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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