Effect, tolerability, and safety of exclusive palatable elemental diet in patients with intestinal microbial overgrowth

Elemental diets (EDs) have desirable safety and efficacy profiles in several clinical settings partly due to modulation of gut microbiome. Palatability of EDs remains the main barrier to compliance/adherence, and their effect has not been prospectively explored in microbiome-driven disorders such as small intestinal bacterial overgrowth (SIBO) and intestinal methanogen overgrowth (IMO). We aimed to assess the effect, tolerance, and safety of a novel palatable ED (PED) in subjects with IMO and/or SIBO. Adult subjects with positive lactulose breath tests (LBT) for SIBO and/or IMO completed one week of screening, 2 weeks of exclusive oral PED, and 2 weeks of follow-up during reintroduction of regular diet. Primary endpoint was changes in stool microbiome after PED and reintroduction of regular diet. Secondary endpoints included tolerability, rate of normalization of LBT, change in stool form based on daily diary and artificial intelligence-analyzed images, symptomatic response, and adverse events. All 30 enrolled subjects tolerated the PED and completed the trial. Several taxonomic differences were detected including decreased relative abundance of Prevotella_9 and Fusobacterium. Abundance of Methanobrevibacter smithii decreased at the end of the trial and correlated with average daily methane levels (p=0.024, r=0.489). Maximum methane levels (41±35 to 12±15 ppm, p<0.001) and hydrogen rise (43±42 to 12±11 ppm, p<0.001) dropped significantly, with 73% normalizing their LBT. Adequate global relief of symptoms was reported in 83% of subjects. No serious or severe adverse events were observed. PED significantly impacts the gut microbiome. Tolerance to EDs improve with enhanced palatability. Larger studies with longer follow-up are needed to assess response durability. (ClinicalTrials.gov ID: NCT05978973).