Skip to main content

Table 3 Preclinical studies with human donors

From: Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review

Study

Sample characteristics

Study design

Intervention

Donor

Measurement

Key findings and conclusions

De Palma et al. 2019 [43]

141 GF NIH Swiss Mice

Randomized Controlled Trial

FMT from IBS patients and healthy donors to GF mice

4 Anxious IBS-D patients, 4 non-anxious IBS-D patients, Mean age: 40 years old; 5 healthy human controls (HHC), Mean age: 42 years

Donors: HAM-A

• FMT from anxious IBS-patients to mice produced anxiety behaviors in mice

Recipients: Light-dark preference test and step-down test

• FMT from IBS patients with normal anxiety and from healthy controls to GF mice showed no significant anxious behaviors in GF mice

• Akkermansia was associated with anxiety behaviors in mice

Hata et al. 2019 [42]

Germ-free (GF) BALB/c mice

Randomized Controlled Trial

Oral FMT with and without pre-treatment with live Bacteroides vulgatus to GF mice

4 AN patients, Mean age: 23 years, BMI 13.7; 4 HHC, Mean age: 25.3 years, BMI 21.6

Donors: DSM diagnosis of AN

• FMT from AN patients induces anxiety-like and compulsive behaviors in GF recipient mice and impairs body weight gain

Recipients: Open Field and Marble Burying

• Pre-treatment with B. vulgatus attenuates compulsive behavior

Zhao et al. 2019 [39]

Male C57BL/6 J mice with antibiotic gut microbiota suppression, 6 weeks old

Randomized Controlled Trial

FMT via intragastric administration every other day for 13 days to antibiotic treated mice

Patients with and without alcoholism, Ages 35–40

Donors: ICD-10 diagnosis of alcoholism

• FMT from patients with alcoholism induced spontaneous alcohol dependence in mice

Recipients: Open field test (OFT), alcohol preference test (APT), elevated plus maze test (EMT), tail suspension test (TST), and social interaction test (SIT),

• FMT-Alc group exhibited anxiety-like and depression-like behaviors changes and significantly declined social interaction behaviors

Huang et al. 2019 [36]

GF Mice

Randomized Controlled Trial

FMT from MDD patients and healthy controls to GF mice

5 MDD patients; 5 HHC

Donor: DSM-IV diagnosis of depression and HAM-D

• FMT from MDD patients resulted in significantly increased immobility times for the FST and TST

Recipient: OFT, TST, forced swimming test (FST), buried food pellet test (BFP) and olfaction behavior test (via modified BFP)

• The center motion distance (OFT) also significantly decreased compared to controls

• The latency for finding the object by depressed mice was significantly longer than that by healthy controls indicating impaired olfaction.

Kelly et al. 2016 [34]

Adult, male Sprague Dawley rats treated with antibiotic cocktail for 28 days

Randomized Controlled Trial

3-day pooled sample oral FMT from MDD patients and healthy controls to antibiotic treated rats, with booster inoculations given twice per week throughout the study.

Pooled fecal samples from 3 severely depressed MDD patients; pooled fecal samples from 3 HHC

Donor: Perceived stress scale (PSS), Beck Depression and Beck Anxiety Scales, HAM-D, etc.

• Rats receiving FMT from MDD patients demonstrated anhedonia-like behaviours as shown by a significant decrease in sucrose intake without affecting fluid intake in SPT

Recipients: Sucrose preference test (SPT), OFT, EMT, FST

• Rats receiving FMT from MDD patients also exhibited anxiety-like behaviours as shown by a significant decrease in visits to the open arms in the EMT and a reduction in time spent in the centre in the OFT.

• In the forced swim test, there were no significant differences between the groups in immobility time, swimming, or climbing.

Xu et al. 2018 [40]

110 male C57BL/6 mice aged 4 to 5 weeks exposed to chronic ethanol

Randomized Controlled Trial

FMT 1: FMT at the end of chronic alcohol exposure period

3 HHC

Recipients: OFT, TST, FST, and APT

• FMT 1 could not alleviate alcohol-induced anxiety or depression.

FMT 2: FMT at middle (6%) of alcohol exposure period.

• FMT 2 alleviated alcohol-induced depression in TST

FMT 3: FMT at the beginning of whole exposure period

• FMT 3 modulated anxiety and significantly improved depression.

• FMT 3 decreased Anxiety in OFT and significantly improved depression in TST.

• No significant alcohol preference alternation in FMT-treated mice.

Zheng et al. 2016 [35]

Male GF Kunming mice and specific pathogen free (SPF) Kunming mice, 6–8 weeks old

Randomized Controlled Trial

Pooled sample FMT from MDD patients and HHC to GF mice

5 Male MDD patients, ages 26–61; 5 Male HHC, ages 29–6

Recipients: OFT, FST, TST

• Absence of gut microbiota in germ-free (GF) mice resulted in decreased immobility time in the FST compared to conventionally raised HC mice

• The gut microbiota compositions of MDD patients and HC were significantly different with MDD patients characterized by significant changes in the relative abundance of Firmicutes, Actinobacteria and Bacteroidetes.

• FMT from MDD patients to GF mice resulted in depression-like behaviors compared to HC colonization

• Weight was not significantly different between groups

Chen et al. 2020 [69]

ASD Model Mice

Randomized Controlled Trial

Pooled samples from Healthy Human donor gut bactiera (M + O) or cultured bacteria from original pooled healthy donor gut bacteria (M+ F)

Original healthy Human bacteria (M + O); in vitro cultured bacteria from healthy human donor (M + F)

OFT, Marble Burying Test, Self-grooming, Three-Chamber Social Test

• M + O spent significantly more time and had more entries in the OFT, significantly lower % of marbles burried, and significantly lower % of gromming time.

• M + F had significantly lower % of marbles burried, and % of grooming time.

• These results suggest that FMT from organic in vivo microbiota may be better at alleviating depressive and anxiety-like behaviours, but that both in vivo snd in vitro bacteria transplantation have beneficial properties.

Liu et al. 2020 [37]

18, 8-week old GF rats

 

Microbiota from healthy or depressed humans were transplanted into GF mice

Depressed or Healthy Humans between ages 18–60

Donors: 24+ points on HAM-D, DSM-5 diagnosis of MDDRecipients: FST, SPT

• Rats receiving depression microbiota exhibited depression-like behavior (immobility time in the forced swimming test was significantly higher than in control groups)

• From the first week to the fourth week, the saccharine preference index was significantly lower in the depression micro- biota group than that in the blank control and healthy microbiota groups