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.

Keywords: Body mass index; Obesity; Gastrointestinal inflammation; Pathophysiology

Core Tip: Obesity has been recognized as a systemic metabolic condition and modulator of immune homeostasis. An impaired control of anti-inflammatory mediators has been associated with reduced levels of short-chain fatty acids. Some of these mediators involve interleukin (IL)-6, IL-1β and tumor necrosis factor-alpha, among others. These phenomena further perpetuate the inflammatory process all over the gastrointestinal (GI) tract. Current evidence demonstrates that higher body mass index is linked to a chronic low-grade pro-inflammatory state (“metainflammation”) and several GI-relevant processes. In this article, we review the bimolecular inflammatory processes that have an impact on the GI tract and collateral organs such as the liver.