Body mass index and gastrointestinal inflammation: Bio-molecular pathophysiology.

Abstract

Overweight is recognized as a worldwide healthcare problem. Obesity has increased in recent decades and has been considered a risk factor for many gastrointestinal (GI) disorders. Recent scientific evidence has documented the association between being overweight and GI manifestations. Body mass index (BMI) is a simple, globally used anthropometric measure, but its role in GI inflammation remains incompletely elucidated and can be challenging to study. Current knowledge suggests that higher BMI is linked to a chronic low-grade pro-inflammatory state ("metainflammation") and several GI-relevant processes. Obesity-related dietary patterns and "fat quality" can alter mucosal immune triggering and local inflammatory cell profiles. Increased BMI is often associated with functional GI symptoms, especially gastroesophageal reflux, likely supported by delayed oesophageal clearance, altered motility, and increased intragastric pressure. Furthermore, intestinal barrier dysfunction with dysbiosis can increase permeability and facilitate the translocation of microbial products. Metabolic endotoxemia and inflammatory pathways are triggered, including TLR4/NF-κB and the NLRP3 inflammasome. Accordingly, systemic and intestinal inflammation are developed and maintained. These mechanisms also interact with adipose tissue immune-endocrine dysregulation (increased tumor necrosis factor alpha, interleukin-6, leptin, and reduced adiponectin) and macrophage cytokine amplification, potentially affecting multiple digestive organs. Although BMI does not record fat distribution or cardiometabolic status, it can still provide clinically useful risk stratification data when interpreted alongside metabolic and functional markers. This mini-review summarizes evidence on BMI and GI inflammatory vulnerability, focusing on biomolecular pathophysiology and the main mechanisms that could explain this association.