EXPLORING THE LINK BETWEEN FATTY LIVER AND SIBO
Fatty Liver Disease, MASLD, and SIBO Fatty liver disease, particularly Nonalcoholic Fatty Liver Disease (NAFLD), now known as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), has become a major global health concern. In recent years, MASLD has been the second leading cause of end-stage liver disease worldwide (28). Increasing evidence reveals a fascinating connection between NAFLD and gut health, specifically a condition known as Small Intestinal Bacterial Overgrowth (SIBO). The correlation between small intestinal bacterial overgrowth (SIBO) and nonalcoholic fatty liver disease (NAFLD) has gained heightened acknowledgment, especially in the late phases of liver disease. Today, we explore the scientific links between these two conditions and why understanding this relationship matters. Understanding The Gut-Liver Axis The gut epithelium is a natural barrier that selects entry of useful substances present in the lumen, as nutrients, and keeps at bay bacteria, their bio-products and other potentially harmful elements. Tight junctions, specialized intercellular structures, assist this control. Derangement of the homeostasis between bacteria and the host, as occurs in SIBO (enhanced amount and/or changes in the type of bacteria in the gastrointestinal tract), may cause disruption of the intercellular tight junctions and subsequent increase in intestinal permeability leading to bacterial translocation (BT), i.e., transportation of bacteria and bacterial products from the intestinal lumen into the blood (4). The portal vein and the hepatic artery supply blood to the liver. The portal blood contains products of digestion and microbial products derived from the gut microbiota. This blood is carried to the liver. Therefore, Liver is the first site of exposure and filtration that consists of microbial products from the gut, such as LPS, lipopeptides, unmethylated DNA, and double-stranded RNA, which may evoke inflammatory reaction contributing to the progression of the liver disorder (4). This bidirectional relationship of the gut ecosystem and liver is imperative both physiologically and pathologically. Generally, the liver receives rich nutrients, microbial metabolites, and subproducts from the intestine and secretes bile into the small intestine (5). An integrated gut barrier also protects against toxins to maintain internal homeostasis. This gut-liver axis is regulated and stabilized by a complex network of metabolic, immune, and neurosecretory interactions between the gut, microbiota, and liver. Disruption of this equilibrium may lead to gut dysbiosis and liver injury (5). SIBO as we know is the clinical manifestation of gut microbial dysbiosis. Therefore, the bidirectional relationship between Small Intestinal bacterial overgrowth (SIBO) and fatty liver disease, particularly non-alcoholic fatty liver disease (NAFLD), is characterized by mutual influences through gut-liver axis dysfunction, inflammation, and metabolic disturbances. Association between SIBO and Fatty Liver Small intestinal bacterial overgrowth (SIBO) is a condition marked by excessive growth of microbes in the small intestine, resulting in various digestive issues including bloating, satiety, and malabsorption. In healthy people, the small bowel has a relatively low bacterial concentration, around 103–104 colony-forming units per milliliter (CFU/mL) (1,6). However, when this balance is disrupted, bacteria from the colon or oral cavity can colonize the small intestine, resulting in SIBO. Factors contributing to this condition include reduced gastric acid production, impaired intestinal motility, insufficient production of bile and dysfunction of the ileocecal valve (1,7). It may present in a range of symptoms, from moderate pain to severe nutritional deficiencies, weight loss, and shortages in crucial minerals and vitamins, including vit B12, A, D, E, iron, choline, calcium, fats, carbohydrates, protein and bile salt deconjugation (1,8). However, it has been shown that intestinal dysbiosis, endotoxemia (bacterial toxins in blood) and bacterial translocation may contribute to inflammation and Insulin Resistance (3,9,10,11,12). This directly seems to disrupt the functioning of the gut–liver axis, which may influence the incidence and progression of NAFLD (3,13). Non-alcoholic fatty liver Disease is the most frequent cause of chronic liver sickness globally, with a spectrum spanning from simple steatosis to inflammation of the hepatocytes, fibrosis, cirrhosis, and even hepatocellular carcinoma (1,14). The link between SIBO and nonalcoholic fatty liver disease (NAFLD) has attracted increased attention since studies show that the gut-liver axis plays a significant role in the pathophysiology of steatosis liver disease (1,15). The transfer of bacterial metabolites from the stomach to the liver may promote scarring and inflammation, thereby aggravating liver damage (1,16). How SIBO affects Fatty Liver? How Fatty Liver may contribute to SIBO? A growing body of evidence suggests that “altered gut microbiota” may be involved in the pathogenesis of NAFLD, via several factors (3,22,23): This bidirectional interaction exacerbates metabolic disturbances and inflammation, forming a vicious cycle contributing to disease severity as shown in the figure below (picture taken from reference 3): This picture depicts the possible SIBO and NAFLD interactions. OCTT—oro-ceacal transit time; BA—bile acids; FXR—farnesoid X receptor. Discussed below are some Clinical Studies that found a high prevalence of SIBO in NAFLD, while NAFLD increases the risk of developing SIBO. Clinical Study 1 – A cross-sectional study (1) was done to investigate the prevalence and characteristics of SIBO in patients with fatty liver disease in a tertiary healthcare facility in Karachi located in Pakistan. This study included 65 adults aged 18–80 diagnosed with NAFLD via FibroScan® and the evaluation of SIBO was established by a glucose hydrogen breath test (GHBT). The research was conducted from July 2023 to March 2024 at Ziauddin Medical University Hospital’s Clifton Campus. Results: Of the 65 individuals, 46 were male, with an average age of 44.88 ± 12.30 years, a mean index of body mass of 26.45 ± 6.45 kg/m², and an average waist measurement of 95.20 ± 15.17 cm. Lean NAFLD was observed in 40% of the participants with frequent comorbidities included – diabetes (40%), hypertension (38%), and dyslipidemia (38%). Small intestinal bacterial overgrowth was identified in 37% of the subjects, 28% of whom were asymptomatic. Symptoms prevalent in SIBO-positive individuals were bloating (41%), belching (26%), and abdominal pain (28%). Liver stiffness indicated that 23% had F2 fibrosis, 28% had F3, and 49% had F4. Controlled attenuation parameter (CAP) scores showed S1 steatosis in 37% of patients, S2 in 29%, and S3 in 34%. The presence of SIBO correlated with increasing fibrosis and steatosis
