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. 2019 Apr 21;12(6):1109–1125. doi: 10.1111/1751-7915.13410

Table 3.

Causal relationship between A. muciniphila and disease

Subject Study type Study group Bacterial intervention Bacterial status Sample type Sample detection Treatment outcome
Routy et al. (2018) SPF mice Interventional

  1. αPD‐1: n = 5

  2. αPD‐1 + Nacl: n = 5

  3. αPD‐1 + Akkermansia: n = 5

  4. αPD‐1 + E. hirae: n = 5

  5. αPD‐1 + Akkermansia & E. hirae: n = 5

  6. αPD‐1 + Alistipes ind: n = 5

 Mice exhibiting non‐response FMT‐induced dysbiosis were compensated with A. muciniphila alone or combined with E. hirae or control bacteria during PD‐1 mAb‐based therapy Viable Faeces Metagenomic analysis FMT from cancer patients who did not respond to ICIs into germ‐free or antibiotic‐treated mice failed to ameliorate the antitumour effects of PD‐1 blockade. Oral supplementation with A. muciniphila after FMT with non‐responder faeces restored the efficacy of PD‐1 blockade
Chelakkot et al. (2018) Male 6–8 week C57BL/6 mice Interventional

  1. ND: n = 5–7

  2. HFD: n = 5–7

  3. ND with AmEVs: n = 5–7

  4. HFD with AmEVs: n = 5–7

 Orally administered with 10 μg AmEVs once every two days for two weeks Viable Faeces, colon tissue, rat tail vein blood 16S rRNA sequencing, immunohistochemistry, immunoblotting A. muciniphila extracellular vesicles may improve metabolic function by altering intestinal permeability and barrier integrity in high‐fat diet mice
Plovier et al. (2017) 10‐ to 11‐week‐old male C57BL/6J mice; Human subjects with excess body weight Interventional Mice:

  1. ND

  2. HFD

  3. HFD live Akk mucin

  4. HFD live Akk synthetic

  5. HFD pasteurized AKK

  6. HFD Amuc_1100×


Human:

  1. Placebo

  2. Akk Synthetic – 1010

  3. Akk Synthetic – 109

  4. Akk Pasteurized – 1010

Human subjects were assigned to receive either a daily dose of placebo (an equivalent volume of sterile PBS containing glycerol), 1010 CFU live A. muciniphila (Akk S – 1010), 109 CFU live A. muciniphila (Akk S – 109), or 1010 CFU pasteurized A. muciniphila (Akk P – 1010) for 3 months Live and pasteurized Intestinal tissue, blood Real‐time qPCR A. muciniphila retains its efficacy when grown on a synthetic medium. Pasteurization of A. muciniphila enhanced its capacity to reduce fat mass development, insulin resistance and dyslipidaemia in mice. Administration of live or pasteurized A. muciniphila grown on the synthetic medium is safe in humans
Hanninen et al. (2017) Non‐obese diabetic mice Interventional

  1. Microbiota transplantation group

  2. A. muciniphila group

  3. Control group

 (i) 330 μl bacterial suspension from mice with low diabetes incidence rate, twice daily for three consecutive days (ii) Orally administered 2 × 108 cfu A. muciniphila, three times a week for 7 weeks
(iii) Orally administered 2 × 106 cfu A. muciniphila, three times a week for 7 weeks 		Viable Faeces, caecal and colon contents 16S rRNA sequencing Transplanting the gut microbiota of mice with low diabetes incidence to mice with high diabetes incidence did not reduce the morbidity of diabetes; but transplanting the single strain A. muciniphila to mice with high incidence of diabetes can reduce the morbidity of diabetes
Li et al. (2016) Eight‐week‐old male Apoe−/− mice Interventional

  1. NCD: n = 8–10

  2. WD: n = 8–10

  3. WD+Akk: n = 8–10

  4. WD+hk‐Akk: n = 8–10

  5. WD+PBS: n = 8–10

 The Western diet‐fed mice were further separated into three groups: a group receiving daily oral gavage with live A muciniphila (WD+Akk), a group receiving daily oral gavage with heat‐killed A muciniphila (WD+hk‐Akk), and a third gavaged with PBS as vehicle control (WD+PBS) Live Aorta and ileum Real‐time qPCR Oral gavage with A muciniphila protected against western diet‐induced atherosclerotic lesion formation in Apoe−/− Mice
Shin et al. (2014) C57BL/6 mice Interventional

  1. NCD‐fed control mice: n = 6

  2. HFD‐fed control mice: n = 6

  3. HFD‐fed metformin‐treated mice: n = 6

  4. HFD‐fed Akk‐administered mice: n = 6

 The bacteria were harvested at the late exponential growth phase, suspended in thioglycolate–phosphate‐buffered saline (PBS) (4.0 × 108 cfu) and orally administered to HFD‐fed mice (HFD‐Akk; n = 6) Viable Faeces 16S rRNA gene sequences with 454 pyrosequencing Oral administration of Akkermansia muciniphila to HFD‐fed mice without metformin significantly enhanced glucose tolerance and attenuated adipose tissue inflammation by inducing Foxp3 regulatory T cells (Tregs) in the visceral adipose tissue
Kang et al. (2013) Specific pathogen free C57BL/6 mice Interventional

  1. Water: n = 5

  2. 2% DSS: n = 5

  3. 2% DSS + A. muciniphila: n = 5

  4. 2% DSS + AmEV: n = 5

 2% DSS was administered to female C57BL/6 mice for 5 days, and then, mice were treated with 2% DSS and A. muciniphila (5 × 108 CFU per mouse), and treated with 2% DSS and A. muciniphila‐derived EV (AmEV, 100 mg/mouse). Viable Small intestinal fluids and stools Metagenome sequencing A. muciniphila‐derived extracellular vesicles have protective effects in the development of DSS‐induced colitis
Everard et al. (2013) 10‐week C57BL/6 mice Interventional

  1. CT control diet group: n = 4

  2. HF high‐fat diet group (60% fat): n = 6

  3. HF‐AKK group (+ A. muciniphila live bacteria): n = 5

  4. HF‐K‐AKK group (+ A. muciniphila heat‐killed bacteria): n = 5

 Intragastric administration of A. muciniphila (live bacteria, heat‐killed bacteria, 2 × 108 cfu 0.2 ml−1) Live and heat‐killed Caecal contents, collected every day 16S rRNA sequencing, qPCR A. muciniphila abundance was decreased in mice with diabetes and obesity caused by high‐fat diet, and the metabolic function of mice could be improved by intragastric administration of live A. muciniphila

AmEVs, A. muciniphila extracellular vesicles; DSS, dextran sulphate sodium; FMT, faecal microbiota transplantation; HFD, high‐fat diet; ICIs, immune checkpoint inhibitors; NCD, normal chow diet; ND, normal diet; PBS, phosphate‐buffered saline; SPF, specific pathogen‐free; WD, Western diet.