Bidirectional interplay between gut and liver in inflammatory bowel disease and hepatobiliary conditions

Inflammatory bowel disease (IBD) can affect extraintestinal organs, including the liver. The bidirectional relationship between the gut and liver underpins the interplay between IBD and liver pathologies; both are predicted to rise. This review discusses the anatomical-physiological context of the gut-liver axis, the influence of IBD on the liver and vice versa, and hepatobiliary conditions co-existing with IBD, namely, MASLD, ARLD, PSC and gallstones. About 70% of the liver’s blood supply comes from the gut via the portal vein, which carries both nutrients and gut-derived microbial products, as regulated by the intestinal barrier. IBD is associated with gut dysbiosis and compromised intestinal barrier integrity (both exacerbated by alcohol consumption, an IBD risk factor), allowing microbial translocation to the liver, which triggers hepatic inflammation/injury. This exacerbates pre-existing liver disease or increases its risk; for example, IBD increases MASLD risk. However, translocated lipopolysaccharides may alleviate cholestatic liver injury, enabling IBD to ameliorate PSC. In turn, PSC can promote a favourable gut microbiota profile to alleviate IBD. The liver maintains gut homeostasis/microbiota through bile acid secretion. Disrupted bile acid secretion in gallstones increases IBD risk, while disrupted bile acid reabsorption in IBD increases gallstone risk. Disrupted bile acid metabolism and an abnormal gut microbiota in MASLD may exacerbate the IBD course. For co-existing IBD-hepatobiliary pathology, management strategies are unestablished, and adverse effects of IBD therapeutics on hepatobiliary pathologies are observed (and vice versa). This review facilitates a structured understanding of the pathophysiological connections and may inform/improve the current management of coexisting IBD-hepatobiliary conditions.