Table 2 Preclinical studies

Zhang et al. 2019 [28]

Chronic Stress Mice

Randomized Controlled Trial

FMT from wildtype (WT) and NLRP3 KO mice to chronic unpredictable stress (CUS) mice

WT and NLRP3 KO mice

SPT, FST, TST, and OFT

• Transplantation of the NLRP3 KO gut microbiota ameliorated CUS-induced depressive-like behaviors.

Li et al. 2019 [21]

Antibiotic treated 8 male WT and 8 male chronic unpredictable mild stress (CUMS) mice

Randomized Controlled Trial

Oral FMT for 2 weeks from WT and CUMS mice to antibiotic-treated WT and CUMS mice

8 WT mice and 8 CUMS mice

SPT, OFT, EPM, FST

• FMT of CUMS microbiota induced anxiety-like and depression-like behavior in the recipient mice

Lv et al. 2019 [22]

Antibiotic treated Male rats with and without CUS

Randomized Controlled Trial

3-day oral FMT from WT and CUMS mice to antibiotic-treated rats with and without CUS

WT and CUMS mice

SPT, OFT, EPM, FST

• Transplantation of CUMS Microbiome Induces Depression-Like Behaviors in Antibiotic-Treated Rats as shown via a decrease in time spent in the central area in the OFT and increased immobility in the TST

Xiao et al. 2018 [29]

6–8 week male C57BL/6 mice

Randomized Controlled Trial

14 days of saline or oral FMT from alcohol or water exposed mice to healthy control mice

Alcohol-exposed and water-exposed mice

FST and TST

• FMT from alcohol-exposed mice induced depressive behavior in the recipients, shown by significant results in FST and TST

• Alcohol withdrawal induced symptoms were transmitted to healthy controls

Yang et al. 2019 [68]

Antibiotic treated two-month-old male C57BL/6 mice

Randomized Controlled Trial

14 days of FMT from rats to antibiotic treated C57BL/6 mice

Two-month old

Mechanical withdrawal test (MWT), Tail flick test (TFT), SPT, locomotion, TST, and FST

• Antibiotic administration significantly aggravated the MWT scores, latency of TFT, and depression-like behaviors.

Sprague Dawley rats with and without anhedonia

• FMT from rats with anhedonia significantly aggravated behavioral abnormalities, pain, depression-like, and anhedonia-like behaviors in recipient mice

• Antibiotics-treated pseudogerm-free mice showed depression-like and anhedonia-like phenotype compared to control group, which were improved by FMT from mice without anhedonia.

Tillmann et al. 2019 [32]

24 adult male Flinders sensitive line (FSL) and 24 Flinders resistant line

Randomized Controlled Trial

FMT from FRL, saline, or FSL rats to FRL and FSL rats administered every third day over a 16-day period

FSL, FRL, or saline rats

OFT and FST

• Rats receiving FRL feces struggled less than saline-treated ones while there was no difference between FSL feces and saline or FSL and FRL feces.

• Rats receiving FSL feces had significantly increased immobility compared with saline, whereas FRL feces did not differ from saline.

• No difference in immobility between FSL and FRL feces.

Langgartner et al. 2018 [25]

Male C57BL/6 N chronically stressed mice via chronic subordinate colony (CSC)

Randomized Controlled Trial

Repeated FMT from non-stressed single-housed control (SHC) mice

Non-stressed, SHC Male C57BL/6 N mice

OFT and open-field/novel object (OF/NO) test

• SHC feces transplantation had mild stress-protective effects as shown by an improvement of CSC-induced thymus atrophy, anxiety, systemic low-grade inflammation, and alterations in bone homeostasis.

• CSC feces transplantation slightly aggravated CSC-induced systemic low-grade inflammation and alterations in bone homeostasis in SHC and/or CSC animals.

Jiang et al. 2020 [30]

18, 7-weeek old, antibiotic treated C57BL/6 J mice

Randomized Controlled Trial

FMT from 6 control, 6 alcohol-induced depression, and 6 alcohol-induced depression nicotinamide riboside (NR) treated mice after 3 weeks of antibiotic treatment

Control, alcohol-induced depression model, and alcohol-induced depression model NR-treated C57BL/6 J mice

SPT, FST, EPM, and Y-Maze

• Mice receiving FMT from alcohol induced depression model exhibited depression-like behaviour

• Mice receiving FMT from control or NR mice did not exhibit depression-like behaviour.

Schmidt et al. 2020 [33]

Adult female Lewis rats

Randomized Double-Blind Sham Controlled Trial

FMT from healthy rats is given to rats with spinal cord injury (SCI)

Healthy, uninjured, adult female Lewis rats

Light-dark box, Cylinder test, SPT, EPM, OFT

• FMT from healthy rats significantly reduced depression and anxiety-like behaviour resulting from SCI in the elevated plus maze and light-dark box (significantly more time in open arms of the maze and light box)

Siopi et al. 2020 [23]

8-week old, antibiotic-treated, GF C57BL/6 J mice

Randomized Controlled Trial

Antibiotic-treated GF mice receive FMT from 10 control, or 10 unpredictable chronic mild stress (USMS) mice

Control or UCMS mice

TST, FST, OFT, EPM, Light-dark Box

• FMT from UCMS mice resulted in despair-like behaviour in the TST and FST (increased immobility time in both)

Pearson-Leary et al. 2019 [24]

Experimental Intruders: Singly housed male Sprague–Dawley rats

FMT from vulnerable, resilient, and control rats delivered via oral gavage to naïve recipient rats once daily for 5 days.

SL/vulnerable, LL/resilient rats, or control rats

FST and SIT

• FMT from SL/vulnerable rats to naïve, non-stresses rats promotes some stress vulnerability

• No differences in time spent interacting in SIT between recipient groups suggesting no difference in anxiety-like behavior

Residents: Male Long–Evans (LE) retired breeders (600–800 g) were used as residents.

• Rats treated with vulnerable microbiota had increased passive depression-like behaviours (decreased latency to immobility, less time swimming, and increased time spent immobile)

• SL/vulnerable microbiota treated rats also spent less time climbing, but this was not significant