TABLE 2.

Microbial intervention in schizophrenia

Source	Study design	Sample size (n)	Study population	Microbial strains	Treatment duration	Key finding(s)
Fecal microbiota transplantation
Xie et al., 2019  (442)	Case report, pre and postintervention assessment	1 participant	1 male MDD patient with GI symptoms and alopecia, 86 yrs old	Six-time FMT via colonoscopy, 22-yr-old healthy male donor	18 mo	Improvement in symptoms of depression.
						Increased BMI, improvement of appetite, no abdominal pain or distension.
Cai et al. 2019 (443)	Case report, pre- and postintervention assessment	1 participant	1 female MDD patient, 79 yrs old	6-yr-old grandson, single-time FMT via gastroscope	6 mo	Optimization of the intestinal microflora of patients with depression through the use of FMT.
						Substantial increase and reduction in Firmicutes and Bacteroides count, respectively.
						Alleviate depression-related symptoms by restoring or reconstructing the constitution of the intestinal microflora.
Liu et al. 2020 (473)	Preclinical, animal study	18 participants	18 8-wk-old GF rats	Microbiota transplantation from healthy or depressed humans between ages 18 to 60 into GF mice	4 wks	Depression microbiota-treated rats demonstrated depression-like behavior.
						The decrease of hippocampal neurotransmitter levels through depression microbiota transplantation.
						Depression microbiota transplantation induced abnormalities in the HPA axis, an inflammatory reaction, and mitochondrial dysfunction.
Probiotics
Severance et al.,  2017 (235)	Randomized, placebo-controlled, longitudinal pilot study	56. participants	Aged between 18–65 yrs, patients with at least moderately severe psychotic symptoms	Combined B. animalis subsp. lactis strain Bb12 and L. rhamnosus strain GG	14 wks	In SCZ, probiotic supplementation contributes to the reduction of elevated Candida yeast antibody levels.
						Relieved yeast-related bowel discomfort over compared to placebo.
						Candida albicans seropositivity was associated with worse psychiatric symptoms.
Okubo et al., 2019  (444)	open-label single-arm study	29. participants	Patients aged 20 yrs or more; not admitted to hospital within at least 6 mo after last discharge	Bifidobacterium breve A-1	8 wks	Probable enervation of depressive and anxiety symptoms in SCZ by enhancement in the function of gastrointestinal epithelial barrier.
Dickerson, 2014  (234)	A randomized, placebo-controlled, double-blind trial	58 participants	Aged between 18 to 65 yrs, patients with at least moderately severe psychotic symptoms.	Combined B. animalis subsp. lactis strain Bb12 and L. rhamnosus strain GG	14 wks	Probiotic administration might reduce the development of severe bowel difficulties in SCZ patients.
Tomasik et al. 2015  (445)	A randomized, Placebo-Controlled Trial	57. participants	65. outpatients diagnosed with schizophrenia or schizoaffective disorder	B. animalis subsp. lactis strain Bb12, Lactobacillus rhamnosus strain GG	14 wks	Probiotic administration may ameliorate gastrointestinal leakage control in SCZ.
Synbiotics
Haghighat et al.,  2019 (446)	Three-arm parallel design, placebo-controlled, double-blind, randomized controlled trial	75 participants	Clinically stable hemodialytic patients with MDD, aged 30 to 65 yrs	Synbiotic (15 g of prebiotics, 5 g of probiotic containing Lactobacillus acidophilus T16, Bifidobacterium bifidum BIA-6, B. lactis BIA-7, and B. longum BIA-8) probiotics (5 g probiotics as in synbiotic group with 15 g of maltodextrin as placebo) or placebo (20 g of maltodextrin)	12 wks	Improvement in serum BDNF level and depression symptoms through synbiotic supplementation in comparison to the probiotic administration in subjects with HD, particularly in depression symptoms.