TABLE 1.
Brief description of studies indicating a link between the gut microbiota and the hippocampus.
| Topic | Number of studies | Experimental model | Intervention | Findings |
| Learning and memory (12 studies) | (7 studies) | Probiotic treated animals | Streptococcus thermophilus, Akkermansia muciniphila, Porphyromonas gingivalis, Streptococcus faecalis, Bacillus mesentericus | Restored impaired learning and memory |
| (1 studies) | Gut microbiota disrupted animals | Antibiotic therapy | Impaired learning and memory | |
| (3 studies) | Fecal microbiota transplantation From schizophrenic people, animals under high fat diet regimen and chronic unpredictable stress | Impaired learning and memory | ||
| (1 study) | Fecal microbiota transplantation from aged people | Impaired learning and memory in recipients | ||
| Synaptic plasticity (15 studies) | (7 studies) | Probiotic treated animals | Different species of Lactobacilli and Bifidobacteria, Streptococcus salivarius | Enhanced LTP |
| (2 studies) | Improved synaptic plasticity | |||
| (1 study) | Decreased LTP | |||
| (5 study) | Gut microbiota disrupted animals | Fecal microbiota transplantation from aged donor | Reduced expression of proteins involved in synaptic plasticity, reduces glutamatergic currents, dendritic signaling, intrinsic excitability of hippocampal neurons | |
| Dysbiosis | ||||
| BDNF level in hippocampus (27 studies) | (20 studies) | Probiotic treated animals | Different species of Lactobacilli and Bifidobacteria, Streptococcus thermophilus, Enterococcus faecium, Clostridium butyricum, Streptococcus salivarius | Increased the level of BDNF in the hippocampus |
| (2 studies) | No change in BDNF level | |||
| (1 study) | Gut microbiota disrupted animals | Fecal microbiota transplantation From aged donors | Reduced hippocampal expression of BDNF | |
| (4 studies) | Antibiotic therapy | Decreased hippocampal BDNF | ||
| Inflammatory/anti-inflammatory balance (37 studies) | (2 studies) | Probiotic treated animals | Different species of Lactobacilli and Bifidobacteria, Akkermansia muciniphila, Porphyromonas gingivalis, Mycobacterium vaccae, Streptococcus thermophiles, Agathobaculum butyriciproducens, Escherichia coli | Attenuate inflammation |
| (1 study) | Reduces expression of inflammatory cytokines | |||
| (1 study) | Decreases microglial activation- induced inflammation | |||
| (4 studies) | Suppresses NF-κB activation | |||
| (10 studies) | reduces TNF-α expression | |||
| (5 studies) | Decreases expression of the proinflammatory interleukin IL- 1β | |||
| (5 studies) | Decreases expression of the proinflammatory interleukin I L- 6 | |||
| (1 studies) | Increased the anti-inflammatory interleukin IL-10 | |||
| (1 study) | Gut microbiota disrupted animals | Gut microbiota metabolite, TMAO | Increases proinflammatory cytokine expression | |
| (1 study) | Increases microglia-mediated neuroinflammation | |||
| (1 study) | Antibiotic therapy | Decreased proinflammatory cytokines IFN-γ and IL-17A levels and increased anti-inflammatory cytokine IL-10 and Increased hippocampal TNF-α and IL-1β | ||
| (1 study) | Increased the recruitment of microglia and monocytes to the hippocampus and induced NF-κB activation and IL-1β, IL-6 and TNF-α expression in the brain | |||
| (1 study) | Fecal microbiota transplantation from chronic mild stress treated animals | Increased IL-6 and TNF-α | ||
| (1 study) | Fecal microbiota transplantation From aged subjects | Increased levels of pro- inflammatory cytokines in hippocampus | ||
| (1 study) | Fecal microbiota transplantation from AD patients | Increased levels of inflammatory factors in both peripheral blood and the hippocampus | ||
| (1 study) | Germ free animals | Enhanced levels of IL-2, IL-4 IL-6, IL-10, IL-17A and TNF-α in hippocampus and decreased IL- 4 | ||
| Oxidant and anti-oxidant factors (18 studies) | (1 studies) | Probiotic treated animals | Different species of Lactobacilli and Bifidobacteria, laccoccus, Clostridium butyricum, Enterococcus faecium, Streptococcus faecalis, Bacillus mesentericus | Reduced hippocampal oxidative stress |
| (5 studies) | Attenuated oxidative enzymes | |||
| 4 studies) | Increases antioxidant activity | |||
| (4 studies) | Increased antioxidant/oxidant ratio | |||
| (1 studies) | Gut microbiota disrupted animals | Gut microbiota metabolite, TMAO | Promote oxidative stress in the hippocampus | |
| (2 studies) | Decreased antioxidant activities in the hippocampus | |||
| (1 studies) | From Fecal Microbiota transplantation | Increased level of oxidative stress | ||
| Pathological changes (3 studies) | (4 studies) | Probiotic treated animals | Different species of Lactobacilli, Clostridium butyricum | Attenuated the histopathological changes in the hippocampus |
| Apoptosis (9 studies) | (2 studies) | Probiotic treated animals | Different species of Lactobacilli and Bifidobacteria, Streptococcus Thermophilus, Lactococcus lactis, Clostridium butyricum | Decreased concentrations of the apoptotic agents Bax and cleaved caspase-3 |
| (3 studies) | Increased expression of anti- apoptotic genes (Bcl-2) in the hippocampus | |||
| (3 studies) | Suppressing hippocampal apoptosis | |||
| (1 studies) | Gut microbiota disrupted animals | Antibiotic therapy | Increased population of apoptotic neuron cells | |
| Amyloid beta plaque (8 studies) | (8 studies) | Probiotic treated animals | Different species of Lactobacilli and Bifidobacteria | Reduces deposition of Aβ in the hippocampus |
BDNF, brain derived neurotrophic factor; LTP, long term potentiation; TMAO, trimethylamine N-oxide.