Can fecal transplantation treat the physical consequences of chronic stress? Employing fecal transplantation in a mouse model for chronic psychosocial stress

Abstract

Chronic psychosocial stress is known to affect the behavioural, physiological and inflammatory status of the organism and represents an accepted risk factor for the development and aggravation of affective and somatic diseases. Besides, chronic psychosocial stress is able to change the intestinal microbiota composition. Given that stress-related affective or gastrointestinal diseases are often accompanied by an altered intestinal microbiota composition and that the intestinal microbiome is able to influence the behaviour and physiology of an organism, it is very likely that chronic psychosocial stress mediates the vulnerability to develop chronic stress-induced diseases by changing the intestinal microbiota composition. If this hypothesis is true, a promising therapeutical approach to treat or to prevent chronic stress-induced changes in the intestinal microbiota composition and the associated consequences for the organism might be the transplantation of a healthy intestinal microbiota composition. An ideal model to address this hypothesis is the so called “chronic subordinate colony housing” (CSC) paradigm, as it induces chronic psychosocial stress in male mice and has repeatedly shown to alter the anxiety-related behaviour, physiological and inflammatory parameters and the intestinal microbiota composition. Therefore, to address the above mentioned hypothesis, it was the main aim of my thesis to examine i) if transplantations of feces from non-stressed single-housed control (SHC) mice into chronically stressed CSC mice can prevent CSC-induced alterations and ii) if transplantations of a “stressed” microbiome from CSC-donor mice can transfer CSC-induced effects into SHC mice. Besides, the study aimed to generally test if fecal transplantation (FT) via the rectal route instead of the commonly used oral route and without an antibiotic pre-treatment can affect stress-induced parameters in recipient mice. To do so, SHC- and CSC-recipient mice received repeated rectal infusions of SHC-donor feces on days 4 and 11 of the CSC paradigm. Anxiety-related behaviour was tested on day 19 and physiological and local colonic inflammatory parameters were assessed after sacrificing the mice in the morning of day 20. The same procedure was done with another set of SHC- and CSC-recipient mice that received CSC-donor feces. To see if rectal infusions per se have any effects on the assessed parameters, a set of SHC and CSC control mice received saline infusions at the respective days. The results of my thesis reveal that transplantations of SHC-donor feces had slightly stress-protective effects, indicated by the reduction of CSC-induced anxiety-related behaviour and by the prevention of CSC-induced thymus atrophy. However, transplantations of SHC-donor feces had no effects on CSC-induced adrenal enlargement. Moreover, the results of my study show that transplantations of CSC-donor feces did not transfer CSC-induced anxiety-related behaviour and physiological alterations to SHC-recipients. Moreover, the results of my study indicate that FT via the rectal route and without an antibiotic pre-treatment can affect certain chronic stress-induced parameters of the recipients as shown in the above-mentioned effects of SHC-donor feces on the behaviour and physiology of recipient CSC mice. Besides, my results show that local colonic inflammatory parameters were neither increased in saline nor in SHC- and CSC-recipient mice, indicating that the procedure of rectal infusions does not cause colonic inflammation in the recipients. Therefore, the rectal route can be regarded as an appropriate type of application for FT. In conclusion, the results of my study in combination with the recently published paper about this study (with me as second author) show that rectal transplantations of an “unstressed” microbiome can treat and/or prevent certain consequences of chronic psychosocial stress in the recipients. Therefore, in the future, transplantations of a “healthy” microbiome might be used as a therapeutical application for humans to treat and/or prevent negative consequences of chronic stress and to reduce the vulnerability to develop chronic stress-related diseases. Besides, the results of the published paper about this experiment reveal that some chronic stress-induced effects can be transferred to the recipient via FT, indicating that FT can also have undesirable side effects. Therefore, therapeutic approaches that use FT need to intensely screen fecal donors for present or previous chronic stress exposure.