigating how the composition and changes in the gut microbiota can predict and affect the results of bariatric surgery. Objectives: The aim is to evaluate the relationship between the percentage of total weight lost (%TWL) and changes in the microbiota, to determine the evolution of key bacterial species after surgery, and to explore the initial microbiota composition as a predictor of clinical outcomes. Materials and Methods The study was conducted on a cohort of 120 morbidly obese patients undergoing RYGB, with a 12-month postoperative follow-up. Fecal samples and clinical data were collected both preoperatively and 12 months postoperatively. 16S rRNA gene sequencing was used to analyze the composition of the gut microbiota. Statistical analyses included correlation tests and regression models to assess the relationship between the microbiota and clinical outcomes. Results The results indicate that patients who achieved a %TWL greater than 34.2% had a higher microbial richness at baseline and showed significant changes in their microbiota composition after surgery. Bacterial species such as Akkermansia muciniphila and Roseburia inulinivorans were more abundant in patients with greater weight loss success, while Bacteroides fragilis and Ruminococcus gnavus were more common in those with lesser weight loss. These findings suggest that the initial composition of the microbiota could influence the metabolic response to bariatric surgery. Conclusions The analysis of the gut microbiota before and after surgery reveals that certain bacterial species may be associated with a better or worse prognosis in terms of weight loss. The greater abundance of anti-inflammatory and metabolism-promoting species, such as Akkermansia muciniphila, in patients with greater weight loss reinforces the hypothesis that the microbiota plays a central role in mediating the effects of bariatric surgery. On the other hand, the presence of bacteria associated with chronic inflammation, such as Ruminococcus gnavus, may be related to the reduced effectiveness of the surgery in some patients. The gut microbiota emerges as a crucial factor in the variability of bariatric surgery outcomes. Changes in its composition after the intervention and the initial microbial composition could serve as key indicators to predict success in terms of weight loss and resolution of comorbidities. These findings underscore the importance of considering the gut microbiota in the design of personalized therapeutic strategies for managing obesity. Future studies could focus on modulating the microbiota to improve postoperative outcomes in patients undergoing bariatric surgery.