Variable Colonization after Reciprocal Fecal Microbiota Transfer between Mice with Low and High Richness Microbiota

Abstract

Several associations have been made between characteristics of the resident gut microbiota and human health and disease susceptibility. Animal models provide the means to test these correlations prospectively and evaluate causality. Experimental fecal microbiota transfer (FMT), or the intentional transplantation of gut microbes into recipient mice depleted of their autochthonous microbes with antibiotics, is a commonly used method of testing these relationships. The true completeness of microbial transfer through such procedures is poorly documented in the literature, particularly in the context of reciprocal transfer of microbes between recipient and donor mice harboring microbial populations of differing richness and diversity. Moreover, it is unclear whether the use of frozen fecal contents or cecal contents would confer any difference in the outcomes of transfer. Herein, groups of mice colonized with distinct gut microbiota of differing richness and composition were used in a reciprocal FMT study, with different groups receiving transfer of material prepared from fresh cecal contents, fresh feces, or frozen feces. Targeted 16S rRNA gene amplicon sequencing was used at intervals throughout the study to characterize the microbiota. Notably, despite comparable depletion of the microbiota in recipient mice prior to transfer, donor-specific taxa reliably colonized recipients only when relatively rich donor material was transferred to mice originally colonized with a simpler microbiota. It is unclear whether these differences were due to differences in the endogenous recipient microbiota or host factors induced in early life by microbial factors. These findings are of practical import for researchers using FMT to prospectively assess the influence of the gut microbiota in mouse models, and to those studying host-microbial interactions and their influence on gut barrier function.

Restoration of short chain fatty acid and bile acid metabolism following fecal microbiota transplantation in patients with recurrent Clostridium difficile infection

“…Following FMT in obese individuals, Li et al identified that the dominance and resilience of transplanted species such as Roseburia hominis , Ruminococcus lactaris , and Akkermansia muciniphila were not consistently observed across individuals (53). In mice, variable colonization that can lead to functionally diverse microbiota communities has been observed in germ-free mice colonized by human microbiota (54, 55) and antibiotic-treated mice colonized by different mouse communities (56). Together, the baseline microbial community of FMT recipients and the stochastic nature of the microbial input that colonizes the recipient likely impact the ability of a microbial community to produce certain functions.…”

Faecal freezing preservation period influences colonization ability for faecal microbiota transplantation

“…; Ericsson et al . ). Water bottles were monitored to confirm consumption and mice were monitored on a daily basis for signs of dehydration.…”

“…Prior to fresh and frozen FMT, the recipient mice were provided ampicillin (1 g l À1 ; Wako Pure Chemical Co. Ltd., Osaka, Japan), neomycin (1 g l À1 ; Wako Chemical Co. Ltd), metronidazole (1 g l À1 ; Wako Chemical Co. Ltd) and vancomycin (500 mg l À1 ; Wako Chemical Co. Ltd) in the drinking water for five consecutive days following the previous study (Rakoff-Nahoum et al 2004;Ericsson et al 2017). Water bottles were monitored to confirm consumption and mice were monitored on a daily basis for signs of dehydration.…”

Stable Engraftment of a Human Gut Bacterial Microbiome in Double Humanized BLT-mice

“…In a study by Zhou et al, NSG and C57BL6/J mice whose native microbiota were depleted by antibiotics followed by FMT had no significant differences in diversity but did observe significant differences in which species colonized[39]. A study done by Ericsson et al showed that it is easier to transfer high diversity fecal donor samples into low diversity recipients, which could help to explain the success of engraftment and stability in our model[30]. Many questions remain as to the best antibiotic preconditioning regimen, the timing of fecal transplants, the total number of fecal transplants, the route of administration (oral versus rectal), the use of antacids, and preconditioning with osmotic laxatives such as polyethylene glycol, diet, and housing.…”

“…Many different methods and antibiotic regimens have been used for preconditioning of mice prior to fecal transplantation[28–30]. Different combinations and durations of antibiotic treatments may increase the efficiency of the fecal transplant into the host[29].…”