TABLE 3.

Interventions altering the gut microbiome in alcohol-related depression and anxiety.

Recipients	Manipulation	Change in microbiome	Change in behaviors	Change in other system	Citations
Alcohol-dependent patients n = 60 (high IP n = 26 and low IP n = 34) Control group n = 15	3 weeks of detoxification and rehabilitation program	Only high IP group showed dysbiosis ↓Overall bacterial load: ↓Ruminococcaceae family ↑Lachnospiraceae family ↑Blautia Not in low IP patients	High IP group: remained anxiety, depression, and alcohol craving even after 3 weeks abstinence Low IP group recovered	NA	Leclercq et al., 2014b
3-week-old mice pretreated by antibiotics and polyethylene glycol were performed FMT and behavioral testings (FMT-Alc, FMT-Con n = 12/group)	FMT from alcohol-dependent patients every other day in a total of 7 days and 3 times	↓F. prausnitzii ↑A. muciniphila ↓α-diversity ↓Total bacterial load ↑Relative abundance of Verrucomicrobia	↓Social behavior ↑Depressive-like behavior ↑Stress level No difference in anxiety-like behavior and locomotor activity	Attenuated immune system (altered immune responses of Th2 and Th17 cells) Loss of intestinal homeostasis (↓Reg3g and Lcn2) Disturbances of brain function including myelination, neurotransmission, and inflammation	Leclercq et al., 2020
Healthy mice (Water group n = 12; Alcohol group n = 12; Saline group n = NA; FMT group n = 5)	FMT from alcohol-exposed mice for 14 days	↓Bacteroides ↑Erysipelotrichia ↓Lactobacillaceae ↓Bacilli ↓Parabacteroides ↓Alloprevotella ↑Blautia	Developed depression-like behaviors	Alcoholism-relating genes: ↓BDNF and CRHR1 ↑Oprm1	Xiao et al., 2018
Mice with chronic alcohol exposure (Control group, Alcohol group, FMT group n = 6-7 per group)	FMT from 3 young male physically and mentally healthy volunteers for 2, 4, or 5 weeks	NA	5 weeks rather than 2 weeks FMT alleviated alcohol-induced anxiety and depression	NA	Xu et al., 2018
Alcohol-treated group n = 18 Control group n = 10	Increased concentration of alcohol in their drinking water from 2, 4, to 6% every 3 days, and finally reached 8% in a total of 21 days	↑Actinobacteria and Cyanobacteria ↑Adlercreutzia spp., Allobaculum spp., and Turicibacter spp. ↓Helicobacter spp.	Alcohol-induced anxiety/depression-like behaviors	Decreased GABA1 and BDNF levels correlated with behaviors change	Xu et al., 2019
Mice pretreated by antibiotics (FMT-Alc n = 13-14, FMT-Con n = 11-12)	FMT from patients with alcoholism every other day in a total of 13 days and 7 times	↓Bacteroidetes ↑Firmicutes	↑Alcohol preference ↑Anxiety/depression-like behaviors ↓Social interaction behaviors	↓BDNF, α1GABAAR in mPFC ↓mGluR1, PKCε in Nac	Zhao et al., 2020
Mice ethanol consumption behavior were tested in a binge-like “Drinking in the Dark” model for 6 weeks (Water groups-H2O, H2O-20E, ABX groups-ABX, ABX-20E. n = 8/group)	2 weeks pretreatment of ABX in drinking water	↑Bacteroidetes ↓Firmicutes ↑Verrucomicrobia	↓Anxiety-like behavior during ethanol withdrawal period ↑Ethanol consumption Firmicutes negatively while Bacteroidetes and Verrucomicrobia positively correlated to ethanol intake levels	NA	Reyes et al., 2020