Gut microbiome transfer—Finding the perfect fit

Abstract

Gut microbiome transfer (GMT; also referred to as faecal microbiota transplantation or FMT) has been propelled from fringe therapy to mainstream science as a highly effective treatment for recurrent Clostridioides difficile infection. As a result, there has been great interest in the potential efficacy and safety of GMT in treating other medical conditions, for example inflammatory bowel disease, and more recently as a novel therapy for obesity and metabolic diseases. For these chronic conditions, the results from clinical trials have been mixed. Further, specifically in obesity and metabolic diseases, there are limited available data, with only a few published studies with a small number of participants and short duration of follow‐up. Therefore, this review aims to explore the human, microbial and formulation factors that may affect the success of GMT. This includes various aspects in the preparation and administration of GMT, such as stool processing, modes of delivery, pretreatment with antibiotics and/or bowel lavage, frequency of GMT and possible use of precision bacteriotherapy. In addition, we examine the potential use of GMT in obesity, type 2 diabetes and metabolic diseases based on current available literature, highlighting some recent advances in GMT research in this area, as well as potential adverse effects after GMT therapy.

Effects of Fecal Microbiome Transfer in Adolescents With Obesity

“…[12][13][14][15][16] However, those trials examined body weight as a secondary outcome, and were not powered to detect effects on body weight. 9,[12][13][14][15][16] Our finding of a small reduction in A/G ratio, and therefore a likely reduction in visceral adiposity is a new observation that has not been reported in previous studies. [12][13][14][15][16] This finding of improved A/G ratio with FMT corresponded to an approximately 2% to 3% reduction in the proportion of abdominal fat, and was particularly marked among female participants.…”

“…7,8 Animal studies successfully altered body phenotypes by fecal microbiome transfer (FMT); germ-free mice that received microbiota from human donors with obesity developed obesity, whereas mice that received microbiota from human donors postbariatric surgery remained lean. 7,[9][10][11] This evidence highlights that FMT could be a treatment modality for human obesity. 4,10,11 Evidence on the therapeutic benefits of FMT in obesity and metabolic syndrome is limited.…”

“…In contrast to other studies whereby participants received FMT from different donors, we were able to standardize treatment by using repeated donations from the same donors throughout the trial and thus reducing potential confounders because of donor-specific effects. 9,12,13,16 Limitations This study had several limitations. First, a limitation of our study was that diet and physical activity were not tightly regulated.…”

“…4,10,11 Evidence on the therapeutic benefits of FMT in obesity and metabolic syndrome is limited. 9 Five studies examined the effect of FMT on insulin sensitivity and its safety among adults with obesity and metabolic syndrome. [12][13][14][15][16] A temporary improvement in insulin sensitivity was demonstrated in 2 of these studies.…”

Power calculations for detecting differences in efficacy of fecal microbiota donors

“…In this model, donor effects are detected by searching for an association between some continuous-valued donor biomarker and the associated patients’ outcomes. This approach was designed to model the statistical tests used to search for donor effects in previous FMT studies, where the biomarker in question is typically the donor’s gut microbiota community diversity or the abundance of particular microbial taxa in the donor [21].…”