Table 1.
Clinical and pre-clinical findings of the alterations of A. muciniphila in several neuropsychiatric disorders.
| Neuropsychiatric disorder | Experimental subjects | Intervention | Major findings | References |
|---|---|---|---|---|
| Depression | Social defeat stress mouse model | 16S rRNA gene V3-V4 regions sequencing | •Altered gut microbiota: ↓A. muciniphila, Ruminococcus, unclassifed Mollicutes, Paraprevotella, Dorea ↑Oscillospira, Bacteroides, Lachnospiraceae •Akkermansia a correlate with behavioral metrics |
(Mcgaughey et al., 2019) |
| Sleep deprivation mouse model | 16S rRNA gene V3-V4 regions sequencing | •Altered gut microbiota: •↓A. muciniphila, Lactobacillus murinus •↑ Bacteroides massiliensis |
(Park et al., 2020) | |
| CRS mouse model | A. muciniphila (ATCC® BAA-835™) 1.0×108 CFU/200 µl, 3 weeks | •↓CRS−induced depressive−like behavior •↑Corticosterone; Dopamine and BDNF •Regulates gut microbiota at the phylum and genus levels •Regulate gut microbiota function •↑β-alanyl-3-methyl-l-histidine and edaravone |
(Ding et al., 2021) | |
| Antibiotic-treated mouse model |
A. muciniphila (1.5 × 109 CFU/200 µl) Amuc-1100 (100μg/200µl) 3 weeks |
•Alleviated anxiety and depression-like behaviors •Affected the gut microbiota composition •Normalized BDNF/TrkB-related genes in different brain regions •↑5-HT in serum and hippocampus •Affected the HPA axis |
(Sun et al., 2023) | |
| Murine alcohol-LPS (mALPS) mouse model | A. muciniphila 1.5×108 CFU/200 µl, pretreatment 2 weeks | •Ameliorated depression-like behaviors •↑occludin, BDNF and 5-HT •↓LPS, TNF-α, IL-1β and IL-6 |
(Guo et al., 2022) | |
| AD | 25 Egypt AD patients 25 healthy controls |
16S rRNA gene V3-V4 regions sequencing | •↑Akkermansia, Enterobacteria, Bacteroidetes, Bacillus cereus, Prevotella, Clostridium cluster IV •↓Bifidobacterium, Firmicutes, Actinobacteria spp. •Lactic acid bacteria and Prevotella were negatively correlated with cognitive impairment |
(Khedr et al., 2022) |
| 13 Chinese mild AD patients 13 healthy controls |
16S rRNA gene V3-V4 regions sequencing | •β-diversity different •↑Akkermansia, Bifidobacteria •Bifidobacterium, Akkermansia, Coprococcus, Anaerostipes, Sutterella, Coprobacillus as potential markers |
(Wang Y. et al., 2022) | |
| 100 Chinese AD patients 71 healthy controls |
16S rRNA gene V3-V4 regions sequencing | •↓Bacterial diversity •↑Akkermansia, Bififidobacterium •↓Faecalibacterium, Roseburia, Clostridium sensu stricto, Gemmiger, Dialister, Romboutsia, Coprococcus, Butyricicoccus •Faecalibacterium was positively correlated with MMSE, WAIS, and Barthel scores |
(Ling et al., 2020b) | |
| APPswe/PS1de9 (APP/PS1) mouse model | A. muciniphila (5 × 109 CFU/200 µl) 6 months | •Improve glucose tolerance •Improve intestinal mucosal barrier damage •Ameliorate memory impairment and maintain attention. •↓Aβ plaque deposition and Aβ levels |
(Ou et al., 2020) | |
| Conventionally-raised transgenic APPPS1 mouse model | 16S rRNA gene V3-V4 regions sequencing | •↓A. muciniphila, Allobaculum
•↑Rikenellaceae •A. muciniphila is related to Aβ |
(Harach et al., 2017) | |
| PD | 38 PD patients 34 healthy controls |
16S rRNA gene V4 regions sequencing | •Different microbiota diversity and composition between sigmoid mucosal biopsies and fecal samples •↑Blautia, Coprococcus, and Roseburia in PD fecal microbiota •↓Faecalibacterium in mucosal microbiota •↑Ralstonia in mucosal microbiota |
(Keshavarzian et al., 2015) |
| 197 PD patients 103 healthy controls |
16S rRNA gene V4 regions sequencing | •↑Bifidobacterium, Collinsella, Bilophila, and Akkermansia in PD •↓Roseburia, unclassified Lachnospiraceae genus, Faecalibacterium •↓carbohydrate fermentation and butyrate synthesis capacity •↑proteolytic fermentation and production of deleterious amino acid metabolites |
(Cirstea et al., 2020) | |
| 31 Early-stage L-DOPA-naïve PD patients 28 healthy controls |
Shotgun metagenomic sequencing | •↑A. muciniphila, Alistipes shahii and unclassified Firmicutes •↓Prevotella copri, Eubacterium biforme, and Clostridium saccharolyticum •Altered β-glucuronate and tryptophan metabolism |
(Bedarf et al., 2017) | |
| 147 typical PD patients 162 controls |
16S rRNA gene V3-V4 regions sequencing | •↑Species richness in PD •↓Pielou index in female PD patients •Bray-Curtis dissimilarities different •Genus level: ↑Akkermansia, Christensenella, Anaerotruncus, Lactobacillus, Streptococcus, Bilophila, and Acidaminococcus; ↓Turicibacter •Species level: ↑A. muciniphila, Christensenella minuta, Anaerotruncus colihominis, Ruminococcus bromii, Ruminococcus torques, and Roseburia intestinalis; ↓Turicibacter sanguinis •Lactobacillus positively correlated with the disease duration |
(Baldini et al., 2020) | |
| 27 hospitalized PD patients 44 healthy subjects |
16S rRNA gene V3-V4 regions sequencing | •Different α- and β-diversity •↑A. muciniphila, Eubacterium biforme, and Parabacteroides merdae •↓Faecalibacterium prausnitzii, Ruminococcus albus, and Blautia faecis |
(Zapała et al., 2021) | |
| Rotenone-induced PD mouse model | unpredictable restraint stress for 12 weeks, rotenone (10 mg/kg/day) orally in last 6 weeks |
•Intestinal hyper-permeability •↓ZO-1, Occludin, Claudin1 •↑N-tyrosine •↑inflammation in glial cells •Endotoxemia •↓resting microglia;↑ dystrophic/phagocytic microglia •↑A. muciniphila; ↓Coriobacteriaceae •A. muciniphila were positively correlated with serum LPS |
(Dodiya et al., 2020) | |
| MPTP-induced PD mouse model | MPTP (30 mg/kg) 5days +KRG (100 mg/kg) 12 days | •↓dopaminergic neuronal death •↓activation of microglia and astrocytes •↓accumulation of α-synuclein in the SN •Inflammation-related: ↓A. muciniphila, Ruminococcus albus •Anti-inflammatory related: ↑Eubacterium, Flavonifractor, Mucispirillum |
(Jeon et al., 2021) | |
| MS | 40 healthy controls 199 RRMS patients 44 progressive patients EAE mouse model with Akkermansia strains |
16S rRNA gene V4 region sequencing | •↑Shannon diversity, and richness in MS •Altered β-diversity in MS •Progressive MS: ↑Enterobacteriaceae, Ruminococcaceae FJ366134 and Clostridaceae g24 FCEY; ↓Dorea longicatena, Anaerococcus vaginalis, and Blautia faecis •RRMS and Progressive MS: ↑Akkermansia, Clostridium bolteae;↓ Dorea formicigenerans, unclassified Blautia •Akkermansia was negatively correlated with EDSS and MRI burden of MS •Akkermansia strain BWH-H3 ameliorated EAE via reducing RORγt+ and IL-17-producing γδ T cells |
(Cox et al., 2021) |
| 62 RRMS, 15SPMS, 21 atypical MS 20 NMOSD 55 healthy controls |
16S rRNA gene V1-V2 regions and whole metagenomic sequencing | •No changed α-diversity; altered β-diversity among groups •Compared with HC: •↑Bifidobacterium and ↓Megamonas in RRMS; ↑Streptococcus in RRMS and SPMS; ↓Roseburia in SPMS; ↑Alistipes in NMOSD •↑A. muciniphila, Clostridium leptum, Streptococcus parasanguinis, Streptococcus salivarius/thermophilus in RRMS; ↓Eubacterium rectale, Ruminococcus sp. 5_1_39BFAA, and Megamonas funiformis in RRMS •↓fecal acetate, propionate, and butyrate in RRMS |
(Takewaki et al., 2020) | |
| 71 untreated MS patients 71 healthy controls |
16S rRNA gene V4 region sequencing | •No major shifts in microbial community structure •↑A. muciniphila, and Acinetobacter calcoaceticus; ↓Parabacteroides distasoni •A. muciniphila stimulate TH1 differentiation, build proinflammatory environment. |
(Cekanaviciute et al., 2017) | |
| 34 monozygotic twin pairs discordant for MS | 16S rRNA gene V3-V5 regions sequencing and metagenomic sequencing | •No overt differences in alpha or beta diversity •↑A. muciniphila in untreated MS twin siblings |
(Berer et al., 2017) | |
| EAE mouse model | THC+CBD | •↓inflammatory cytokines: IL-17 and IFN-γ •↑anti-inflammatory cytokines: IL-10 and TGF-β •↓A. muciniphila •↓LPS biosynthesis •↑butyric, isovaleric, and valeric acids |
(Al-Ghezi et al., 2019) | |
| Stroke | 16 healthy volunteers; 10 LI patients; 10 AI patients; 10 PI patients |
16S rRNA gene V3 region sequencing | •Altered bacterial diversity in stoke patients •↑Cyanobacteria and Fusobacteria in LI patients •↑Actinobacteria in AI patients •↑Verrucomicrobia, Synergistetes, and Proteobacteria in PI patients •Akkermansia is the predominant genera in PI patients •Pseudomonas, Sphingomonadaceae, and Akkermansia as markers for PI patients |
(Xiang et al., 2020) |
| 30 CI patients; 30 healthy controls |
16S rRNA gene V1-V2 regions sequencing | •Unaltered bacterial diversity in CI patients •↑Odoribacter; Akkermansia; Ruminococcaceae; Victivallis in CI |
(Li et al., 2019) | |
| 8 cerebral infarction patients; 2 ischemia patients; 10 healthy volunteers |
16S rRNA gene V4 region sequencing | •↑Escherichia, Megamonas, Dialister, Bifidobacterium and Ruminococcus in patients •↓Bacteroides, Parabacteroides, Akkermansia, Prevotella and Faecalibacterium in cerebral infarction patients than controls •Escherichia, Dialister and Bifidobacterium in ischemia patients than controls |
(Ji et al., 2017) | |
| 232 acute ischemic stroke patients: 88 PSD 144 non-PSD |
16S rRNA gene V3-V4 regions sequencing | •↑Streptococcus, Akkermansia, and Barnesiella in PSD patients •↓Escherichia-Shigella, Butyricicoccus, and Holdemanella in PSD patient •Akkermansia, Barnesiella, and Pyramidobacter were positively correlated with HAMD-17 score |
(Yao et al., 2023) | |
| Focal cerebral ischemia mouse model | 16S rRNA gene V3-V4 regions sequencing | •↑
Akkermansia, Parabacteroides, Anaerotruncus, Alistipes, Bacteroides in post-stroke mice •↑ A. muciniphila, Parabacteroides goldsteinii, Anaerotruncus colihominis, Alistipes shahii and Roseburia intestinalis in post-stroke mice •Akkermansia was positively correlated with Ruminococcus, Alistipes, Bacteroides and Parabacteroides, but negatively correlated with Staphylococcus and Streptococcus |
(Stanley et al., 2018) | |
| ASD | 23 ASD children; 22 SIB children; 9 controls |
Quantitative real-time PCR | •↓A. muciniphila, Bifidobacterium spp. | (Wang et al., 2011) |
| 48 ASD children; 48 healthy children |
16S rRNA gene V3-V4 regions sequencing | •↑Bacteroidetes/Firmicutes in ASD •↓A. muciniphila, Dialister invisus, Escherichia coli, Bacteroides fragilis, Haemophilus parainflfluenzae, Flavonifractor plautii in ASD •↑Bacteroides coprocola, Bacteroides vulgatus, Eubacterium eligens, Prevotella copri, Roseburia faecis in ASD •metabolic disruptions in ASD |
(Zou et al., 2020) | |
| 20 neurotypical children 20 autistic children |
16S rRNA gene V2-V3 regions sequencing | •Autism children VS neurotypical children: ( ↑Akkermansia, Ruminococcus ( ↓Prevotella, Coprococcus, Blautia, Collinsella |
(Kang et al., 2013) | |
| BTBRT+tf/j (BTBR) mouse model | ketogenic diet for 10-14 days | •triggers gut microbiota remodeling •↑A. muciniphila in the cecum and feces of BTBR animals |
(Newell et al., 2016) | |
| Fmr1 KO mouse model | FMT for the latter 4 weeks | •FMT attenuates cognitive deficits in Fmr1 KO mice •FMT ameliorates social novelty preference •↓A. muciniphila in Fmr1 KO mice •A. muciniphila reduces TNF-α in the cortex and hippocampus •FMT normalized the increased expression level of Iba1 |
(Goo et al., 2020) | |
| VPA induced mouse model | A. muciniphila (1 × 109 CFU/ml) 30μl for 14 days | •A. muciniphila alleviates the social deficit in the VPA-induced mouse model •A. muciniphila enhanced activation of VTA dopaminergic neurons during social interaction. •Early-life A. muciniphila supplementation induced a wide range of metabolic alterations |
(Liu X. et al., 2022) |
5-HT, 5-hydroxytryptamine; AD, Alzheimer’s disease; AI, non-lacunar acute ischemic infarction; ASD, autism spectrum disorder; BDNF, brain-derived neurotrophic factor; CBD, cannabidiol; CFU, colony forming unit; CI, cerebral ischemic stroke; CRS, Chronic restraint stress; EAE, Experimental autoimmune encephalomyelitis; EDSS, expanded disability status score; FMT, fecal microbiota transplantation; HAMD-17, 17-Hamilton Depression Rating Scale; HC, healthy controls; IFN, interferon; IL, interleukin; IS, ischemia; KO, knock out; KRG, Korean red ginseng; LI, lacunar infarction; LPS, lipopolysaccharide; MMSE, Mini-mental State Examination; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MRI, magnetic resonance imaging; MS, multiple sclerosis; NMOSD, neuromyelitis optica spectrum disorder; PD, Parkinson’s disease; PI, post-ischemic stroke; PSD, post-stroke depression; RRMS, Relapsing remitting multiple sclerosis; SIB, siblings; SN, Substantia Nigra; SPMS, secondary progressive multiple sclerosis; TGF, transforming growth factor; THC, delta-9-tetrahydrocannabinol; TNF, tumor necrosis factor; VPA, valproic acid; VTA, ventral tegmental area; WAIS, Wechsler Adult Intelligent Scale.