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Fecal microbiota transfer may serve as a therapeutic tool for treating obesity and related disorders but currently, there is no consensus regarding the optimal donor characteristics. We studied how microbiota from vegan donors, who exhibit a low incidence of non-communicable diseases, impact on metabolic effects of an obesogenic diet and the potential role of dietary inulin in mediating these effects. Ex-germ-free animals were colonized with human vegan microbiota and fed a standard or Western-type diet (WD) with or without inulin supplementation. Despite the colonization with vegan microbiota, WD induced excessive weight gain, impaired glucose metabolism, insulin resistance, and liver steatosis. However, supplementation with inulin reversed steatosis and improved glucose homeostasis. In contrast, inulin did not affect WD-induced metabolic changes in non-humanized conventional mice. In vegan microbiota-colonized mice, inulin supplementation resulted in a significant change in gut microbiota composition and its metabolic performance, inducing the shift from proteolytic towards saccharolytic fermentation (decrease of sulfur-containing compounds, increase of SCFA). We found that (i) vegan microbiota alone does not protect against adverse effects of WD; and (ii) supplementation with inulin reversed steatosis and normalized glucose metabolism. This phenomenon is associated with the shift in microbiota composition and accentuation of saccharolytic fermentation at the expense of proteolytic fermentation.

Patients in the intensive care unit often lose a considerable fraction of their gut microbiome due to exposure to broad-spectrum antibiotics and other reasons. Dysbiosis often results in prolonged diarrhea and increase occurrence of multi-drug resistant pathogens in the colon with clinical consequences not yet well understood. Restoring the microbiome by fecal microbial transplantation (FMT) is a plausible therapeutic possibility, so far only documented in case reports and case series using very heterogeneous methodologies. Before FMT with critically ill patients can be tested in randomized controlled trials, there is a burning need to describe a standardized operating procedure (SOP) of the whole process, respecting the specifics of the critically ill population, such as the risk of the disrupted intestinal barrier and time-critical nature of the procedure. We describe the SOP that has been developed for experimental use in critically ill patients by a multidisciplinary team of intensivists, gastroenterologists, and microbiologists based on feedback from regulatory authority (State Institute for Drug Control of the Czech Republic). The hallmarks of these SOPs are multi-donor freshly frozen transplants guaranteed for 2 months consisting of seven aliquots from seven unrelated healthy donors and administered by a rectal tube. In this paper we discuss the rationale for this SOP and the process of its development in detail and release the full proposed SOP is in the form of an online appendix.