Protocol for a pilot multi-centre, randomized controlled trial of the effect of inulin on gastrointestinal microbiota outcomes in mechanically ventilated adults: the INTESTINAL trial

Background Critical illness results in dysbiosis defined as a reduction in diversity of commensals and colonisation with pathogenic bacteria. Dysbiosis is associated with acute and chronic inflammatory response and immune dysregulation. The gastrointestinal microbiome has a well-established immunomodulatory role via various pathways including production of short chain fatty acids (SCFAs). Non-digestible dietary fibres, such as inulin can modulate the gastrointestinal microbiome and increase SCFA production with potentially favourable inflammatory and immune outcomes. Methods This is a two-centre, randomised, placebo-controlled, pilot trial to assess the ability of dietary inulin to enhance SCFA-producing taxa in critically ill mechanically ventilated patients. Participants will be randomised during their admission to the Intensive Care Unit (ICU) to the intervention dietary inulin (10 grams once daily) or placebo (water for ingestion), in addition to standard enteral nutrition. The intervention/placebo will be administered for a maximum of 7 days while in ICU. The primary outcome will be assessment of diversity of gastrointestinal microbiota. Secondary outcomes will be feasibility and process of care. An immunological sub-study will assess T-regulatory cell function and innate immune cell phagocytic function. Discussion Although inulin promotes bifidogenesis in healthy people, evidence in critical illness is limited. The INTESTINAL pilot will study short-term inulin effects on gut microbiota and immune markers in acutely ill ventilated patients, generating novel mechanistic data to inform future, larger outcome-focused trials. Ethics and dissemination All study procedures will be integrated into usual care of critically ill patients, and no new interventions other than inulin are required. Dietary inulin is a safe and well tolerated dietary fibre with only minor gastrointestinal adverse effects reported. The results of this trial will be published in a peer-reviewed journal. Trial Registration Australian and New Zealand Clinical Trials Registry number: ACTRN12625000319471.