Body mass index and gastrointestinal inflammation: Bio-molecular pathophysiology

Figure 1 Schematic representation of gastrointestinal inflammation as a central correlation in obesity-associated metabolic dysregulation. Chronic positive energy balance leads to increased body mass index and excessive adiposity, which are associated with alterations in gut microbiota (dysbiosis) and increased intestinal permeability. These changes encourage translocation of microbial products and triggering of local and systemic immune responses, resulting in low-grade chronic inflammation. The digestive tract is instrumental in the development of metabolic syndrome and gastrointestinal symptoms, reinforcing systemic metabolic dysfunction. This interconnected network highlights the gastrointestinal tract as a key interface among environmental, metabolic, and immune factors involved in the pathophysiology of overweight and obesity-related chronic diseases. GI: Gastrointestinal; BMI: Body mass index.

Figure 2 Dietary patterns and influence on gastrointestinal inflammation. Healthy dietary patterns, such as the Mediterranean diet, suppress inflammatory cascades. Unhealthy dietary patterns, such as the Western diet, increase macrophage activity and promote intestinal inflammation. GI: Gastrointestinal.

Figure 3 Excess adiposity and Intestinal barrier dysfunction represents an immune–metabolic imbalance driven by excess adipose tissue. Chronic low-grade inflammation marked by increased tumor necrosis factor alpha, interleukin 6, interleukin-1, resistin, and leptin, and reduced adiponectin, triggers key inflammatory pathways (NF-κB, TLR4, NLRP3), promoting meta-inflammation. TNF-α: Tumor necrosis factor alpha; IL: Interleukin 6; NF-κB: Nuclear factor kappa B; TLR4: Toll-like receptor 4; NLRP3: NOD-like receptor family pyrin domain containing 3; LPS: Lipopolysaccharides; CF: Cystic fibrosis; AMPs: Antimicrobial peptides.

Figure 4 Dysbiosis–endotoxemia–inflammation–barrier dysfunction cycle induced by a high-fat diet. Obesity-associated dysbiosis stimulates lipopolysaccharides translocation and tumor necrosis factor alpha/nuclear factor kappa B triggering, with ↓zonula occludens-1, ↑paracellular permeability, and ↓mucin production. At the same time, ↓NOD-like receptor family pyrin domain containing 6-interleukin-18 signaling and ↓aryl hydrocarbon receptor activity damage mucosal integrity, and reduced ethanolamine availability (a phosphatidylethanolamine precursor) may contribute to ↓phospholipid synthesis, increasing epithelial disruption. AHR: Aryl hydrocarbon receptor; IL: Interleukin; LPS: Lipopolysaccharides; NF-κB: Nuclear factor kappa B; TNF-α: Tumor necrosis factor alpha; ZO-1: Zonula occludens-1; NLRP6: NOD-like receptor family pyrin domain containing 6.

Figure 5 Self-amplifying cycle of chronic inflammation in obese adipose tissue. Obese adipocytes, undergoing endoplasmic reticulum stress and NOD-like receptor family pyrin domain containing 3 inflammasome triggering, release pro-inflammatory cytokines [tumour necrosis factor alpha, interleukin (IL)-6, IL-1β, IL-18] and recruit M1 macrophages via monocyte chemoattractant protein-1. Infiltrating M1 macrophages also trigger their inflammasomes and secrete additional cytokines, establishing a continuous feedback loop that maintains tissue inflammation. ER: Endoplasmic reticulum; NLRP3: NOD-like receptor family pyrin domain containing 3; TNF-α: Tumour necrosis factor alpha; IL: Interleukin; MCP-1: Monocyte chemoattractant protein-1; CCL2: C–C motif chemokine ligand 2; M1: Classically activated (pro-inflammatory) macrophage phenotype.