What does irritable bowel syndrome share with non-alcoholic fatty liver disease?

Abstract

Non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS) are two very common diseases in the general population. To date, there are no studies that highlight a direct link between NAFLD and IBS, but some recent reports have found an interesting correlation between obesity and IBS. A systematic PubMed database search was conducted highlighting that common mechanisms are involved in many of the local and systemic manifestations of NAFLD, leading to an increased cardiovascular risk, and IBS, leading to microbial dysbiosis, impaired intestinal barrier and altered intestinal motility. It is not known when considering local and systemic inflammation/immune system activation, which one has greater importance in NAFLD and IBS pathogenesis. Also, the nervous system is implicated. In fact, inflammation participates in the development of mood disorders, such as anxiety and depression, characteristics of obesity and consequently of NAFLD and, on the other hand, in intestinal hypersensitivity and dysmotility.

HMGB1-RAGE pathway drives peroxynitrite signaling-induced IBD-like inflammation in murine nonalcoholic fatty liver disease

“…Interestingly, there are considerable reports of circulatory cytokines, lack of adiponectin or increased leptin in NAFLD that are proinflammatory in nature but a direct mechanistic link to colonic inflammation is scarce [28]. Our observation that high circulatory HMGB1 in absence of significant other organ injuries probably originates in the damaged liver bodes well for a prominent role of this DAMP in causing ectopic intestinal inflammation.…”

β-Klotho gene variation is associated with liver damage in children with NAFLD

“…[25][26][27][28] Recently, two functional genetic variants modulating the activity of the KLB/FGFR4 pathway, namely rs17618244 G>A KLB and rs1966265 G>A FGFR4, encoding for the R728Q and V10I aminoacidic substitutions have been associated with accelerated transit in irritable bowel syndrome, 29 supporting a possible functional impact on the regulation of the gut-liver axis via modulation of FGF19 signaling. 30 Therefore, the aim of this study was to examine the impact of the rs17618244 G>A KLB and rs1966265 G>A FGFR4 variants on liver damage severity in pediatric patients with NAFLD.…”

Depressionen und Lebererkrankungen: Die Rolle von Mikrobiom und Inflammation

“…Eine weitere wegweisende Studie weist dabei auf eine bedeutsame Beteiligung der Darmbakterien und Mikroben hin. Werden Mikroorganismen aus dem Darm, sogenannte Mikrobiota, von depressiven Patienten durch orale Gabe auf nichtdepressive Versuchstiere übertragen, entwickeln diese ebenfalls depressive Verhaltensmuster [51,52], während Mikrobiota von gesunden Probanden keinen entsprechenden Effekt auslösten [51]. Möglicherweise könnte das Mikrobiom, die Gesamtheit aller Mikroorganismen, die den Darm besiedeln, das Bindeglied zwischen Depressionen und Lebererkrankungen sein [52].…”

“…Werden Mikroorganismen aus dem Darm, sogenannte Mikrobiota, von depressiven Patienten durch orale Gabe auf nichtdepressive Versuchstiere übertragen, entwickeln diese ebenfalls depressive Verhaltensmuster [51,52], während Mikrobiota von gesunden Probanden keinen entsprechenden Effekt auslösten [51]. Möglicherweise könnte das Mikrobiom, die Gesamtheit aller Mikroorganismen, die den Darm besiedeln, das Bindeglied zwischen Depressionen und Lebererkrankungen sein [52]. Großangelegte Studien zur Mikrobiotabesiedelung bei depressiven Patienten stehen zwar noch aus, erste Ergebnisse mittels DNA-Sequenzierung weisen aber darauf hin, dass das Gleichgewicht des Mikrobioms bei einer Vielzahl von Erkrankungen gestört ist, auch bei Depressionen [53][54][55][56] und Lebererkrankungen [57][58][59].…”