Anne Karmisholt Grosen

Background: Clostridioides difficile infection (CDI) is a major cause of hospital-acquired infections. Faecal microbiota transplantation (FMT) is a safe and effective treatment to prevent CDI recurrence, but treatment efficiency depends on patient and donor characteristics. To investigate how donor microbiome and metabolite profiles are associated with FMT treatment efficiency in patients with CDI, data from a Danish cohort where faeces samples were collected from 47 donors and 102 patients with CDI before FMT, and one and eight weeks after FMT, were analysed. Analyses included microbiome composition analysis, alpha diversity, beta dispersion, and bile acid concentrations. Based on the weighted balance of four bile acids, a predictive model was created to predict variance in treatment efficiency using coda4microbiome . Results: CDI resolution in patients increased with higher abundances of Clostridia and Clostridiales in donor faeces, was positively associated with glycocholic acid, and negatively associated with 3-oxo-chenodeoxycholic acid in donor faeces. Using our predictive model, a linear regression was found where the predicted value explained 86% of the variance in efficiency score. When applying our model to the dataset with alternative filtering, it predicted a donor efficiency score (S _e ) with an average treatment efficiency of 73% for all donors, 83% for high-S _e donors and 67% for low-S _e donors. Conclusions: Donor-specific microbiome and metabolite compositions were linked to higher FMT success rates in the treatment of CDI, suggesting that predictive modelling can help select FMT donors. Our findings highlight a potential method for donor selection or optimization in FMT treatment of CDI.

Objective: To characterise gastrointestinal symptoms and bowel habits in healthy blood donors and explore symptom phenotypes and their associated factors. Methods: Between November 2020 and March 2023, 53 046 participants in the nationwide Danish Blood Donor Study completed a questionnaire including 13 gastrointestinal symptoms, defaecation pattern regularity, stool frequency, and stool consistency. We used a data-driven approach to explore symptom phenotypes and investigated associated factors by multinomial logistic regression. Results: Among the 53 046 participants (52% women), 68% (95% CI 67.5% to 68.3%) reported at least one of 13 gastrointestinal symptoms. The most frequent symptoms were bloating (40%), abdominal rumbling (40%), abdominal pain (17%), acid regurgitation (13%), heartburn (12%), diarrhoea (12%), nausea (12%), and constipation (10%). Half of the participants (50%) had a regular defaecation pattern (defined as generally the same stool consistency and stool frequency) consisting of Bristol Stool Form Scale 4 stools 1–3 times per day. Symptom phenotypes and their prevalence among 51 820 near-complete case participants were as follows: (1) no gastrointestinal symptoms (32%); (2) bloating and/or rumbling only (21%); (3) acid regurgitation and/or heartburn only (4%); (4) any other one or two symptoms (14%); (5) any three or four symptoms (18%); (6) any five or six symptoms (7%); (7) at least seven symptoms (3%). The acid regurgitation and/or heartburn only phenotype associated with obesity, and the remaining symptomatic phenotypes were associated with female sex, decreasing age, and an irregular defaecation pattern, even after excluding individuals with self-reported irritable bowel syndrome, lactose intolerance, or gluten intolerance. Conclusion: Most healthy adults, especially women younger than 50 years, experience gastrointestinal symptoms. Symptom phenotypes strongly correlate with sex, age, and bowel habits.