Table 1.

Associations between natural/experimentally-altered microbiomes and cognitive tasks. All studies were performed on mice, except for one on human infants [16] and one on human adults [17]. Conventionally colonized (CC) refers to mice born with natural microbiome, germ-free (GF) refers to mice born and kept free of any microbes and housed in sterile isolators, and ex-germ free (ex-GF) refers to mice born free of microbes and housed with CC mice post-weaning (three weeks old) to facilitate recolonization of microbes. Cognitive/behavioural results indicate if differences are significantly greater (>), significantly less (<) or non-significant (=). Neurological results are a brief overview and readers are referred to original papers for further details. BDNF, brain derived neurotrophic factor; OTUs, operational taxonomic units.

microbiome treatment	cognition/behaviour assay method	cognitive/behaviour assay result	neurological/physiology assays results	reference
germ free (GF), recolonized (ex-GF) and conventionally colonized (CC)	choice of empty versus social chamber interactions with novel versus familiar mice food-preference test following demonstrator observation	chamber sociability: GF < CC = ex-GF social recognition: GF and ex-GF < CC social observation of demonstrator: GF < CC = ex-GF social information transfer: GF = ex-GF = CC	—	[18]
GF, ex-GF and CC	cued fear conditioning (tone + shock in experimental context (i.e. box))	acquisition: GF = ex-GF = CC cue recall: GF < ex-GF = CC context recall: GF = CC = ex-GF extinction: GF < CC; ex-GF < CC	genome-wide RNA sequencing of amygdala shows altered gene expressions	[19]
GF, CC, CC-pathogen infected (CC-in), CC-in with probiotics (CC-in-pro)	light–dark box novel object recognition T-maze tests performed following exposure to acute stress (AS) or no stress (NS)	anxiety: CC-in = CC; GF = CC recognition and working memory (NS): CC-in = CC; GF < CC recognition and working memory (AS): CC-in < CC; GF < CC object and working memory (NS): CC-in-pro = CC-in object and working memory (AS): CC-in-pro > CC-in	differences in corticosterone and hippocampal BDNF and c-Fos	[10]
anxious mouse strains fed different Bifidobacteria probiotics: B. longum and B. breve	object recognition task Barnes maze cued fear conditioning	recognition memory: B. longum and B. breve > control mice spatial learning: B. longum = control = B. breve spatial memory: B. longum > control; B. breve = control fear conditioning learning and memory to context: B. longum and B. breve = control fear conditioning memory to cue and extinction: B. longum = control = B. breve	no difference in basal corticosterone across treatment groups	[20]
microbiome manipulation through restricted diets: high fat (hf), high sugar (hs), normal chow (nc)	step-down latency and open field test novel object recognition/location Morris water maze	anxiety and recognition memory: hf = hs = nc long-term spatial memory: hs < hf = nc reverse learning: hs = hf < nc	—	[21]
beef (b) versus normal chow (nc) diet	novel apparatus neophobia hole-board box	anxiety: b < nc working memory: b > nc spatial memory: b > nc	—	[9]
high fat transplanted microbiome (hft), normal chow transplanted microbiome (nct)	elevated plus and open field assays cued fear conditioning	anxiety: hft > nct cue acquisition, memory and extinction: hft < nct context memory: hft = nct	differences in protein expression in brain (e.g. BDNF)	[7]
CC, antibiotic-treated (Abx), + exercise (exc), + probiotics (pro), + CC faecal transplant (ft)	novel object recognition	short-term memory: no difference across groups long-term memory: Abx and Abx-ft < CC Abx-exc and Abx-pro = CC CC-exc and CC-pro = CC	differences in neurogenesis across treatment groups	[22]
CC, antibiotic-treated (Abx)	object recognition task Barnes maze	recognition memory: Abx < CC spatial learning and memory: Abx = CC	differences in protein and receptor expression in hippocampus, amygdala and hypothalamus	[23]
OTUs from gut microbiome	open field assay and light/dark box cued fear conditioning	bacterial OTUs identified as either positively or negatively associated with anxiety and context memory	—	[24]
natural variation in microbiome age 1 (quantified as clusters of microbial taxa and diversity indexes)	Mullen Scales of Early Learning at age 1 and age 2	higher scores associated with high levels of Bacteroides rather than high levels of faecalibacterium. High microbiome diversity associated with poor scores on visual reception, expressive and receptive language skills at age 2	higher microbiome diversity associated with larger left precentral gyrus, left amygdala and right angular gyrus at age 2	[16]
biopsied colon microbiome from patients with cirrhosis of the liver	psychometric test batteries for psychomotor speed, vasomotor coordination, attention, set shifting and inhibitory control	bacterial OTUs identified as either positively or negatively associated with cognitive performance across cognitive tests	bacterial OTUs identified as either positively or negatively associated with liver inflammation	[17]