Table 2.

Summary of studies investigating links between stress and the gut microbiota. Microbiota which show an association (not necessarily causality) with stress-resilience and stress-sensitivity are indicated in the columns labeled SR and SS, respectively. This depends on the study but may mean, e.g., a probiotic supplement which increased stress-resilience, or an increase in relative abundance of the microbiota in stress-resilient individuals. Abbreviations: EPM, Elevated Plus Maze; FST, Forced Swim Test; TST, Tail Suspension Test; HbA1c, Hemoglobin A1c; IL, Interleukin; IFN-γ, Interferon gamma; LDB, Light-Dark Box; OFT, Open Field Test; NOR, Novel Object Recognition; MSS, Maternal Separation Stress.

Study Design (Stress, Subjects, Intervention)	Results	SR	SS	Reference
FST BALB/c mice (M, adult) Probiotic Lactobacillus rhamnosus JB-1, 28 days prior to FST/Vagotomy	Increase in anxiety-like (EPM) and depressive like behaviour (FST). Both ameliorated by probiotic Stress-induced increase in corticosterone ameliorated by probiotic. Stress-induced hyperthermia not affected by probiotic. Vagotomy prevented the anxiolytic effects of the probiotic. Changes in gut microbiota not reported	Probiotic: L. rhamnosus JB-1	Not applicable	[36]
Chronic mild stress, 7 w C57BL/6J Mice (M, 7 w) Probiotic: Lactobacillus reuteri ATCC 23272, 2 w during stress and 2 w post-stress	Increase in depression-like behaviour (FST): prevented by probiotic. Increase in serum kynurenine following stress. Prevented by probiotic. Inhibition of the enzyme IDO1 by Lactobacillus-produced reactive oxygen species (H202) in vivo Decreased (fecal) class Bacillus, specifically genera Lactobacillus and Turicibacter	Probiotic: L. reuteri ATCC 23272	Decrease in (fecal) Lactobacillus	[15]
Grid floor stress, 15 d BALB/c mice (F, 5 w) No intervention	Increase in anxiety-like (triple test) and depressive-like behaviour (TST) Lower blood glucose but highter HbA1c were found. Cytokines were reduced in the control mice but not the stressed mice. Correlations were found between IL-6, IFN-γ, and behavior in the LDB, EPM, and OFT. Increase in (cecal) Odoribacter, Alistipes and an unclassified genus from the Coriobacteriaceae family. Lachnospiraceae correlated to risk assessment behaviors. Bacterioides correlated with immobility in TST; Ruminococccaceae correlated to entries to closed arms in triple test (anxiety/activity)	Not applicable	Bacterioides; Ruminococccaceae	[12]
MSS, 15 d Sprague Dawley rats, sex not stated, 4 d neonatal Probiotic L. rhamnosus strain R0011 (95%) and L. helveticus strain R0052 (5%), 15 d during stress	Behaviour not measured Increase in serum cortisol and gut permeability. Prevented by probiotic Decrease in genus Lactobacillus. Increase in bacterial adherence and penetration into mucosal cells. Increases in cortisol, gut permeability, and bacterial adherence/penetration was prevented by probiotic supplementation.	Probiotic: L. rhamnosus strain R0011 (95%) and Lactobacillus helveticus strain R0052 (5%)	Not applicable	[59]
MSS, 15 d Sprague Dawley rats (M, 90 d) Probiotic Bifidobacterium infantis 35624, 45 days	Increase in depressive-like behviour (FST), ameliorated by probiotic supplementation No difference in plasma corticosterone, L-kynurenine, tryptophan or kynurenic acid. An increase in IL-6 following stimulation with immune stimulant concanavalin A was prevented by the probiotic Gut microbiota not measured	Probiotic: B. infantis 35624	Not applicable	[40].
MSS, 10 d Sprague Dawley rats (M, 7–8 w) No intervention	Increased stress-induced faecal boli number in the OFT, but no changes in behavior Increased plasma corticosterone and increased systemic immune response in response to in vitro LPS challenge. Decreased pain threshold Change in microbiota structure (taxa not specified)	Not applicable	Not applicable	[16]
MSS, 1 w Infant rhesus monkeys (M+F, 6–9 m) No intervention	Decrease in total abundance of fecal bacteria and Lactobacillus by day 3, but back to normal after a week	Not applicable	Not applicable	[67]
Prenatal stress Human infants No intervention	Gastrointestinal symptoms more common in babies from mothers who reported higher stress. Cortisol and stress related questionnaires did not correlate in the mothers. Increased fecal Escherichia-enterobacteria and lower lactic acid bacteria and Actinobacteria	Not applicable	Not applicable	[69]
Prenatal (dam exposed to CMS) Offspring of pregnant C57BL mice exposed to CMS stress No intervention	Behavior not measured Increased fecal Rikenellaceae and Odoribacter, Mucispirillum and a decrease in Bacteroides	Not applicable	Not applicable	[66]
Prenatal (dam exposed to restraint stress) Offspring of pregnant C57/B16 mice No intervention	Offspring showed increase in anxiey-like behvior (EPM, NOR) in adulthood Increased plasma IL-1β in placenta and fetal brains but did not persist till adulthood. Decreased BDNF found in maternal placenta and in brains of adult offspring. Microbial community composition clustered differently in the stress group from control in both pregnant dams and their offspring	Not applicable	Not applicable	[65]
Restraint Stress (16 h/d × 7 d) Swiss Webster & CD-1 mice (M, 6–8 w) Fecal transplant from stressed mice to germ free mice	Behaviour not measured Increased inflammatory response to colonic pathogen in germ free mice with fecal transplant from stressor exposed mice. Increased (fecal) Firmicutes and decreased Actinobacteria and Bifidobacterium.	Not applicable	Not applicable	[63]
Restraint Stress (6 h/d × 3 w) Sprague Dawley rats (M, 220–240 g) Probiotic: L. helveticus ns8, 26 d	Increased depressive-like behavior (SPT) and anxiety-like behavior (EPM, OF). Body weight was reduced. Increase in plasma corticosterone and pro-inflammatory cytokines TNF-α and IFN-γ and decrease in plasma IL-10. Decreased BDNF in the hippocampus, prevented by probiotic Stress-induced changes in behaviour, corticosterone, IL-10, BDNF were prevented by the probiotic supplementation Gut microbiota not measured	Probiotic: L. helveticus ns8	Not applicable	[41]
Restraint stress, 12 h/d × 7 d CD1 mice (M, 8 w) No intervention	Behaviour not measured Increased TNF-α gene expression in colonic tissue Total bacteria and Gram negative bacteria increased in small intestine, cecum, and large intestine. Decrease in bacterial diversity and richness. Reduced family Porphyromonadaceae, specifically genus Tannerella. Increased colonization by introduced pathogen Citrobacter rodentium	Not applicable	Not applicable	[60]
Restraint Stress, 15 h/d × 7 d CD-1 mice (M, 6–8 w) No intervention	In the (colonic) mucosca-associated bacteria, a decrease in the families S24-7 and Lactobacillaceae and genera Lactobacillus spp., were found, and in an increase in the family Ruminococcaceae, and genera Oscillospira. In the luminal bacteria, a decrease in the family S24-7, as well as genera Adlercreutzia, and an unclassified genus in S24-7 were found	Not applicable	Not applicable	[13]
Restraint stress/FST alternated, 19 days CF-1 mice (M+F, 6 w)	Distance travelled in EPM and LDB increased, increased rearings in OF. Blood collected after behavioral tests Males had higher corticosterone levels following acute stress (behavioral testing) Increase in family Lachnospiraceae. Decrease in genus Sarcina only in females. Ruminococcus gnavus increased in females but decreased in males	Not applicable	Not applicable	[58]
Social stress: cage in cage aggressor CD1 and C57BL/6 mice (M, 6–8 w)	Behaviour not measured No difference in colonic cytokines Decrease in relative abundance of families Porphyromonadaceae and Lactobacilliaceae, and genera Lactobacillus, Parabacteroides, and an unclassified genus from phylum Firmicutes and unclassified genus from class Bacilli. The absolute abundance of lactobacilli was also reduced, specifically L. reuteri, but only in the outbred CD-1, not the inbred C57BL/6 mice	Not applicable	Not applicable	[56]
Social stress: chronic social defeat C57BL/6 mice (M, 8 w)	Decrease in social interaction Increase in (fecal) genus Bifidobacterium in the stress resilient group. Not detected in the control group or stress-sensitive group	Bifidobacterium	Not applicable	[62]
Social stress: resident intruder, 6 h/d × 10 d C57BL/6J male, juvenile (5–6 wk)	Behaviour not measured Differed across time points. Key changes were a decrease in phylums Bacteroidetes, Firmicutes, Verrucomicrobia; and genera Oscilospira and Anaeroplasma, with a trend in decrease in Lactobacillus. An increase and decrease in Akkermansia were found at different time points. A trend of increase in phylum Proteobacteria was found	Not applicable	Not applicable	[57]
Social stressor (6 d × 2 h/d) CD1 Mice (M, 8 w) Antibiotics (ampicillin (1 mg/mL), vancomycin (0.5 mg/mL), neomycin sulfate (1 mg/mL), and metronidazole (1 mg/mL))	Behaviour not measured Increase in proinflammatory markers, particularly IL-6, prevented in antibiotic group Immediately after induced stress, the (cecal) microbiome of mice had consistently altered within the group, and clustered separately from the control group, but after 15 h, the separation was no longer as clear, with variation within the stress group.Within genera, decrease in Bacteroides,increase in Clostridium, trend of decrease in Lactobacillus Stress-induced increases in plasma IL-6 was inversley correlated with relative abundances of genera Coprococcus, Pseudobutyrivibrio and positively correlated with Dorea	Not applicable	Not applicable	[11]
Water Avoidance Stress (1 h/d × 7 d) C57BL/6N mice (F, 6 w) Antibiotics during stress (Bacitracin A, Neomycin, Amphotericin B)	Pain related behavior in response to intracolonic capsaicum increased. Slightly mitigated with antibiotics. Increased fecal pellet output, plasma corticosterone, and adrenal gland weight. Increased luminal s-IgA levels. In the colon tissue, cannabanoid receptors increased marginally, and tryptophan hydroxylase (TPH1) expression increased by 40% Antibiotics and stress enhanced bacterial adherence to luminal wall. Fecal Clostridium coccoideds cluster XIVa was increased, and Verrucobactera, Lactobacillus and Enterococcus spp. decreased	Not applicable	Not applicable	[190]