Table 1.

Human Probiotic Trial Designs and Outcomes.

Probiotic Treatment	Blinding Status and Study Design	Sex and Age, years	Anxiety/ Depression / Emotional Behavior	Cognition/ Social Function	Other Probiotic Associated Outcomes	Reference
Infant/Child
L. rhamnosus GG ATCC531031 × 10¹⁰ CFU (n = 46) or placebo (n = 47) Q.D. breastfeeding mothers 14 to 28 days pre-gestation and infants 180 days post-gestation	Double-blind Infants having a mother, father, or sibling with atopic dermatitis, allergic rhinitis, or asthma	Sex not reported Age pre-gestation w/followup at 3, 6, 12, 18 and 24 months	^*NSE on fussing/crying	^§NA	^#PROT ↓ fecal Clostridia at 6 and 24 months ^NSE fecal Bifidobacterium, Bacteroides, Lactobacillus, or Enterococcus*	(Rinne et al., 2006)
L. renteri DSM 17938 1 × 10⁸ CFU (n = 238) or placebo (n = 230) drops P.O. Q.D. for 90 days	Double-blind 38-40-week gestation, Apgar >8 at 10 min, normal birth weight Exclusions: antibiotic, antacid, or PPI use	Male (n = 242) Female (n = 226) Age 0.019 (< 7 days)	^#PROT ↓ fussing or crying	^§NA	^#PROT ↓ constipation, regurgitation, and healthcare costs	(Indrio et al., 2014)
L. reuteri DSM 17938 1 × 10⁶ CFU/g (n = 60) or placebo whey formula (n = 62) Q.D. for 98 days	Double-blind Gestation ≥37 weeks, singleton-birth weight 2500 - 4500g, formula-fed 3 days prior to enrollment. Exclusions: Cow milk allergy, medical disease, hospitalized, IV antibiotic or oral medication (except thrush), ^#PROT 7 days before enrollment	Male (n = 78) Female (n = 86) Age 0.038 (14 days)	^#PROT ↑ irritability 14 days post - treatment (^*NSE overall)	^§NA	^*NSE weight gain, sleep, body length, head size, stool	(Cekola et al., 2015)
L. renteri DSM 17938 1 × 10⁸ CFU (n = 85) or placebo (n = 82) 5 drops P.O. Q.D. for 30 days	Double-blind Wessel’s colic Exclusions: <2500 g birth weight, medical disease, cow milk allergy, antibiotic or L. reuteri use by infant or mother before enrollment	Male (n = 85) Female (n = 82) males > Age < 0.249 (91 days)	^*NSE on fussing/cry ing in breastfed infants ^#PROT ↑ fussing crying in formula fed infants	^§NA	^*NSE maternal mental health	(Sung et al., 2014)
L. reuteri ATCC55730 (n = 20), B. lactis BB-12 (n = 20) 1 × 10⁷ CFU/g, or placebo (n = 19) in formula Q.D. for 28 days	Double-blind All infants were formula-fed by parental choice prior to enrollment Exclusions: <36 weeks of gestation, chronic disease, congenital abnormalities, <2500 g birth weight, allergies, atopic disease, probiotic exposure within 4 weeks of enrollment	Female (n = 19) Male (n = 40) Mean Age 0.093 (3-65 days)	^*NSE on fussing/crying	^§NA	^*NSE crying, night awakening, daily gas, stool effort and consistency	(Weizman and Alsheikh, 2006)
L. reuteri Biogaia AB (n = 124) 1 × 10⁸ CFU or placebo (n = 125)5 drops Q.D. from birth until discharge	Double-blind Preterm infants with a gestational age of ≤ 32 weeks, birth weight ≤1500 g, Follow-up analyses of (Oncel et al., 2014)	Male (n = 133) Female (n = 116) Age birth and follow up 18 to 24 months	^§NA	^*NSE neurocognition (BSID-II-PDI and MDI)	^*NSE visual impairment, hearing impairment	(Akar et al., 2017)
S. thermophilus, B. animalis ssp. lactis BB-12, and L. bulgaricus General Mills 5 × 10⁹ CFU/100 mL + 1 g inulin (n =76) yogurt drink or non-synbiotic acidified placebo milk drink (n =73) Q.D. for 112 days	Double-blind Child care attendees Exclusions: premature or low birth weight, allergy, atopic, or medical disease, GI surgery, lactase deficiency or milk intolerance, antibiotic use within 4 or probiotic use within 2 weeks of study enrollment	Males (n = 74) Females (n = 75) Age 1-4 Mean Age 2.5	^§NA	^#PROT ↑ in social function (Ped-QOL)	^#PROT ↑ in school function (Ped-QOL), watery stool ^#PROT ↓ fever	(Ringel-Kulka et al., 2015)
Older Adult
L. reuteri DSM 17938 1 × 10⁸ CFU stick pack with rhamnose, galactooligosacch aride B.I.D. (n = 125) or placebo (n = 124) for 84 days	Double-blind Age 65+ Exclusions: GI or IBD, use of GMMS or PPI, participation in other clinical trials within 3 months of enrollment	Male (n = 97) Female (n = 152) Age 65+ Mean age 72.3	^*NSE stress, anxiety, or well-being (HADS, PSS, EQ-5D-5L)	^§NA	^*NSE GSRS	(Ostlund-Lagerstrom et al., 2016)
65 mL milk drink w/ L. casei Shirota 1 × 10⁸ CFU/mL Q.D. or placebo for 21 days	Double-blind Self-reported healthy older adults with stable hypertension for 3 months and diabetes mellitus under dietary or medication control	Male (n = 51) Female (n = 75) Age 48-79 Mean age 61.8	^#PROT ↓ depression only for sample subset with poor baseline mood (POMS)	^*NSE verbal fluency, episodic memory ^#PROT ↓ mental clarity	^#PROT ↑ confidence ^*NSE eating behavior	(Benton et al., 2007)
L. helveticus IDCC3801 four 125mg (n = 10), 250mg (n = 7), 500mg (n = 9) or placebo (n = 10) tablets Q.D. for 84 days	Double-blind Proficiency using computers, education above middle school, ≥ 24 MMSE- Korean, BMI≤ 16 and ≤ 35 Exclusions: Axis I disorder or Axis I treatment within 5 years of enrollment, ≥ 8 GDS-SF, alcohol abuse/dependence within 3 months, GI disease or GI surgery, significant neurological or medical illnesses, supplement or herbal medicine use during the 4 weeks prior to enrollment, compliance < 70% at each study visit	Male (n = 20) Female (n = 16) Age 60-75 Mean Age 65.0	^*NSE stress (PSS) and depression (GDS-SF)	^#PROT ↑ RVIP	^*NSE serum BDNF and whole blood viscosity	(Chung et al., 2014)
VSL#3 4.5 × 10¹¹ CFU B.I.D. (n = 10) or placebo (n = 8) for 28 days after surgery	Double-blind Laparoscopic colorectal surgery patients	Male (n = 9) Female (n = 9) Age 70+ Mean Age 72.2	^§NA	^#PROT ↑ social function (SF-36)	^#PROT ↓ bowel movement	(Pellino et al., 2013)
200 mL milk drink with L. acidophilus, L. casei, L. fermentum, B. bifidum Tak Gen Zist Pharmaceuticals 2 × 10⁹ CFU/g (n = 30) or placebo (n = 30) for 84 days	Double-blind NINDS-ADRDA diagnosis of Alzheimer’s Disease Exclusions: chronic/metabolic illnesses, probiotic consumption 6 weeks prior to enrollment	Female (n = 48) Male (n = 12) Age 60-95 Mean Age 79.8	^§NA	^#PROT ↑ cognition (MMSE)	^#PROT ↓ VLDL, QUICKI, MDA, HOMA-B, hs-CRP ^#PROT ↑ HOMA-IR	(Akbari et al., 2016)
Young/Middle-Aged Adult
Fermented milk L. casei Shirota 1 × 10⁹ CFU/mL Q.D. (n = 24) or placebo drink (n = 23) for 56 days	Double-blind Healthy Japanese Students Exclusions: smokers, age > 30, allergies, mental or medical disease, medication use	Male (n = 26) Female (n = 21) Age < 30 Mean Age 27.9	^#PROT ↓ anxiety (STAI) one day before exam	^§NA	^#PROT ↑ increase fecal serotonin post-exam ^#PROT ↓ incidence cold and abdominal illness	(Kato-Kataoka et al., 2016)
Fermented milk with L. casei Shirota 1 × 10⁹ CFU/mL Q.D. (n = 52) or placebo (n = 41) for 56 days **new subjects added to study above	Double-blind Healthy Japanese students Exclusions: smokers, age > 30 years, taking medications, mental illness, and score over 60 on SDS	Male (n = 76) Females (n = 64) Age < 30 Mean Age 22.9	^*NSE anxiety (STAI)	^§NA	^#PROT ↓ cold/flu symptoms and cortisol 1 day before exam See Table 2 for Rat Trial Outcomes	(Takada et al., 2016)
Fermented milk L. casei Shirota 1 × 10⁹ CFU/mL Q.D. (n = 48) or placebo drink (n = 46) for 56 days before exam and 14 days after **pooled sample with above studies	Double-blind 4^th grade medical students Exclusions: age > 30 years; physical or mental illness, taking medications; smoker, milk or food allergy	Male (n = 55) Female (n = 39) Age < 30 Mean Age 22.7	^#PROT ↑ stress (exam) induced sleep disturbance	^#PROT ↑ delta power > 20% immediately prior to exam	^§NA	(Takada et al., 2017)Takada et al., 2017)
L. casei Shirota 2.4 × 10⁹ CFU (n = 19) or placebo (n = 16) Q.D. for 60 days	Double-blind Stable Chronic Fatigue Syndrome Exclusions: bedridden, meeting criteria for neuropsychiatric disorders except depression or anxiety	Male (n = 8) Female (n = 27) Age 18-65 Mean Age 41.2	^#PROT ↓ depression (BDI)	^§NA	^§NA	(Rao et al., 2009)
L. casei Shirota 1 × 10¹⁰ CFU Q.I.D. (n = 36) or placebo (n = 36) for 21 days	Double-blind Smokers mean cigarettes/day = 20 Exclusions: other health problems	Male (n = 72) Age 40-60 Mean Age 50.3	^*NSE anxiety (STAI) or job stress	^§NA	^#PROT ↑ NK cell activity	(Reale et al., 2012)
L. rhamnosus CGMCC1.37241.6 × 10⁸ CFU/capsule B.I.D. (n = 62) or placebo (n = 63) for 168 days	Double-blind BMI 29 - 41 kg/m², weight change < 5 kg 3 months before screening Exclusions: pregnancy, breastfeeding, menopause or obesity comorbidities	Male (n = 45) Female (n = 60) Age 18-55 Mean Age 36.0	^#PROT ↓ depression (BDI) ^*NSE PSS, STAI, BES	^#PROT ↑ cognitive restraint	^#PROT ↓ body esteem, and ↓ weight, hunger, and disinhibition in female subjects only	(Sanchez et al., 2017)
L. helveticus Lafti 2 × 10¹⁰ CFU (n = 20) or placebo (n = 19) Q.D. for 98 days	Double-blind National or European/World championship athletes Exclusion: chronic diseases, surgery within 1 year of enrollment, probiotic sensitivity, probiotic or antibiotic use 1 month before enrollment	Male (n = 29) Female (n = 10) Age 20-26 Mean Age 23.2	^#PROT ↑ vigor (POMS)	^§NA	^*NSE exercise performance ^#PROT ↑ blood CD4+/CD8+ cells	(Michalickova et al., 2016)Michalickova et al., 2016)
L. helveticus R0052 (n = 145), B. longum ssp. infantis R0033 (n = 147), B. bifidum R0071 (n = 142) capsule 3 × 10⁹ CFU Q.D. or placebo (n = 147) for 42 days	Double-blind Nonsmoking undergraduate students Exclusions: allergies, current cold, antibiotic use 2 months prior to study enrollment	Male (n = 210) Female (n = 371) Age 18-22 Mean Age 19.9	B. bifidum ↓ self-reported stress	^§NA	L. helveticus ↑ diarrhea B. bifidum ↓ diarrhea and incidence cold/flu B. bifidum interaction of stress and sleep ^*NSE BMI stress interaction	(Culpepper et al., 2016; Langkamp-Henken et al., 2015)
L. rhamnosus HN001 (n = 212) 6 × 10⁹ or placebo (n = 211) for 168 days post gestation and 168 days after birth	Double-blind English-speaking women at 14–16 weeks of gestation, breastfeeding Exclusions: medical problems related to pregnancy, age <16 years, planning to move outside the study center during study, probiotic use, subject or unborn child’s biological father had a history of asthma, hay fever, or eczema requiring medication	Female (n = 423) Mean Age 33.6	^#PROT ↓ depression (EPDS) and anxiety (STAI6)	^§NA	^§NA	(Slykerman et al., 2017)
B. animalis ssp. lactis-07 10⁹ CFU (n = 41), B. animalis ssp. lactis-07 2 × 10⁹ CFU + xylooligosaccharide 8g/d (n = 41), xylooligosacchari de 8g/d (n = 41), or maltodextrin placebo (n = 41) Q.D. for 21 days	Double-blind Crossover design Healthy adults, BMI 20–30 kg/m² Exclusions: physical or mental illness requiring medication or inpatient/outpatient treatment, planned major surgery, history of drug or alcohol abuse, severe allergies or a history of abnormal drug reaction, chronic GI complaints or GI drug use 4 weeks before enrollment, anti-inflammatory or prescription medication use, participation in an experimental drug trial 4 weeks before enrollment, participation in prebiotic or laxative trials within 3 months or use of antibiotics within 6 months of enrollment	Male (n = 22) Female (n = 22) Age 31–55 Mean Age 43	^#PROT ↓ self-reported happiness PRET ↑ self-reported vitality and happiness ^* NSE SYNT	^§NA	^NSE bowel function, plasma HDL, SCFA, Bifidobacterium, Bacteroides/Prevotella, Clostridium, Lactobacillus/Enterococcus/Atopobium*	(Childs et al., 2014)
S. boulardii Bioflor 2 × 10¹¹ CFU/capsule two capsules B.I.D. (n = 45) or placebo (n = 45) for 28 days	Double-blind Rome II IBS mixed or diarrhea predominant Exclusions: IBS constipation predominant, pregnant/lactating, chronic medical illness, history of abdominal surgery except appendectomy or hernia	Male (n = 44) Female (n = 46) Age 27-53 Mean Age 41.0	^*NSE dysphoria (IBS QOL)	^#PROT ↑ social functioning (IBS QOL)	^#PROT ↓ activity interference (IBS QOL)	(Choi et al., 2011)
1.31 high dose 1-3 × 10¹⁰ CFU (n = 28), low dose 3-6 × 10⁹ CFU Q.D.(n = 27), or placebo (n = 29) for 42 days	Double-blind Rome III IBS with diarrhea Exclusions: celiac disease, IBD, or antibiotic/probiotic use 4 weeks prior to enrollment	Male (n = 31) Female (n = 53) Age 20-70 Mean age 46.8	Low and high dose ^#PROT ↑ mental status (IBS QOL) Low and high dose ^#PROT ↓ gut specific anxiety	^§NA	^*NSE IBS symptoms	(Lorenzo-Zuniga et al., 2014)
L. acidophilus NCFM low dose 1 × 10⁹ (n = 112) high dose 1 × 10¹⁰ (n = 113) or placebo (n = 115) Q.D. for 84 days	Double-blind Rome III IBS Exclusions: Other GI disease or probiotic use within 3 months of enrollment	Male (n = 99) Female (n = 292) Age 18-65 Mean Age 47.9	Low and high dose ^#PROT ↓ anxiety (HADS) high dose ^#PROT ↓ depression (HADS)	^§NA	^#PROT ↓ pain for moderate to severe symptom groups	(Lyra et al., 2016)
S. cerevisiae CNCM I-3856 8 × 10⁹ CFU/g 1000 mg tablet Q.D. (n = 192) or placebo (n = 187) for 84 days	Double-blind Rome III IBS pain/discomfort ≥ 1 day/week, normal CRP and fecal calprotectin Exclusions: pregnancy, vegetarian, lactose intolerance, gluten sensitivity, antibiotic, antidepressant, opioid, narcotic, or chronic alcohol use	Male (n = 62) Female (n = 317) Age 18 to 75 Mean Age 45.3	^*NSE well-being (IBS-QOL)	^§NA	^#PROT ↓ bloating and pain for IBS constipated subgroup	(Spiller et al., 2016)
L. casei ssp. rhamnosus LCR35 2 × 10⁸ CFU T.I.D. (n = 25) or placebo (n = 25) for 28 days	Double-blind Rome III IBS Exclusions: current depression (HAM-D)	Male (n = 15) Female (n = 35) Age 34-59 Mean Age 47.1	^*NSE anxiety and depression (HAD)	^§NA	^#PROT ↓ IBS severity in diarrhea subgroup	(Dapoigny et al., 2012)
L. gasseri SBT2055 5 × 10⁸ CFU and B. longum SBT2928 1 × 10⁹ CFU in 100g yogurt with S. thermophilus and L. delbrueckii subsp. Bulgaricus (n = 115) or 100g placebo yogurt with S. thermophilus and L. delbrueckii subsp. bulgaricus (n = 109) Q.D. for 84 days	Double-blind Healthy Japanese volunteers Exclusions: history of significant medical illness, frequent intake of the test yogurt, diarrhea or viral syndrome within the past 30 days, current use of any prescribed medication, use of any other supplements during the trial, pregnancy, smoking > 20 cigarettes/day, drinking > 20 g alcohol/day, history of severe allergic reactions to food and medication	Male (n = 69) Female (n = 155) Age 32 to 76 Mean Age 53.9	^#PROT ↓ anxiety (GHQ-28)	^§NA	^#PROT ↓ NK cell activity, ACTH, salivary and serum cortisol (males only) ^*NSE CRP, IgG, IgE	(Nishihira et al., 2014)
L. gasseri CP2305 1 × 10¹¹ CFU T.I.D. (n = 17) or placebo (n = 17) for 28 days	Double-blind Rome III IBS Exclusions: organic GI diseases, severe systemic diseases, pregnant, lactating, history of significant abdominal surgery, severe endometriosis, neurological disorders, or dementia	Male (n = 15) Female (n = 19) Age 19-82 Mean Age 49.3	^#PROT ↓ health related worry (IBS-QOL)	^§NA	^#PROT ↓ Dorea, Enterococcus and Dialister genera	(Nobutani et al., 2017)
B. longum NCC3001 1 × 10¹⁰ CFU/g Q.D. powder (n = 22) or maltodextrin placebo (n = 22) for 42 days	Double-blind Rome III IBS mixed or diarrhea predominant and HAD score of 8-14 Exclusions: psychiatric disorder except anxiety or depression, antidepressant or anxiolytic use, probiotic use within 1 month or antibiotic use within 3 months of enrollment	Male (n=20) Female (n=24) Age 26-58 Mean Age 43.0	^#PROT ↓ depression (HAD-D) ^*NSE anxiety (HAD-A)	^#PROT ↓ amygdala, frontal, and temporal and ↑ occipital engagement in response to fearful stimuli ^*NSE SF-36 social function	^#PROT ↑ SF-36 physical ^*NSE constipation, diarrhea, or pain	(Pinto-Sanchez et al., 2017)
B. longum 2 × 10⁹ CFU (n = 31), 8g psyllium (n = 31), or B. longum + psyllium (n = 32) Bificolon, Nisshin Kyorin Pharmaceuticals Q.D. for 28 days	Double-blind UC mild or remitted w/out UC surgical history Exclusions: UC induction therapy or unstable prednisone or aminosalicylate dose 4 weeks before enrollment	Male (n = 39) Female (n = 55) Mean Age 36.0	^#PROT ↑ IBD QOL emotional	SYNT ↑ IBD QOL social	SYNT ↓ CRP SYNT ↑ IBD QOL greater than ^#PROT or PRET	(Fujimori et al., 2009)
Ecologic^® Barrier powder 2.5 × 10⁹ CFU/g Q.D. (n = 20) or placebo (n = 20) for 28 days	Triple-blind Nonsmoking adults Exclusion: Current mood disorder	Male (n = 8) Female (n = 32) Age 18-23 Mean Age 20.0	^#PROT ↓ rumination (LEIDS) ^#PROT ↓ aggressive thoughts ^*NSE BAI or BDI	^§NA	^§NA	(Steenbergen et al., 2015)
VSL#3 1.125 × 10¹¹ CFU (n = 57) or placebo (n = 48) Q.D. for 14 days	Double-blind Healthy students subjected to acute psychological stress Exclusions: diagnosed GI disorder, prior probiotic or current antibiotic use	Male (n = 36) Female (n = 69) Age 18–23 Mean Age 20.2	^*NSE stress (PASAT)	^*NSE (PASAT)	^*NSE heart rate, blood pressure (systolic or diastolic)	(Moller et al., 2017)
Fermented milk B. animalis ssp. lactis 1.25 × 10¹⁰, S. thermophilus 1.2 × 10⁹, L. bulgaricus 1.2 ×10⁹ L. lactis ssp. lactis (n = 12) CFU/cup, non-fermented milk B.I.D. (n = 11), or no probiotic milk drink (n = 13) for 28 days	Double-blind Healthy adults BMI 18-30 kg/m² Exclusions: GI or psychiatric symptoms	Female (n = 35) Age 18-55 Mean Age 36.5	^§NA	^#PROT ↓emotion task response in affective, viscerosensory, somatosensory cortices	^§NA	(Tillisch et al., 2013)
100g Yogurt with L. acidophilus LA5 and B. lactis BB-12 1 × 10⁷ CFU + one placebo capsule (n = 25); one probiotic capsule L. casei 3 × 10³, L. acidophilus 3 × 10⁷, L. rhamnosus 7 × 10⁹, L. bulgaricus 5 × 10⁸, B. breve 2 × 10¹⁰, B. longum, S. thermophilus 3 × 10⁸ (CFU/g), and fructooligosaccharide 100mg + conventional yogurt 100g Q.D.(n = 25); or conventional yogurt 100g + one placebo capsule (n = 20) for 42 days	Double-blind Petrochemical workers without chronic illness Exclusions: antibiotic, vitamin, or supplement use	Male (n = 36) Female (n = 34) Age 20–60 Mean Age 40.0	^#PROT yogurt and capsule ↓ depression and anxiety (DASS) ^#PROT yogurt and capsule ↓ GHQ scores	^§NA	^*NSE plasma Tryptophan, Cortisol, ACTH or Neuropeptide Y levels	(Mohammadi et al., 2016)
L. helveticus R0052 and B. longum R0175 3 × 10⁹ CFU Q.D. (n = 26) or placebo (n = 29) for 30 days	Double-blind Healthy Caucasian adults Exclusions: neurological, psychiatric, renal, hepatic, cardiovascular and respiratory diseases, pregnancy, food allergy, clinical trial participation within two months of study enrollment, psychotropic drug or stimulating nutritional supplements (vitamin C), ginger, guarana, ginseng, dehydroepiandrosterone, melatonin, antioxidants, anxiolyics, antidepressants, selenium, narcotics, replacement hormoes, more than 5 cups of coffee or tea/d, 0.2 liters of cola, 30–40 g of chocolate, three glasses of wine, or two fermented dairy products, or smoking >20 cigarettes	Male (n = 14) Female (n = 41) Age 30-59 Mean Age 42.8	^#PROT ↓ depression (HADS-D) and anxiety (HADS-A) ^#PROT ↓ psychological distress (HSCL-90) ^#PROT ↓ stress (PSS) in patients with low urinary cortisol	^§NA	↓ Urinary cortisol See Table 2 for outcomes in rats	(Messaoudi et al., 2011a; Messaoudi et al., 2011b)
L. acidophilus Rosell-52 and B. longum Rosell-175 3 × 10⁹ CFU Q.D. (n = 37) or placebo (n = 38) for 21 days	Double-blind Healthy subjects experiencing 2 or more daily stress symptoms (anxiety, nervous, irritable, sleeping problems, GI disturbance) for 30 days prior to enrollment	Male (n = 21) Female (n = 54) Age 27-49 Mean age 38.0	^*NSE psychological stress ^#PROT ↓ stress induced abdominal pain and nausea	^§NA	^§NA	(Diop et al., 2008)
L. helveticus R0052 and B. longum R0175 3 × 10⁹ CFU Q.D. (n = 40) or placebo (n = 39) for 56 days	Double-blind ⩾11 on the QIDS-SR16 or ⩾14 on the DASS-42, age > 16 Exclusions: medical disorder, pregnant or lactating, antidepressant use, suicide or violence risk, probiotic, antibiotic, or psychotropic medication use 4 weeks prior to trial	Male (n = 17) Female (n = 62) Mean Age 35.0	^*NSE depression or anxiety (MADRS, QIDS-SR16, DASS)	^§NA	^*NSE iCGI-SiCGI-I, GAF, CRP, IL-6, TNF-α, IL-1β	(Romijn et al., 2017)
L. acidophilus, L. casei, and B. bifidum Tak Gen Zist Pharmaceutical Company (2 × 10⁹ CFU/g Q.D. (n = 20) or placebo (n = 20) for 56 days	Double-blind DSM-IV diagnosis Major Depressive Disorder	Male (n = 6) Female (n = 34) Age 20-55 Mean Age 37.3	^#PROT ↓ depression (BDI) ^#PROT ↓ anxiety (BAI)	^§NA	^#PROT ↓ HOMA-IR ^#PROT ↓ CRP ^#PROT ↑ glutathione	(Akkasheh et al., 2016)
S. thermophilus SGst01, B. animalis ssp. Lactis SGB06, S. thermophiles, B. bifidum SGB02, L. delbrueckii ssp. Bulgaricus DSM20081, L. acidophilus SGL11, L. plantarum SGL07, L. reuteri SGL01 1.5 × 10¹⁰ CFU each in corn maltodextrin, silica, casein, lactose, and gluten (n = 24) or placebo (n = 24) Q.D. for 21 days	Double-blind Crossover design normal weight lean, normal weight obese, pre-obese/obese groups BMI range 19.5 – 30 kg/m²	Female (n = 48) Age 27-56 Mean Age 34.6	^#PROT ↓ depression (SCL90R) in normal weight lean ^#PROT ↓ anxiety (SCL-90R) in pre-obese/obese	^#PROT ↓ avoidance (BUT) ^*NSE social insecurity, interpersonal distrust, interceptive awareness (EDI-2)	^#PROT ↓ psychotic symptoms (SCL-90R) in normal weight obese and pre-obese/obese	(De Lorenzo et al., 2017)
L. acidophilus, L. casei, B. bifidum, and L. fermentum Tak Gen Zist Pharmaceutical Company 2 × 10⁹ CFU/g each Q.D. (n = 30) or placebo (n = 30) for 84 days	Double-blind McDonald RRMS Exclusions: pregnant or lactating, probiotic or prebiotic use prior to trial enrollment	Male (n = 10) Female (n = 50) Age 18-55 Mean Age 34.1	^#PROT ↓ depression and anxiety symptoms (BDI, GHQ, DASS)	^§NA	^#PROT ↓ insulin, NO, CRP, MDA, HOMA-IR, HOMA-B ^#PROT ↑ QUICKI, HDL	(Kouchaki et al., 2016)
Lacidofil^® 2 × 10⁹ CFU (n = 28) or placebo (n = 32) B.I.D for 84 days	Double-blind Stage 2 or 3 colorectal cancer age > 20, completed treatments between 6 weeks and 2 years prior to enrollment Exclusions: histories of other cancers, colostomies, probiotic consumption, physical or mental disability, chronic diseases, antibiotic use, pregnancy, abnormal liver function, kidney function, or blood cell counts	Male (n = 35) Female (n = 25) Age 45-67 Mean Age 56.2	^*NSE emotional well-being (FACT-EWB) ^#PROT ↓ anxiety and depression (PHQ-9 within group only–NSE between groups)	^*NSE social well-being (FACT-SWB)	^#PROT ↓ bowel symptoms, functional well-being, cancer related FACT	(Lee et al., 2014)
Bifidobacterium combined with fructooligosaccharide CFU not reported (n = 63) or placebo (n = 62) for 60 days	Double-blind HE - West haven grade 1 or 2 hepatitis B (n = 35), hepatitis C (n = 70), or cryptogenetic cirrhosis (n = 20) venous ammonia >50 mmol/L Exclusions: West haven grade 3+, alcoholism, diabetes mellitus	Male (n = 62) Female (n = 63) Mean Age 50.1	^§NA	^#PROT ↓ TMT A and B times, ^#PROT ↑ Symbol Digit Modalities and Block Design Test	^#PROT ↓ blood ammonia levels	(Malaguarnera et al., 2010)
L. rhamnosus GG (n = 14) or placebo (n = 16) 5.5 × 10¹⁰ CFU B.I.D. for 56 days	Double-blind Cirrhosis with minimal hepatic encephalopathy Exclusions: alcohol use within 6 months, upper GI bleeding or systemic antibiotics within 6 weeks, current or past treatment for HE, hepatocellular cancer, yogurt/probiotic consumption within 2 weeks, inflammatory bowel disease, history of pancreatitis, psychoactive medication use except anti-depressants, recent absolute neutrophil count <500/mm3 and liver transplant	Male (n = 25) Female (n = 12) Age 47-65 Mean Age 57.4	^§NA	^#PROT ↑ SIP social function ^*NSE digit symbol or block design tests	^#PROT ↓ Enterobacteriaceae abundance ^#PROT ↓ Clostridiales Incertae Sedis XIV and Lachnospiraceae abundance	(Bajaj et al., 2014)
L. rhamnosus JB-1 1 × 10⁹ CFU (n = 29) or placebo (n = 29) capsules Q.D. for 56 days	Blinding status not reported Crossover design Healthy adult (n = 29) Exclusions: acute or chronic illness, neuropsychiatric disorder (MINI), immunodeficiency, bleeding disorder, color blindness, dyslexia, dyscalculia, experimental drug trial participation, diet, probiotics, antibiotics, antipsychotics, anxiolytics, laxatives, enemas, anti-coagulants NSAIDS, antidepressants or consumption of any psychotropic medication	Male (n = 29) Age 20-33 Mean Age 24.6	^*NSE stress, anxiety, depression (PSS, BDI, BAI, STAI, SECPT, Pittsburgh sleep quality index)	^*NSE PAL, AST, RVIP, emotional Stroop or recognition task	^*NSE IL-1β, IL-6, IL-8, IL-10, TNF-α	(Kelly et al., 2017)
C. butyricum 420 mg capsule 1.0 × 10⁷ CFU/g B.I.D. 14 days until one day before surgery (n = 10) or placebo (n = 10)	Blinding status not reported may be single-blind Cancer patients scheduled for laryngectomy	Male (n = 10) Female (n = 10) Age 45-67 Mean 56.075	^#PROT ↓ anxiety (HAM-A)	^§NA	^#PROT ↓ serum CRF and heart rate before surgery	(Yang et al., 2016b)
L. acidophilus ATCC4356 1.25 × 10⁹ CFU B. longum ATCC15707 1.35 × 10⁹ CFU in vitamin supplement T.I.D. (n = 20) or vitamin supplement without ^#PROT (n = 20) for 56 days	Blinding Status not reported Irritable Eye Syndrome Exclusions: IBS, systemic, or neuropsychiatric disease	Groups matched by sex (n = 40) Age 39-53 Mean Age 45.5	^#PROT ↓ anxiety and depression (HAD)	^§NA	^#PROT ↓ WBC, monocyte, IL-6, and TNF-α	(Feher et al., 2014)
L. rhamnosus GG and B. lactis BB-12 1 × 10⁹ CFU (n = 33) or placebo (n = 32) Q.D. for 98 days	Blinding status not reported DSM-IV schizophrenia or schizoaffective outpatient, PANSS positive ≥ 1 and/or negative ≥ 4 or total ≥ 50, with at least 3 positive or negative items with scores ≥3 at screening, no antipsychotic medication changes within 21 days of enrollment Exclusions: mental retardation, celiac or medical disorder, DSM-IV substance abuse within 3 months, drug trial within 30 days of study enrollment, pregnant or lactating, antibiotic use within 14 days of enrollment	Male (n = 42) Female (n = 23) Age 18-65 Mean Age 46.3	^*NSE PANSS general, negative, or positive symptoms	^§NA	^#PROT ↓ symptoms in presence of C. albicans antibodies ^#PROT ↓ constipation	(Dickerson et al., 2014; Severance et al., 2017; Tomasik et al., 2015)

Abbreviations:

^§

NA = Not assessed,

NSE = No significant effect of probiotic treatment,

PROT = Probiotic Treatment, ACTH = Adrenocorticotropic hormone, ADHD = Attention Deficit Hyperactivity Disorder, ASD = Autism Spectrum Disorder, AST = Attention Switching Task, ATCC = American Type Culture Collection, BAI = Beck Anxiety Inventory, BDI = Beck Depression Inventory, BDNF = Brain Derived Neurotropic Factor, BES = Binge Eating Scale, B.I.D = Twice a day, BMI = Body Mass Index, BSID-II-MDI = Bayley Scale Infant Development-II-Mental Development Index, BSID-II-PDI = Bayley Scale Infant Development-II-Psychomotor Development Index, BUT = Body Uneasiness Test, CFU = Colony Forming Units, CNCM = Collection Nationale de Cultures de Microorganismes, CRF = Corticotrophin Releasing Factor, CRP = C-Reactive Protein, DASS = Depression and Anxiety Stress Scale, DSM = Deutsche Sammlung von Mikroorganismen, DSM-IV = Diagnostic and Statistical Manual for Mental Disorders – IV, Ecologic^® Barrier = B. bifidum W23, B. lactis W52, L. acidophilus W37, L. brevis W63, L. casei W56, L. salivarius W24, and L. lactis W19 and W58, EDI-2 = Eating Disorder Inventory – 2, EPDS = Edinburgh Postnatal Depression Scale, EQ-5D-5L = European Quality of Life, FACT-EWB = Functional Assessment of Cancer Therapy-Emotional Well-being, FACT-SWB = Functional Assessment of Cancer Therapy-Social Well-being, GAF = Global Assessment of Functioning, GDS-SF = Geriatric Depression Scale – Short Form, GHQ = General Health Questionnaire, GI = Gastrointestinal, GMMS = Gastrointestinal motility modulating substances, GSRS = Gastrointestinal Symptom Rating Scale, HADS = Hospital Anxiety and Depression Scale, HAM-A = Hamilton Anxiety Scale, HAM-D = Hamilton Depression Scale, HDL = High Density Lipoprotein, HE = Hepatic encephalopathy, HSCL-90 = Hopkins Symptom Checklist, hs-CRP = high-sensitivity C-reactive protein, HOMA-IR = Homeostatic Insulin Resistance, HOMA-B = Homeostatic Beta cell Function, IBD = Inflammatory Bowel Disease, IBS = Irritable Bowel Syndrome, I.31 = L. plantarum CECT7484 + CECT7485 and P. acidilactici CECT7483, iCGI-I = improved Clinical Global Impression Scale-Improvement, iCGI-S = improved Clinical Global Impression Scale-Severity, IgE = Immunoglobulin E, IgG = Immunoglobulin G, IL-1β = Interleukin-1- beta, IL-6 = Interleukin 6, IL-8 = Interleukin 8, IL-10 = Interleukin 10, IV = Intravenous, Lacidofil^® = 95% L. rhamnosus R0011 & 5% L. helveticus R0052, LEIDS = Leiden Index of Depression Sensitivity, MDA = Malondialdehyde, MADRS = Montgomery-Asberg Depression Rating Scale, MINI = Mini-International Neuropsychiatric Interview, NK = Natural Killer, NO = Nitric Oxide, NSAID = Non-Steroidal Anti-Inflammatory Drug, PAL = Paired Associative Learning, PANSS = Positive and Negative Syndrome Scale, PASAT = Paced Auditory Serial Addition Test, Ped = Pediatric, PHQ-9 = Patient Health Questionnaire-9, P.O. = Per Oral, POMS = Profile of Mood States, PPI = Proton Pump Inhibitors, PRET = Prebiotic Treatment, PSS = Perceived Stress Scale, Q.D. = One a day, Q.I.D. = Four times a day, QIDS-16 = Quick Inventory of Depression Symptomatology, QOL = Quality of Life, QUICKI = Quantitative Insulin Sensitivity Check Index, RRMS = Relapse Remitting Multiple Sclerosis, RVIP = Rapid visual information processing, SCFA = Short Chain Fatty Acids, SCL90R = Symptom Checklist Revised, SECPT = Socially Evaluated Cold Pressor Test, SIP = Sickness Impact Profile, SSP = subspecies, STAI = State Trait Anxiety Inventory, SYNT = Synbiotic Treatment, T.I.D. = Three times a day, TMT = Trail Making Test, TNF-α = Tumor Necrosis Factor-alpha, UC = Ulcerative Colitis, VLDL = Very Low-Density Lipoprotein VSL#3 = S. thermophilus DSM 24731, B. longum DSM 24736, B. breve DSM 24732, B. infantis DSM 24737, L. acidophilus DSM 24735, L. plantarum DSM 24730, L. paracasei DSM 24733, L. delbrueckii ssp. bulgaricus DSM 24734, WBC = White Blood Cell