PWE-055 Iron supplementation, microbiome related methanogenesis and constipation – novel model to explain an age-old problem

Introduction Oral iron supplementation is given in a broad range of conditions such as iron-deficiency anaemia but can cause significant gastrointestinal side effects in up to 70% of patients. Constipation and bloating are amongst the commonest side effects. Recent research has shown that increased methane production by archaea in the gut microbiome is related to the slowing of gut transit and constipation, via inhibition of smooth muscle contractility (1). Geobiological research has shown that iron is the most abundantly required metal in the archaeal enzymatic pathway for methanogenesis (2). We hypothesized that oral iron consumption resulted in increased methane production. Methods A retrospective study of 396 patients who attended The Functional Gut Clinic for a lactulose or glucose hydrogen and methane breath test between June 2018 and January 2019 was carried out. Prior to the test, patients followed a 24hr low fermentable diet and 12hr fast. After providing a baseline breath sample, 10g lactulose or 75g glucose was ingested with 200mL water. Breath samples were taken every 15-minute for 135 minutes. Methane was detected using a sensitive gas chromatography technique and methane producers defined as those producing ≥10ppm at any point during the study. The relationship between iron supplementation and the prevalence of breath methane was analysed via a Chi-squared test and cumulative methane production was analysed via a two-tailed T-test. Due to lack of information about iron supplementation, 59 patients were excluded. Results Of the patients that took iron supplements, 32% produced methane, versus 17.5% of non-iron takers. A significant relationship was identified between iron supplementation and breath methane χ(1, N=337)=4.3885, p Conclusions This preliminary, observational study provides the basis for a new model linking a dietary intervention (ingestion of oral iron supplementation) to a gut microbiome metabolic process (methanogenesis) and a clinical outcome (constipation) which is a common, unexplained side effect of the intervention. This model can be used in prospective studies to determine risk factors for developing GI side effects and test potential therapeutic interventions aimed at disrupting methanogenesis and improving tolerability. These advances would have significant clinical and cost saving potential in a broad group of patients. References Pimentel, M, et al. -Am J Physiol Gastrointest Liver Physiol 2006:290 Goswani, R, et al. - Biotech, 2016: 6:72