Role of Akkermansia muciniphila in the development of nonalcoholic fatty liver disease: current knowledge and perspectives

doi:10.1007/s11684-022-0960-z

Frontiers of Medicine

2022, Vol. 16

Issue (5): 667-685 https://doi.org/10.1007/s11684-022-0960-z

本期目录

Role of Akkermansia muciniphila in the development of nonalcoholic fatty liver disease: current knowledge and perspectives

Yuqiu Han¹, Lanjuan Li^1,^2,³, Baohong Wang^1,^2,³(

)

¹. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
². Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou 310003, China
³. Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China

全文: PDF(3098 KB) HTML

Abstract：

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome and a common cause of liver cirrhosis and cancer. Akkermansia muciniphila (A. muciniphila) is a next-generation probiotic that has been reported to improve metabolic disorders. Emerging evidence indicates the therapeutic potential of A. muciniphila for NAFLD, especially in the inflammatory stage, nonalcoholic steatohepatitis. Here, the current knowledge on the role of A. muciniphila in the progression of NAFLD was summarized. A. muciniphila abundancy is decreased in animals and humans with NAFLD. The recovery of A. muciniphila presented benefits in preventing hepatic fat accumulation and inflammation in NAFLD. The details of how microbes regulate hepatic immunity and lipid accumulation in NAFLD were further discussed. The modulation mechanisms by which A. muciniphila acts to improve hepatic inflammation are mainly attributed to the alleviation of inflammatory cytokines and LPS signals and the downregulation of microbiota-related innate immune cells (such as macrophages). This review provides insights into the roles of A. muciniphila in NAFLD, thereby providing a blueprint to facilitate clinical therapeutic applications.

Key words： Akkermansia muciniphila NAFLD NASH steatosis inflammation

收稿日期: 2022-05-25 出版日期: 2022-11-18

Corresponding Author(s): Baohong Wang

引用本文:

. [J]. Frontiers of Medicine, 2022, 16(5): 667-685.
Yuqiu Han, Lanjuan Li, Baohong Wang. Role of Akkermansia muciniphila in the development of nonalcoholic fatty liver disease: current knowledge and perspectives. Front. Med., 2022, 16(5): 667-685.

链接本文:

https://academic.hep.com.cn/fmd/CN/10.1007/s11684-022-0960-z
https://academic.hep.com.cn/fmd/CN/Y2022/V16/I5/667

Fig.1

Reference	Subjects/diets	Severity of NAFLD	Study group	Sample type (detection method)	Changes in Akkermansia muciniphila or Akkermansia
Animals
Kim et al. (2020) [21]	Male C57BL/6N mice, HFD, 10 weeks	NAFL (H&E staining; serum ALT and AST↑)	1. Normal diet (ND + PBS, n = 5); 2. HFD + PBS (n = 5); 3. ND + A. muciniphila (n = 5); 4. HFD + A. muciniphila (n = 5)	Cecal contents (16S rRNA gene sequencing)	↓
Shi et al. (2021) [44]	Female C57BL/6 mice, saccharin or sucralose, 11 weeks	NASH (histopathological changes)	1. Control (n = 10); 2. neohesperidin dihydrochalcone (NHDC, n = 10); 3. saccharin (n = 10); 4. sucralose (n = 10)	Cecal contents (16S rRNA gene sequencing, metagenomic sequencing)	↓
Natividad et al. (2018) [48]	Male C57BL/6J mice, HFD, 9 weeks	NAFL (H&E staining; serum ALT and AST↑)	1. Control diet (CD, n = 10); 2. HFD (n = 10); 3. CD + B. wadsworthia (n = 10); 4. HFD + B. wadsworthia (n = 10)	Feces (16S rRNA gene sequencing)	↓
Hussain et al. (2016) [49]	Male C57BL/6 mice, HFD, 12 weeks	NAFL (Oil Red O staining)	1. Normal chow diet (NCR, n = 7); 2. HFD (n = 7); 3. HFD + orilistat (ORL, n = 7); 4. HFD + daesiho-tang (DSHT, n = 7)	Feces (qPCR)	↓ (tendency)
Lee et al. (2018) [50]	Male C57BL/6 mice, HFD, 12 weeks	NAFL (H&E staining)	1. ND (n = 5); 2. HFD (n = 5); 3. HFD-fed mice treated with a mixture of two L. plantarum strains (DSR, n = 5)	Cecal contents (16S rRNA gene sequencing, qPCR)	↓
Wang et al. (2019) [51]	Male C57BL/6 mice, HFD, 13 weeks	NAFL (H&E and Oil Red O staining; serum ALT ↑)	1. Normal control (NC, n = 6); 2. HFD (n = 6); 3. NC + puerarin (NC + PUE) (n = 6); 4. HFD + PUE (n = 6)	Feces (16S rRNA gene sequencing)	↓
Schneeberger et al. (2015) [52]	Male C57BL/6 mice, HFD, 16 weeks	Unknown	1. CT diet (CT, n = 6); 2. HFD (n = 6)	Cecal contents (qPCR)	Negative correlation with age and HFD feeding
Ye et al. (2018) [53]	Male C57BL/6 mice, methionine-choline-deficient (MCD) diet, 4 weeks	NASH (histopathological changes)	1. Control (n = 6); 2. MCD (n = 6)	Feces (16S rRNA gene sequencing)	↓
Moreira et al. (2018) [72]	Male C57BL/6 mice, HFD, 10 weeks	NASH (histopathological changes)	1. Control group (C); 2. C + liraglutide (C + L); 3. HFD; 4. HFD + liraglutide (HFD + L)	Feces (16S rRNA gene sequencing)	Liraglutide increased its abundance in HFD mice
Du et al. (2021) [73]	Kunming female mice, HFD, 23 weeks	NAFL (Oil Red O staining; serum ALT and AST ↑)	1. Normal chow (Chow, n = 6); 2. HFD (n = 6); 3. chow + betaine (Chow + B) (n = 6); 4. HFD + B (n = 6)	Feces (16S rRNA gene sequencing)	↓
Zhang et al. (2022) [74]	Male C57BL/6 mice, HFD, 12 weeks	NASH (histopathological changes; serum ALT/AST ↑)	1. Control group (Con, n = 5); 2. HFD (n = 5); 3. HFD + purified MDG (MDG-1. n = 5); 4. HFD + coarse MDG (MDG-C, n = 5); 5. HFD + inulin (Inu, n = 5); 6. HFD + antibiotics (Anti, n = 5)	Feces (metagenomic sequencing)	↓, negative correlation with most NAFLD parameters
Wang et al. (2021) [75]	Male C57BL/6J mice, HFD, 30 weeks	NASH (hepatic steatosis; hepatic TNFα, MCP-1, IL-6 and ROS ↑; serum ALT, AST, ALP, and γ-GT ↑; hepatic fibrosis)	1. NCD-fed mice (Control); 2. HFD-fed mice (Model); 3. HFD + metformin (Metf); 4. HFD + 100 mg/kg/day of PYOs (PYOs-L); 5. HFD + 300 mg/kg/d of PYOs (PYOs-H)	Cecal contents (16S rRNA gene sequencing)	Negative correlation with the development of NAFLD
Han et al. (2021) [76]	Male C57BL/6 mice, high fat/high sucrose (HFHS), 16 weeks	NAFL (H&E and Oil Red O staining; serum ALT and AST ↑)	1. Control group (Con, n = 5); 2. HFHS (n = 5); 3. HFHS + low-dose SMF (SMF-L, n = 5); 4. HFHS + high-dose SMF (SMF-H, n = 5)	Cecal contents (16S rRNA gene sequencing)	↑ (tendency)
Bao et al. (2021) [79]	Male C57BL/6J mice, HFD, 14 weeks	NASH (NAS scores ↑; hepatic IL-1β, IL-18, IL-6 and TNF-α ↑; hepatic macrophages ↑)	1. ND (n = 5); 2. HFD (n = 5); 3. ND + inulin (ND-INU, n = 5); 4. HFD + inulin (HFD-INU, n = 5)	Feces (16S rRNA gene sequencing)	↓
Cui et al. (2020) [80]	Male Sprague–Dawley rats, HFD, 12 weeks	NASH (histopathological changes; serum ALT/AST ↑)	1. Control (n = 10); 2. HFD (model, n = 10); 3. HFD + metformin (positive control, n = 10); 4. HFD + Da-Chai-Hu (DCH, n = 10)	Feces (16S rRNA gene sequencing)	↓
Nakano et al. (2020) [81]	Male C57BL/6J mice, Western diet, 12 weeks	NAFL (Oil Red O staining; serum ALT ↑)	1. ND (n = 4); 2. ND + 2% BA group (NDBA, n = 2); 3. Western diet (WD, n = 4); 4. WD + 2% BA (WDBA, n = 4)	Feces (16S rRNA gene sequencing)	AST and ALT were positively correlated with family Verrucomicrobiaceae
Mu et al. (2020) [82]	Male C57BL/6J mice, HFD/F (high fat + 10% fructose solution), 8 weeks	NAFL (H&E staining; serum ALT, AST, AKP and hepatic ROS ↑)	1. Normal group (Normal); 2. HFD (Model); 3. L-carnitine; 4. HFD + low-concentration L. fermentum CQPC06 (LCQPC06); 5. HFD + high-concentration L. fermentum CQPC06 (HCQPC06); 6. HFD + Lactobacillus delbrueckii subsp. Bulgaricus (LDSB)	Feces (16S rRNA gene sequencing)	↓
Xie et al. (2020) [83]	Male C57BL/6J mice, Western diet, 12 weeks	NAFL (H&E staining; serum ALT and AST ↑)	1. ND (n = 4); 2. ND + 1% vine tea polyphenols (ND + 1% VTP, n = 4); 3. WD (n = 4); 4. WD + 0.5% VTP (n = 4); 5. WD + 1% VTP (n = 4); 6. WD + 2% VTP (n = 4)	Feces (16S rRNA gene sequencing)	↓
Nishiyama et al. (2020) [84]	Male ob/ob mice, standard diet, 4 weeks	NASH (histopathological changes; serum ALT/AST ↑)	1. C57BL/6J mice fed standard diet (WILD, n = 6); 2. ob/ob mice fed with standard diet (CONT, n = 6); 3. ob/ob mice fed with standard diet containing 5% bofutsushosan (BTS) (n = 6)	Feces (16S rRNA gene sequencing, qPCR)	Negative correlation with suppression of body weight gain
Li et al. (2020) [85]	Male C57BL/6J mice, HFD, 18 weeks	NASH (histopathological changes; serum ALT and AST ↑)	1. Normal chow diet (NCD, n = 8); 2. HFD (n = 8); 3. HFD + fed with 0.5% carboxymethylcellulose sodium (CMC-Na) (n = 8); 4. HFD + Sil (100 mg/kg, HFD + Sil group 1, n = 8); 5. HFD + Sil (300 mg/kg, HFD + Sil group 2, n = 8)	Cecal contents (16S rRNA gene sequencing)	↓
Régnier et al. (2020) [87]	Male C57BL/6J mice, high-fat and high-sucrose diet (HFHS), 8 weeks	NAFL (hepatic triglycerides ↑)	1. Control diet (CTRL, n = 10); 2. HFHS (n = 10); 3. HFHS + 0.3% (g/g) of rhubarb (RHUB, n = 10)	Feces (16S rRNA gene sequencing, qPCR)	Rhubarb promotes its growth in HFHS-fed mice
Juárez-Fernández et al. (2022) [88]	Wistar rats, HFD, 9 weeks	NAL (histopathological changes; serum ALT and AST ↑)	1. Control group (C) (n = 7); 2. HFD (n = 7); 3. C + quercetin (n = 7); 4. C + A. muciniphila; 5. HFD + quercetin (n = 7); 6. HFD + A. muciniphila (n = 8); 7. C + quercetin + A. muciniphila (n = 8); 8. HFD + quercetin + A. muciniphila (n = 8)	Feces (16S rRNA gene sequencing)	The colonization with Akkermansia muciniphila was associated with less body fat
Human
Hoyles et al. (2018) [59]	Morbidly obese women	NAFL (diagnosed by histology)	1. No liver steatosis (n = 10); 2. liver steatosis 1 (n = 22); 3. liver steatosis 2 (n = 14); 4. liver steatosis 3 (n = 10)	Feces (metagenomic sequencing)	Increased trend in women with obesity. Verrucomicrobia and Akkermansia were significantly correlated with liver steatosis
Nistal et al. (2019) [60]	Adults with obesity	NAFLD (diagnosed by clinical, analytical and ultrasonographic data)	1. Twenty healthy adults (n = 20); 2. obese patients with NAFLD (n = 36); 3. obese patients without NAFLD (n = 17)	Feces (16S rRNA gene sequencing)	Reduced trend in patients with obesity with NAFLD
Tsai et al. (2021) [61]	Patients with T2DM	NAFLD (diagnosed by ultrasonographic data)	1. Patients with T2DM with no or mild NAFLD (n = 80); 2. patients with T2DM with moderate or severe NAFLD (n = 83)	Feces (qPCR)	Decreased trend in patients with T2DM with moderate/severe NAFLD
Lee et al. (2021) [62]	Patients with NAFLD	NAFLD (diagnosed by abdominal ultrasound or computed tomography with elevated liver enzyme)	1. Healthy controls (n = 37); 2. NAFLD (n = 57)	Feces (16S rRNA gene sequencing)	↓
Özkul et al. (2017) [63]	Patients with NASH	NASH (diagnosed by histology)	1. Healthy controls (n = 38); 2. NAFLD (n = 46)	Feces (qPCR)	↓
Chierico et al. (2017) [64]	Children and adolescents	NAFL and NASH (diagnosed by liver ultrasound and percutaneous liver biopsy)	1. NAFL (n = 27); 2. NASH (n = 26); 3. obesity (n = 8) 4. case-controls (CTRLs, n = 54)	Feces (16S rRNA gene sequencing)	Decreased trend in pediatric patients with NAFLD
Pan et al. (2021) [65]	Children with obesity	NAFL (diagnosed by ultrasonography) and NASH (unknown diagnostic criterion)	1. NAFL (n = 25); 2. NASH (n = 25); 3. obese without NAFLD (n = 25)	Feces (16S rRNA gene sequencing)	↓
Schwimmer et al. (2019) [66]	Children who are overweight/obese	NAFLD (diagnosed by liver biopsy)	1. Overweight/obese children without NAFLD (n = 37); 2. children with NAFLD (n = 86, including 38 NAFL, 37 borderline NASH, and 11 NASH)	Feces (16S rRNA gene sequencing, metagenomic sequencing)	Decreased in children with NASH or moderate/severe fibrosis
Ponziani et al. (2019) [67]	Patients with NAFLD	NAFLD with cirrhosis (diagnosed by histological and/or clinical findings) and HCC (diagnosed by histology)	1. Patients with NAFLD-related cirrhosis and HCC (n = 21); 2. NAFLD-related cirrhosis without HCC (n = 20); 3. healthy controls (n = 20)	Feces (16S rRNA gene sequencing)	Decreased in NAFLD patients with cirrhosis
Dao et al. (2016) [58]	Adults who are overweight and obese	Unknown	1. Lower A. muciniphila abundance in baseline (Akk LO, n = 24); 2. higher A. muciniphila abundance in baseline (Akk HI, n = 25)	Feces (qPCR)	Akk HI group had lower AST and GGT and greatest benefits from dietary intervention
Liu et al. (2017) [68]	Patients with obesity	Obesity with elevation of serum ALT, AST, ALP, and GGT levels	1. Lean controls (n = 79); 2. individuals with obesity (n = 72)	Feces (metagenomic sequencing)	Enriched in lean controls; positive correlation with the concentration of circulating adiponectin
Kordy et al. (2021) [70]	Children and adolescents	NASH (diagnosed by liver biopsy)	1. NASH (n = 20); 2. control subjects (n = 20)	Feces (metagenomic sequencing)	↓

Tab.1

Reference	Diet	Subjects	Diseases	Dosages	Time	Colonization (detection method)	Study group	Efficiency of treatment
Animals
Kim et al. (2020) [21]	HFD	Male C57BL/6N mice	NAFL (H&E staining; serum ALT and AST levels ↑)	Live, 10⁸–10⁹ CFU/mL	10 weeks	Obviously increased abundance (16S rRNA gene sequencing)	1. Normal diet (ND + PBS, n = 5); 2. HFD + PBS (n = 5); 3. ND + A. muciniphila (n = 5); 4. HFD + A. muciniphila (n = 5)	Serum TG and ALT levels↓; the gene expression of hepatic TG synthesis and inflammatory factor IL-6↓
Rao et al. (2021) [38]	High-fat and high-cholesterol (HFC) diet	Male C57BL/6J mice	NASH (histopathological changes)	Live, 1 × 10⁸ CFU/ mL, 200 μL, every other day	6 weeks	Increased by 20-fold (qPCR)	1. HFC (n = 5–8); 2. HFC + A. muciniphila (n = 5–8)	Hepatic steatosis/ inflammatory (indicated by HE staining) ↓, serum ALT/AST/ALP↓, and hepatic genes expression related to steatosis and inflammation↓
Higarza et al. (2021) [92]	High-fat, high cholesterol diet (HFHC)	Male Sprague–Dawley rats	NASH-induced cognitive damage	Live, 10⁹ CFU, 100 μL, daily	4 weeks	No differences (16S rRNA gene sequencing and qPCR)	1. NC group (n = 8); 2. HFHC + PBS (n = 8); 3. HFHC + Lacticaseibacillus rhamnosus GG (HFHC + LGG, n = 8); 4. HFHC + A. muciniphila CIP107961(HFHC + AKK, n = 8)	HFHC-induced cognitive dysfunction (including impaired spatial working memory and novel object recognition) ↓
Human
Depommier et al. (2019) [18]	/	/	Overweight/obese insulin-resistant volunteers	Live (10¹⁰ or 10⁹ CFU per day) or pasteurized A. muciniphila (10¹⁰ CFU per day)	3 months	Unknown	1. Placebo group (n = 11); 2. pasteurized bacteria group (n = 12); 3. live bacteria group (n = 9)	Blood markers for liver dysfunction including γ-glutamyltransferase (GGT) and AST↓
Other liver diseases
Grander et al. (2018) [22]	Lieber-De-Carli diet containing 1–5 vol.%	Female WT mice	Alcoholic liver disease (ALD)	Live, 1.5 × 10⁹ CFU, 200 μL, every other day	2 day or 15 days or 6 days	Obviously increased abundance (qPCR)	1. Pair fed (Ctrl); 2. Pair fed + A. muciniphila (Ctrl + A.muc); 3. ethanol fed (EtOH); 4. ethanol fed + A. muciniphila (EtOH + A.muc)	Acute ethanol-induced hepatic injury and inflammation↓; chronic ethanol-induced hepatic inflammation and steatosis↓
Keshavarz et al. (2021) [23]	HFD (+ CCl₄ injection)	Male C57BL/6 mice	Liver injury (liver fabrosis)	10⁹ CFU/200 μL live or pasteurized A. muciniphila, 50 mg/200 μL Evs, daily	4 weeks	Obviously increased abundance (qPCR)	1. Healthy control animals (ND, n = 5); 2. HFD/CCl₄ + PBS (PBS, n = 5); 3. HFD/CCl₄ + live A. muciniphila (Am) (n = 5); 4. HFD/CCl₄ + pasteurized A. muciniphila (Pam, n = 5); 5. HFD/CCl₄ + EV (EV, n = 5)	Serum liver enzymes↓; hepatic inflammation and fibrosis markers↓
Wu et al. (2017) [25]	Normal chow diets (+ concanavalin A injection)	Male C57BL/6 mice	Liver injury (resembling autoimmune liver diseases and virus hepatitis)	Live, 3 × 10⁹ CFU, 200 μL, daily	14 days	Obviously increased abundance (16S rRNA gene sequencing)	1. A. muciniphila + Con A (Akk, n = 7); 2. PBS + Con A (Control, n = 7); 3. PBS + PBS (Normal, n = 8)	Serum ALT and AST↓; liver histopathological damage↓

Tab.2

Fig.2

Fig.3

Fig.4

1	SK Asrani, H Devarbhavi, J Eaton, PS Kamath. Burden of liver diseases in the world. J Hepatol 2019; 70(1): 151–171 https://doi.org/10.1016/j.jhep.2018.09.014 pmid: 30266282
2	JV Lazarus, HE Mark, QM Anstee, JP Arab, RL Batterham, L Castera, H Cortez-Pinto, J Crespo, K Cusi, MA Dirac, S Francque, J George, H Hagström, TT Huang, MH Ismail, A Kautz, SK Sarin, R Loomba, V Miller, PN Newsome, M Ninburg, P Ocama, V Ratziu, M Rinella, D Romero, M Romero-Gómez, JM Schattenberg, EA Tsochatzis, L Valenti, VW Wong, Y Yilmaz, ZM Younossi, SNAFLD Consensus Consortium Zelber-Sagi;. Advancing the global public health agenda for NAFLD: a consensus statement. Nat Rev Gastroenterol Hepatol 2022; 19(1): 60–78 https://doi.org/10.1038/s41575-021-00523-4 pmid: 34707258
3	SR Sharpton, B Schnabl, R Knight, R Loomba. Current concepts, opportunities, and challenges of gut microbiome-based personalized medicine in nonalcoholic fatty liver disease. Cell Metab 2021; 33(1): 21–32 https://doi.org/10.1016/j.cmet.2020.11.010 pmid: 33296678
4	SL Friedman, BA Neuschwander-Tetri, M Rinella, AJ Sanyal. Mechanisms of NAFLD development and therapeutic strategies. Nat Med 2018; 24(7): 908–922 https://doi.org/10.1038/s41591-018-0104-9 pmid: 29967350
5	J Aron-Wisnewsky, MV Warmbrunn, M Nieuwdorp, K Clément. Nonalcoholic fatty liver disease: modulating gut microbiota to improve severity?. Gastroenterology 2020; 158(7): 1881–1898 https://doi.org/10.1053/j.gastro.2020.01.049 pmid: 32044317
6	AA Kolodziejczyk, D Zheng, O Shibolet, E Elinav. The role of the microbiome in NAFLD and NASH. EMBO Mol Med 2019; 11(2): e9302 https://doi.org/10.15252/emmm.201809302 pmid: 30591521
7	AR Moschen, S Kaser, H Tilg. Non-alcoholic steatohepatitis: a microbiota-driven disease. Trends Endocrinol Metab 2013; 24(11): 537–545 https://doi.org/10.1016/j.tem.2013.05.009 pmid: 23827477
8	C Leung, L Rivera, JB Furness, PW Angus. The role of the gut microbiota in NAFLD. Nat Rev Gastroenterol Hepatol 2016; 13(7): 412–425 https://doi.org/10.1038/nrgastro.2016.85 pmid: 27273168
9	JS Bajaj, A Khoruts. Microbiota changes and intestinal microbiota transplantation in liver diseases and cirrhosis. J Hepatol 2020; 72(5): 1003–1027 https://doi.org/10.1016/j.jhep.2020.01.017 pmid: 32004593
10	T Zhang, Q Li, L Cheng, H Buch, F Zhang. Akkermansia muciniphila is a promising probiotic. Microb Biotechnol 2019; 12(6): 1109–1125 https://doi.org/10.1111/1751-7915.13410 pmid: 31006995
11	PD CaniC DepommierM DerrienA EverardWM de Vos. Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms. Nat Rev Gastroenterol Hepatol 2022; [Epub ahead of print] doi: 10.1038/s41575-022-00631-9
12	Q Zhai, S Feng, N Arjan, W Chen. A next generation probiotic, Akkermansia muciniphila. Crit Rev Food Sci Nutr 2019; 59(19): 3227–3236 https://doi.org/10.1080/10408398.2018.1517725 pmid: 30373382
13	J Yan, L Sheng, H Li. Akkermansia muciniphila: is it the Holy Grail for ameliorating metabolic diseases?. Gut Microbes 2021; 13(1): 1984104 https://doi.org/10.1080/19490976.2021.1984104 pmid: 34674606
14	M Derrien, EE Vaughan, CM Plugge, WM de Vos. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol 2004; 54(5): 1469–1476 https://doi.org/10.1099/ijs.0.02873-0 pmid: 15388697
15	M Derrien, MC Collado, K Ben-Amor, S Salminen, WM de Vos. The mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract. Appl Environ Microbiol 2008; 74(5): 1646–1648 https://doi.org/10.1128/AEM.01226-07 pmid: 18083887
16	Q ZhaoJ YuY HaoH ZhouY Hu C ZhangH ZhengX WangF ZengJ Hu L GuZ Wang F ZhaoC YueP ZhouH ZhangN Huang W WuY Zhou J Li. Akkermansia muciniphila plays critical roles in host health. Crit Rev Microbiol 2022; [Epub ahead of print] doi: 10.1080/1040841X.2022.2037506 pmid: 35603929
17	J Si, H Kang, HJ You, G Ko. Revisiting the role of Akkermansia muciniphila as a therapeutic bacterium. Gut Microbes 2022; 14(1): 2078619 https://doi.org/10.1080/19490976.2022.2078619 pmid: 35613313
18	C Depommier, A Everard, C Druart, H Plovier, M Van Hul, S Vieira-Silva, G Falony, J Raes, D Maiter, NM Delzenne, M de Barsy, A Loumaye, MP Hermans, JP Thissen, WM de Vos, PD Cani. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med 2019; 25(7): 1096–1103 https://doi.org/10.1038/s41591-019-0495-2 pmid: 31263284
19	A Everard, C Belzer, L Geurts, JP Ouwerkerk, C Druart, LB Bindels, Y Guiot, M Derrien, GG Muccioli, NM Delzenne, WM de Vos, PD Cani. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci USA 2013; 110(22): 9066–9071 https://doi.org/10.1073/pnas.1219451110 pmid: 23671105
20	M Bae, CD Cassilly, X Liu, SM Park, BK Tusi, X Chen, J Kwon, P Filipčík, AS Bolze, Z Liu, H Vlamakis, DB Graham, SJ Buhrlage, RJ Xavier, J Clardy. Akkermansia muciniphila phospholipid induces homeostatic immune responses. Nature 2022; 608(7921): 168–173 https://doi.org/10.1038/s41586-022-04985-7 pmid: 35896748
21	S Kim, Y Lee, Y Kim, Y Seo, H Lee, J Ha, J Lee, Y Choi, H Oh, Y Yoon. Akkermansia muciniphila prevents fatty liver disease, decreases serum triglycerides, and maintains gut homeostasis. Appl Environ Microbiol 2020; 86(7): e03004–19 https://doi.org/10.1128/AEM.03004-19 pmid: 31953338
22	C Grander, TE Adolph, V Wieser, P Lowe, L Wrzosek, B Gyongyosi, DV Ward, F Grabherr, RR Gerner, A Pfister, B Enrich, D Ciocan, S Macheiner, L Mayr, M Drach, P Moser, AR Moschen, G Perlemuter, G Szabo, AM Cassard, H Tilg. Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease. Gut 2018; 67(5): 891–901 https://doi.org/10.1136/gutjnl-2016-313432 pmid: 28550049
23	S Keshavarz Azizi Raftar, F Ashrafian, A Yadegar, A Lari, HR Moradi, A Shahriary, M Azimirad, H Alavifard, Z Mohsenifar, M Davari, F Vaziri, A Moshiri, SD Siadat, MR Zali. The protective effects of live and pasteurized Akkermansia muciniphila and its extracellular vesicles against HFD/CCl4-induced liver injury. Microbiol Spectr 2021; 9(2): e0048421 https://doi.org/10.1128/Spectrum.00484-21 pmid: 34549998
24	M Derrien, C Belzer, WM de Vos. Akkermansia muciniphila and its role in regulating host functions. Microb Pathog 2017; 106: 171–181 https://doi.org/10.1016/j.micpath.2016.02.005 pmid: 26875998
25	W Wu, L Lv, D Shi, J Ye, D Fang, F Guo, Y Li, X He, L Li. Protective effect of Akkermansia muciniphila against immune-mediated liver injury in a mouse model. Front Microbiol 2017; 8: 1804 https://doi.org/10.3389/fmicb.2017.01804 pmid: 29033903
26	C Chelakkot, Y Choi, DK Kim, HT Park, J Ghim, Y Kwon, J Jeon, MS Kim, YK Jee, YS Gho, HS Park, YK Kim, SH Ryu. Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions. Exp Mol Med 2018; 50(2): e450 https://doi.org/10.1038/emm.2017.282 pmid: 29472701
27	A Alam, G Leoni, M Quiros, H Wu, C Desai, H Nishio, RM Jones, A Nusrat, AS Neish. The microenvironment of injured murine gut elicits a local pro-restitutive microbiota. Nat Microbiol 2016; 1(2): 15021 https://doi.org/10.1038/nmicrobiol.2015.21 pmid: 27571978
28	S Kim, YC Shin, TY Kim, Y Kim, YS Lee, SH Lee, MN Kim, E O, KS Kim, MN Kweon. Mucin degrader Akkermansia muciniphila accelerates intestinal stem cell-mediated epithelial development. Gut Microbes 2021; 13(1): 1892441 https://doi.org/10.1080/19490976.2021.1892441 pmid: 33678130
29	MM Pérez, LMS Martins, MS Dias, CA Pereira, JA Leite, ECS Gonçalves, Almeida PZ de, Freitas EN de, RC Tostes, SG Ramos, Zoete MR de, B Ryffel, JS Silva, D Carlos. Interleukin-17/interleukin-17 receptor axis elicits intestinal neutrophil migration, restrains gut dysbiosis and lipopolysaccharide translocation in high-fat diet-induced metabolic syndrome model. Immunology 2019; 156(4): 339–355 https://doi.org/10.1111/imm.13028 pmid: 30472727
30	JS Lee, CM Tato, B Joyce-Shaikh, MF Gulen, C Cayatte, Y Chen, WM Blumenschein, M Judo, G Ayanoglu, TK McClanahan, X Li, DJ Cua. Interleukin-23-independent IL-17 production regulates intestinal epithelial permeability. Immunity 2015; 43(4): 727–738 https://doi.org/10.1016/j.immuni.2015.09.003 pmid: 26431948
31	G Tarantino, S Costantini, C Finelli, F Capone, E Guerriero, N La Sala, S Gioia, G Castello. Is serum interleukin-17 associated with early atherosclerosis in obese patients?. J Transl Med 2014; 12(1): 214 https://doi.org/10.1186/s12967-014-0214-1 pmid: 25092442
32	S Qu, L Fan, Y Qi, C Xu, Y Hu, S Chen, W Liu, W Liu, J Si. Akkermansia muciniphila alleviates dextran sulfate sodium (DSS)-induced acute colitis by NLRP3 activation. Microbiol Spectr 2021; 9(2): e0073021 https://doi.org/10.1128/Spectrum.00730-21 pmid: 34612661
33	L Wang, L Tang, Y Feng, S Zhao, M Han, C Zhang, G Yuan, J Zhu, S Cao, Q Wu, L Li, Z Zhang. A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8+ T cells in mice. Gut 2020; 69(11): 1988–1997 https://doi.org/10.1136/gutjnl-2019-320105 pmid: 32169907
34	Y Liu, M Yang, L Tang, F Wang, S Huang, S Liu, Y Lei, S Wang, Z Xie, W Wang, X Zhao, B Tang, S Yang. TLR4 regulates RORγt+ regulatory T-cell responses and susceptibility to colon inflammation through interaction with Akkermansia muciniphila. Microbiome 2022; 10(1): 98 https://doi.org/10.1186/s40168-022-01296-x pmid: 35761415
35	S Lukovac, C Belzer, L Pellis, BJ Keijser, WM de Vos, RC Montijn, G Roeselers. Differential modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids. MBio 2014; 5(4): e01438–14 https://doi.org/10.1128/mBio.01438-14 pmid: 25118238
36	Z Gu, W Pei, Y Shen, L Wang, J Zhu, Y Zhang, S Fan, Q Wu, L Li, Z Zhang. Akkermansia muciniphila and its outer protein Amuc_1100 regulates tryptophan metabolism in colitis. Food Funct 2021; 12(20): 10184–10195 https://doi.org/10.1039/D1FO02172A pmid: 34532729
37	B Stockinger, K Shah, E Wincent. AHR in the intestinal microenvironment: safeguarding barrier function. Nat Rev Gastroenterol Hepatol 2021; 18(8): 559–570 https://doi.org/10.1038/s41575-021-00430-8 pmid: 33742166
38	Y Rao, Z Kuang, C Li, S Guo, Y Xu, D Zhao, Y Hu, B Song, Z Jiang, Z Ge, X Liu, C Li, S Chen, J Ye, Z Huang, Y Lu. Gut Akkermansia muciniphila ameliorates metabolic dysfunction-associated fatty liver disease by regulating the metabolism of L-aspartate via gut-liver axis. Gut Microbes 2021; 13(1): 1927633 https://doi.org/10.1080/19490976.2021.1927633 pmid: 34030573
39	A Albillos, A de Gottardi, M Rescigno. The gut-liver axis in liver disease: pathophysiological basis for therapy. J Hepatol 2020; 72(3): 558–577 https://doi.org/10.1016/j.jhep.2019.10.003 pmid: 31622696
40	DM Chopyk, A Grakoui. Contribution of the intestinal microbiome and gut barrier to hepatic disorders. Gastroenterology 2020; 159(3): 849–863 https://doi.org/10.1053/j.gastro.2020.04.077 pmid: 32569766
41	H Plovier, A Everard, C Druart, C Depommier, M Van Hul, L Geurts, J Chilloux, N Ottman, T Duparc, L Lichtenstein, A Myridakis, NM Delzenne, J Klievink, A Bhattacharjee, KC van der Ark, S Aalvink, LO Martinez, ME Dumas, D Maiter, A Loumaye, MP Hermans, JP Thissen, C Belzer, WM de Vos, PD Cani. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med 2017; 23(1): 107–113 https://doi.org/10.1038/nm.4236 pmid: 27892954
42	HS Yoon, CH Cho, MS Yun, SJ Jang, HJ You, JH Kim, D Han, KH Cha, SH Moon, K Lee, YJ Kim, SJ Lee, TW Nam, G Ko. Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nat Microbiol 2021; 6(5): 563–573 https://doi.org/10.1038/s41564-021-00880-5 pmid: 33820962
43	JJ Holst, CF Deacon, T Vilsbøll, T Krarup, S Madsbad. Glucagon-like peptide-1, glucose homeostasis and diabetes. Trends Mol Med 2008; 14(4): 161–168 https://doi.org/10.1016/j.molmed.2008.01.003 pmid: 18353723
44	Z Shi, H Lei, G Chen, P Yuan, Z Cao, HL Ser, X Zhu, F Wu, C Liu, M Dong, Y Song, Y Guo, C Chen, K Hu, Y Zhu, XA Zeng, J Zhou, Y Lu, AD Patterson, L Zhang. Impaired intestinal Akkermansia muciniphila and aryl hydrocarbon receptor ligands contribute to nonalcoholic fatty liver disease in mice. mSystems 2021; 6(1): e00985–20 https://doi.org/10.1128/mSystems.00985-20 pmid: 33622853
45	H Wang, L Wang, Y Li, S Luo, J Ye, Z Lu, X Li, H Lu. The HIF-2α/PPARα pathway is essential for liraglutide-alleviated, lipid-induced hepatic steatosis. Biomed Pharmacother 2021; 140: 111778 https://doi.org/10.1016/j.biopha.2021.111778 pmid: 34062416
46	A Everard, V Lazarevic, N Gaïa, M Johansson, M Ståhlman, F Backhed, NM Delzenne, J Schrenzel, P François, PD Cani. Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity. ISME J 2014; 8(10): 2116–2130 https://doi.org/10.1038/ismej.2014.45 pmid: 24694712
47	P Mehrpouya-Bahrami, KN Chitrala, MS Ganewatta, C Tang, EA Murphy, RT Enos, KT Velazquez, J McCellan, M Nagarkatti, P Nagarkatti. Blockade of CB1 cannabinoid receptor alters gut microbiota and attenuates inflammation and diet-induced obesity. Sci Rep 2017; 7(1): 15645 https://doi.org/10.1038/s41598-017-15154-6 pmid: 29142285
48	JM Natividad, B Lamas, HP Pham, ML Michel, D Rainteau, C Bridonneau, G da Costa, J van Hylckama Vlieg, B Sovran, C Chamignon, J Planchais, ML Richard, P Langella, P Veiga, H Sokol. Bilophila wadsworthia aggravates high fat diet induced metabolic dysfunctions in mice. Nat Commun 2018; 9(1): 2802 https://doi.org/10.1038/s41467-018-05249-7 pmid: 30022049
49	A Hussain, MK Yadav, S Bose, JH Wang, D Lim, YK Song, SG Ko, H Kim. Daesiho-Tang is an effective herbal formulation in attenuation of obesity in mice through alteration of gene expression and modulation of intestinal microbiota. PLoS One 2016; 11(11): e0165483 https://doi.org/10.1371/journal.pone.0165483 pmid: 27812119
50	J Lee, JY Jang, MS Kwon, SK Lim, N Kim, J Lee, HK Park, M Yun, MY Shin, HE Jo, YJ Oh, BH Ryu, MY Ko, W Joo, HJ Choi. Mixture of two Lactobacillus plantarum strains modulates the gut microbiota structure and regulatory T cell response in diet-induced obese mice. Mol Nutr Food Res 2018; 62(24): e1800329 https://doi.org/10.1002/mnfr.201800329 pmid: 30362639
51	L Wang, Y Wu, L Zhuang, X Chen, H Min, S Song, Q Liang, AD Li, Q Gao. Puerarin prevents high-fat diet-induced obesity by enriching Akkermansia muciniphila in the gut microbiota of mice. PLoS One 2019; 14(6): e0218490 https://doi.org/10.1371/journal.pone.0218490 pmid: 31233515
52	M Schneeberger, A Everard, AG Gómez-Valadés, S Matamoros, S Ramírez, NM Delzenne, R Gomis, M Claret, PD Cani. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Sci Rep 2015; 5(1): 16643 https://doi.org/10.1038/srep16643 pmid: 26563823
53	JZ Ye, YT Li, WR Wu, D Shi, DQ Fang, LY Yang, XY Bian, JJ Wu, Q Wang, XW Jiang, CG Peng, WC Ye, PC Xia, LJ Li. Dynamic alterations in the gut microbiota and metabolome during the development of methionine-choline-deficient diet-induced nonalcoholic steatohepatitis. World J Gastroenterol 2018; 24(23): 2468–2481 https://doi.org/10.3748/wjg.v24.i23.2468 pmid: 29930468
54	LK Brahe, E Le Chatelier, E Prifti, N Pons, S Kennedy, T Hansen, O Pedersen, A Astrup, SD Ehrlich, LH Larsen. Specific gut microbiota features and metabolic markers in postmenopausal women with obesity. Nutr Diabetes 2015; 5(6): e159 https://doi.org/10.1038/nutd.2015.9 pmid: 26075636
55	X Zhang, D Shen, Z Fang, Z Jie, X Qiu, C Zhang, Y Chen, L Ji. Human gut microbiota changes reveal the progression of glucose intolerance. PLoS One 2013; 8(8): e71108 https://doi.org/10.1371/journal.pone.0071108 pmid: 24013136
56	M Yassour, MY Lim, HS Yun, TL Tickle, J Sung, YM Song, K Lee, EA Franzosa, XC Morgan, D Gevers, ES Lander, RJ Xavier, BW Birren, G Ko, C Huttenhower. Sub-clinical detection of gut microbial biomarkers of obesity and type 2 diabetes. Genome Med 2016; 8(1): 17 https://doi.org/10.1186/s13073-016-0271-6 pmid: 26884067
57	J Li, F Zhao, Y Wang, J Chen, J Tao, G Tian, S Wu, W Liu, Q Cui, B Geng, W Zhang, R Weldon, K Auguste, L Yang, X Liu, L Chen, X Yang, B Zhu, J Cai. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome 2017; 5(1): 14 https://doi.org/10.1186/s40168-016-0222-x pmid: 28143587
58	MC Dao, A Everard, J Aron-Wisnewsky, N Sokolovska, E Prifti, EO Verger, BD Kayser, F Levenez, J Chilloux, L Hoyles, Consortium; Dumas ME MICRO-Obes, SW Rizkalla, J Doré, PD Cani, K Clément. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut 2016; 65(3): 426–436 https://doi.org/10.1136/gutjnl-2014-308778 pmid: 26100928
59	L Hoyles, JM Fernández-Real, M Federici, M Serino, J Abbott, J Charpentier, C Heymes, JL Luque, E Anthony, RH Barton, J Chilloux, A Myridakis, L Martinez-Gili, JM Moreno-Navarrete, F Benhamed, V Azalbert, V Blasco-Baque, J Puig, G Xifra, W Ricart, C Tomlinson, M Woodbridge, M Cardellini, F Davato, I Cardolini, O Porzio, P Gentileschi, F Lopez, F Foufelle, SA Butcher, E Holmes, JK Nicholson, C Postic, R Burcelin, ME Dumas. Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women. Nat Med 2018; 24(7): 1070–1080 https://doi.org/10.1038/s41591-018-0061-3 pmid: 29942096
60	E Nistal, de Miera LE Sáenz, Pomar M Ballesteros, S Sánchez-Campos, MV García-Mediavilla, B Álvarez-Cuenllas, P Linares, JL Olcoz, MT Arias-Loste, JM García-Lobo, J Crespo, J González-Gallego, Plaza F Jorquera. An altered fecal microbiota profile in patients with non-alcoholic fatty liver disease (NAFLD) associated with obesity. Rev Esp Enferm Dig 2019; 111(4): 275–282 https://doi.org/10.17235/reed.2019.6068/2018 pmid: 30810328
61	HJ Tsai, YC Tsai, WW Hung, WC Hung, CC Chang, CY Dai. Gut microbiota and non-alcoholic fatty liver disease severity in type 2 diabetes patients. J Pers Med 2021; 11(3): 238 https://doi.org/10.3390/jpm11030238 pmid: 33807075
62	NY Lee, MJ Shin, GS Youn, SJ Yoon, YR Choi, HS Kim, H Gupta, SH Han, BK Kim, DY Lee, TS Park, H Sung, BY Kim, KT Suk. Lactobacillus attenuates progression of nonalcoholic fatty liver disease by lowering cholesterol and steatosis. Clin Mol Hepatol 2021; 27(1): 110–124 https://doi.org/10.3350/cmh.2020.0125 pmid: 33317254
63	C Özkul, M Yalınay, T Karakan, G Yılmaz. Determination of certain bacterial groups in gut microbiota and endotoxin levels in patients with nonalcoholic steatohepatitis. Turk J Gastroenterol 2017; 28(5): 361–369 https://doi.org/10.5152/tjg.2017.17033 pmid: 28705785
64	Chierico F Del, V Nobili, P Vernocchi, A Russo, Stefanis C De, D Gnani, C Furlanello, A Zandonà, P Paci, G Capuani, B Dallapiccola, A Miccheli, A Alisi, L Putignani. Gut microbiota profiling of pediatric nonalcoholic fatty liver disease and obese patients unveiled by an integrated meta-omics-based approach. Hepatology 2017; 65(2): 451–464 https://doi.org/10.1002/hep.28572 pmid: 27028797
65	X Pan, AC Kaminga, A Liu, SW Wen, M Luo, J Luo. Gut microbiota, glucose, lipid, and water-electrolyte metabolism in children with nonalcoholic fatty liver disease. Front Cell Infect Microbiol 2021; 11: 683743 https://doi.org/10.3389/fcimb.2021.683743 pmid: 34778099
66	JB Schwimmer, JS Johnson, JE Angeles, C Behling, PH Belt, I Borecki, C Bross, J Durelle, NP Goyal, G Hamilton, ML Holtz, JE Lavine, M Mitreva, KP Newton, A Pan, PM Simpson, CB Sirlin, E Sodergren, R Tyagi, KP Yates, GM Weinstock, NH Salzman. Microbiome signatures associated with steatohepatitis and moderate to severe fibrosis in children with nonalcoholic fatty liver disease. Gastroenterology 2019; 157(4): 1109–1122 https://doi.org/10.1053/j.gastro.2019.06.028 pmid: 31255652
67	FR Ponziani, S Bhoori, C Castelli, L Putignani, L Rivoltini, F Del Chierico, M Sanguinetti, D Morelli, F Paroni Sterbini, V Petito, S Reddel, R Calvani, C Camisaschi, A Picca, A Tuccitto, A Gasbarrini, M Pompili, V Mazzaferro. Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease. Hepatology 2019; 69(1): 107–120 https://doi.org/10.1002/hep.30036 pmid: 29665135
68	R Liu, J Hong, X Xu, Q Feng, D Zhang, Y Gu, J Shi, S Zhao, W Liu, X Wang, H Xia, Z Liu, B Cui, P Liang, L Xi, J Jin, X Ying, X Wang, X Zhao, W Li, H Jia, Z Lan, F Li, R Wang, Y Sun, M Yang, Y Shen, Z Jie, J Li, X Chen, H Zhong, H Xie, Y Zhang, W Gu, X Deng, B Shen, X Xu, H Yang, G Xu, Y Bi, S Lai, J Wang, L Qi, L Madsen, J Wang, G Ning, K Kristiansen, W Wang. Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention. Nat Med 2017; 23(7): 859–868 https://doi.org/10.1038/nm.4358 pmid: 28628112
69	AS Lihn, SB Pedersen, B Richelsen. Adiponectin: action, regulation and association to insulin sensitivity. Obes Rev 2005; 6(1): 13–21 https://doi.org/10.1111/j.1467-789X.2005.00159.x pmid: 15655035
70	K Kordy, F Li, DJ Lee, JM Kinchen, MH Jew, ME La Rocque, S Zabih, M Saavedra, C Woodward, NJ Cunningham, NH Tobin, GM Aldrovandi. Metabolomic predictors of non-alcoholic steatohepatitis and advanced fibrosis in children. Front Microbiol 2021; 12: 713234 https://doi.org/10.3389/fmicb.2021.713234 pmid: 34475864
71	CK Negi, P Babica, L Bajard, J Bienertova-Vasku, G Tarantino. Insights into the molecular targets and emerging pharmacotherapeutic interventions for nonalcoholic fatty liver disease. Metabolism 2022; 126: 154925 https://doi.org/10.1016/j.metabol.2021.154925 pmid: 34740573
72	GV Moreira, FF Azevedo, LM Ribeiro, A Santos, D Guadagnini, P Gama, EA Liberti, M Saad, C Carvalho. Liraglutide modulates gut microbiota and reduces NAFLD in obese mice. J Nutr Biochem 2018; 62: 143–154 https://doi.org/10.1016/j.jnutbio.2018.07.009 pmid: 30292107
73	J Du, P Zhang, J Luo, L Shen, S Zhang, H Gu, J He, L Wang, X Zhao, M Gan, L Yang, L Niu, Y Zhao, Q Tang, G Tang, D Jiang, Y Jiang, M Li, A Jiang, L Jin, J Ma, S Shuai, L Bai, J Wang, B Zeng, D Wu, X Li, L Zhu. Dietary betaine prevents obesity through gut microbiota-drived microRNA-378a family. Gut Microbes 2021; 13(1): 1862612 https://doi.org/10.1080/19490976.2020.1862612 pmid: 33550882
74	L Zhang, Y Wang, F Wu, X Wang, Y Feng, Y Wang. MDG, an Ophiopogon japonicus polysaccharide, inhibits non-alcoholic fatty liver disease by regulating the abundance of Akkermansia muciniphila. Int J Biol Macromol 2022; 196: 23–34 https://doi.org/10.1016/j.ijbiomac.2021.12.036 pmid: 34920070
75	X Wang, D Liu, Z Wang, C Cai, H Jiang, G Yu. Porphyran-derived oligosaccharides alleviate NAFLD and related cecal microbiota dysbiosis in mice. FASEB J 2021; 35(6): e21458 https://doi.org/10.1096/fj.202000763RRR pmid: 33948987
76	R Han, H Qiu, J Zhong, N Zheng, B Li, Y Hong, J Ma, G Wu, L Chen, L Sheng, H Li. Si Miao Formula attenuates non-alcoholic fatty liver disease by modulating hepatic lipid metabolism and gut microbiota. Phytomedicine 2021; 85: 153544 https://doi.org/10.1016/j.phymed.2021.153544 pmid: 33773192
77	S Ghosh, X Yang, L Wang, C Zhang, L Zhao. Active phase prebiotic feeding alters gut microbiota, induces weight-independent alleviation of hepatic steatosis and serum cholesterol in high-fat diet-fed mice. Comput Struct Biotechnol J 2021; 19: 448–458 https://doi.org/10.1016/j.csbj.2020.12.011 pmid: 33510856
78	X Hua, DY Sun, WJ Zhang, JT Fu, J Tong, SJ Sun, FY Zeng, SX Ouyang, GY Zhang, SN Wang, DJ Li, CY Miao, P Wang. P7C3-A20 alleviates fatty liver by shaping gut microbiota and inducing FGF21/FGF1, via the AMP-activated protein kinase/CREB regulated transcription coactivator 2 pathway. Br J Pharmacol 2021; 178(10): 2111–2130 https://doi.org/10.1111/bph.15008 pmid: 32037512
79	T Bao, F He, X Zhang, L Zhu, Z Wang, H Lu, T Wang, Y Li, S Yang, H Wang. Inulin exerts beneficial effects on non-alcoholic fatty liver disease via modulating gut microbiome and suppressing the lipopolysaccharide-Toll-like receptor 4-Mψ-nuclear factor-κB-Nod-like receptor protein 3 pathway via gut-liver axis in mice. Front Pharmacol 2020; 11: 558525 https://doi.org/10.3389/fphar.2020.558525 pmid: 33390939
80	H Cui, Y Li, Y Wang, L Jin, L Yang, L Wang, J Liao, H Wang, Y Peng, Z Zhang, H Wang, X Liu. Da-Chai-Hu Decoction ameliorates high fat diet-induced nonalcoholic fatty liver disease through remodeling the gut microbiota and modulating the serum metabolism. Front Pharmacol 2020; 11: 584090 https://doi.org/10.3389/fphar.2020.584090 pmid: 33328987
81	H Nakano, S Wu, K Sakao, T Hara, J He, S Garcia, K Shetty, DX Hou. Bilberry anthocyanins ameliorate NAFLD by improving dyslipidemia and gut microbiome dysbiosis. Nutrients 2020; 12(11): 3252 https://doi.org/10.3390/nu12113252 pmid: 33114130
82	J Mu, F Tan, X Zhou, X Zhao. Lactobacillus fermentum CQPC06 in naturally fermented pickles prevents non-alcoholic fatty liver disease by stabilizing the gut-liver axis in mice. Food Funct 2020; 11(10): 8707–8723 https://doi.org/10.1039/D0FO01823F pmid: 32945305
83	K Xie, X He, K Chen, K Sakao, DX Hou. Ameliorative effects and molecular mechanisms of vine tea on western diet-induced NAFLD. Food Funct 2020; 11(7): 5976–5991 https://doi.org/10.1039/D0FO00795A pmid: 32666969
84	M Nishiyama, N Ohtake, A Kaneko, N Tsuchiya, S Imamura, S Iizuka, S Ishizawa, A Nishi, M Yamamoto, A Taketomi, T Kono. Increase of Akkermansia muciniphila by a diet containing Japanese traditional medicine bofutsushosan in a mouse model of non-alcoholic fatty liver disease. Nutrients 2020; 12(3): 839 https://doi.org/10.3390/nu12030839 pmid: 32245128
85	X Li, Y Wang, Y Xing, R Xing, Y Liu, Y Xu. Changes of gut microbiota during silybin-mediated treatment of high-fat diet-induced non-alcoholic fatty liver disease in mice. Hepatol Res 2020; 50(1): 5–14 https://doi.org/10.1111/hepr.13444 pmid: 31661720
86	D Porras, E Nistal, S Martínez-Flórez, JL Olcoz, R Jover, F Jorquera, J González-Gallego, MV García-Mediavilla, S Sánchez-Campos. Functional interactions between gut microbiota transplantation, quercetin, and high-fat diet determine non-alcoholic fatty liver disease development in germ-free mice. Mol Nutr Food Res 2019; 63(8): e1800930 https://doi.org/10.1002/mnfr.201800930 pmid: 30680920
87	M Régnier, M Rastelli, A Morissette, F Suriano, Roy T Le, G Pilon, NM Delzenne, A Marette, Hul M Van, PD Cani. Rhubarb supplementation prevents diet-induced obesity and diabetes in association with increased Akkermansia muciniphila in mice. Nutrients 2020; 12(10): 2932 https://doi.org/10.3390/nu12102932 pmid: 32987923
88	M Juárez-Fernández, D Porras, P Petrov, S Román-Sagüillo, MV García-Mediavilla, P Soluyanova, S Martínez-Flórez, J González-Gallego, E Nistal, R Jover, S Sánchez-Campos. The synbiotic combination of Akkermansia muciniphila and quercetin ameliorates early obesity and NAFLD through gut microbiota reshaping and bile acid metabolism modulation. Antioxidants (Basel) 2021; 10(12): 2001 https://doi.org/10.3390/antiox10122001 pmid: 34943104
89	M Guevara-Cruz, AG Flores-López, M Aguilar-López, M Sánchez-Tapia, I Medina-Vera, D Díaz, AR Tovar, N Torres. Improvement of lipoprotein profile and metabolic endotoxemia by a lifestyle intervention that modifies the gut microbiota in subjects with metabolic syndrome. J Am Heart Assoc 2019; 8(17): e012401 https://doi.org/10.1161/JAHA.119.012401 pmid: 31451009
90	A Palleja, A Kashani, KH Allin, T Nielsen, C Zhang, Y Li, T Brach, S Liang, Q Feng, NB Jørgensen, KN Bojsen-Møller, C Dirksen, KS Burgdorf, JJ Holst, S Madsbad, J Wang, O Pedersen, T Hansen, M Arumugam. Roux-en-Y gastric bypass surgery of morbidly obese patients induces swift and persistent changes of the individual gut microbiota. Genome Med 2016; 8(1): 67 https://doi.org/10.1186/s13073-016-0312-1 pmid: 27306058
91	C Depommier, M Van Hul, A Everard, NM Delzenne, WM De Vos, PD Cani. Pasteurized Akkermansia muciniphila increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice. Gut Microbes 2020; 11(5): 1231–1245 https://doi.org/10.1080/19490976.2020.1737307 pmid: 32167023
92	SG Higarza, S Arboleya, JL Arias, M Gueimonde, N Arias. Akkermansia muciniphila and environmental enrichment reverse cognitive impairment associated with high-fat high-cholesterol consumption in rats. Gut Microbes 2021; 13(1): 1880240 https://doi.org/10.1080/19490976.2021.1880240 pmid: 33678110
93	Y Yang, Z Zhong, B Wang, X Xia, W Yao, L Huang, Y Wang, W Ding. Early-life high-fat diet-induced obesity programs hippocampal development and cognitive functions via regulation of gut commensal Akkermansia muciniphila. Neuropsychopharmacology 2019; 44(12): 2054–2064 https://doi.org/10.1038/s41386-019-0437-1 pmid: 31207607
94	M Eslam, AJ Sanyal, Jnternational Consensus Panel George;. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology 2020; 158(7): 1999–2014.e1 https://doi.org/10.1053/j.gastro.2019.11.312 pmid: 32044314
95	R Lomonaco, C Ortiz-Lopez, B Orsak, A Webb, J Hardies, C Darland, J Finch, A Gastaldelli, S Harrison, F Tio, K Cusi. Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease. Hepatology 2012; 55(5): 1389–1397 https://doi.org/10.1002/hep.25539 pmid: 22183689
96	RS Khan, PN Newsome. NAFLD in 2017: novel insights into mechanisms of disease progression. Nat Rev Gastroenterol Hepatol 2018; 15(2): 71–72 https://doi.org/10.1038/nrgastro.2017.181 pmid: 29300050
97	F Ashrafian, A Shahriary, A Behrouzi, HR Moradi, S Keshavarz Azizi Raftar, A Lari, S Hadifar, R Yaghoubfar, S Ahmadi Badi, S Khatami, F Vaziri, SD Siadat. Akkermansia muciniphila-derived extracellular vesicles as a mucosal delivery vector for amelioration of obesity in mice. Front Microbiol 2019; 10: 2155 https://doi.org/10.3389/fmicb.2019.02155 pmid: 31632356
98	J Shen, X Tong, N Sud, R Khound, Y Song, MX Maldonado-Gomez, J Walter, Q Su. Low-density lipoprotein receptor signaling mediates the triglyceride-lowering action of Akkermansia muciniphila in genetic-induced hyperlipidemia. Arterioscler Thromb Vasc Biol 2016; 36(7): 1448–1456 https://doi.org/10.1161/ATVBAHA.116.307597 pmid: 27230129
99	S Zhao, W Liu, J Wang, J Shi, Y Sun, W Wang, G Ning, R Liu, J Hong. Akkermansia muciniphila improves metabolic profiles by reducing inflammation in chow diet-fed mice. J Mol Endocrinol 2017; 58(1): 1–14 https://doi.org/10.1530/JME-16-0054 pmid: 27821438
100	X Gao, Q Xie, P Kong, L Liu, S Sun, B Xiong, B Huang, L Yan, J Sheng, H Xiang. Polyphenol- and caffeine-rich postfermented Pu-erh Tea improves diet-induced metabolic syndrome by remodeling intestinal homeostasis in mice. Infect Immun 2018; 86(1): e00601–17 https://doi.org/10.1128/IAI.00601-17 pmid: 29061705
101	L Sheng, PK Jena, HX Liu, Y Hu, N Nagar, DN Bronner, ML Settles, AJ Bäumler, YY Wan. Obesity treatment by epigallocatechin-3-gallate-regulated bile acid signaling and its enriched Akkermansia muciniphila. FASEB J 2018; 32(12): fj201800370R https://doi.org/10.1096/fj.201800370R pmid: 29882708
102	S Katiraei, Vries MR de, AH Costain, K Thiem, LR Hoving, Diepen JA van, HH Smits, KE Bouter, PCN Rensen, PHA Quax, M Nieuwdorp, MG Netea, Vos WM de, PD Cani, C Belzer, Dijk KW van, JFP Berbée, Harmelen V van. Akkermansia muciniphila exerts lipid-lowering and immunomodulatory effects without affecting neointima formation in hyperlipidemic APOE*3-Leiden. CETP mice. Mol Nutr Food Res 2020; 64(15): e1900732 https://doi.org/10.1002/mnfr.201900732 pmid: 31389129
103	H Lee, Y Lee, J Kim, J An, S Lee, H Kong, Y Song, CK Lee, K Kim. Modulation of the gut microbiota by metformin improves metabolic profiles in aged obese mice. Gut Microbes 2018; 9(2): 155–165 https://doi.org/10.1080/19490976.2017.1405209 pmid: 29157127
104	H Tilg. The role of cytokines in non-alcoholic fatty liver disease. Dig Dis 2010; 28(1): 179–185 https://doi.org/10.1159/000282083 pmid: 20460908
105	G Carpino, M Del Ben, D Pastori, R Carnevale, F Baratta, D Overi, H Francis, V Cardinale, P Onori, S Safarikia, V Cammisotto, D Alvaro, G Svegliati-Baroni, F Angelico, E Gaudio, F Violi. Increased liver localization of lipopolysaccharides in human and experimental NAFLD. Hepatology 2020; 72(2): 470–485 https://doi.org/10.1002/hep.31056 pmid: 31808577
106	T Sharifnia, J Antoun, TG Verriere, G Suarez, J Wattacheril, KT Wilson, RM Jr Peek, NN Abumrad, CR Flynn. Hepatic TLR4 signaling in obese NAFLD. Am J Physiol Gastrointest Liver Physiol 2015; 309(4): G270–G278 https://doi.org/10.1152/ajpgi.00304.2014 pmid: 26113297
107	C Michaudel, H Sokol. The gut microbiota at the service of immunometabolism. Cell Metab 2020; 32(4): 514–523 https://doi.org/10.1016/j.cmet.2020.09.004 pmid: 32946809
108	J Cai, XJ Zhang, H Li. Role of innate immune signaling in non-alcoholic fatty liver disease. Trends Endocrinol Metab 2018; 29(10): 712–722 https://doi.org/10.1016/j.tem.2018.08.003 pmid: 30131212
109	K Miura, L Yang, N van Rooijen, DA Brenner, H Ohnishi, E Seki. Toll-like receptor 2 and palmitic acid cooperatively contribute to the development of nonalcoholic steatohepatitis through inflammasome activation in mice. Hepatology 2013; 57(2): 577–589 https://doi.org/10.1002/hep.26081 pmid: 22987396
110	K Kazankov, SMD Jørgensen, KL Thomsen, HJ Møller, H Vilstrup, J George, D Schuppan, H Grønbæk. The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Nat Rev Gastroenterol Hepatol 2019; 16(3): 145–159 https://doi.org/10.1038/s41575-018-0082-x pmid: 30482910
111	X Yang, H Liu, T Ye, C Duan, P Lv, X Wu, J Liu, K Jiang, H Lu, H Yang, D Xia, E Peng, Z Chen, K Tang, Z Ye. AhR activation attenuates calcium oxalate nephrocalcinosis by diminishing M1 macrophage polarization and promoting M2 macrophage polarization. Theranostics 2020; 10(26): 12011–12025 https://doi.org/10.7150/thno.51144 pmid: 33204326
112	Y Huang, J He, H Liang, K Hu, S Jiang, L Yang, S Mei, X Zhu, J Yu, A Kijlstra, P Yang, S Hou. Aryl Hydrocarbon receptor regulates apoptosis and inflammation in a murine model of experimental autoimmune uveitis. Front Immunol 2018; 9: 1713 https://doi.org/10.3389/fimmu.2018.01713 pmid: 30090104
113	Z Cui, Y Feng, D Li, T Li, P Gao, T Xu. Activation of aryl hydrocarbon receptor (AhR) in mesenchymal stem cells modulates macrophage polarization in asthma. J Immunotoxicol 2020; 17(1): 21–30 https://doi.org/10.1080/1547691X.2019.1706671 pmid: 31922435
114	KW Bock. Aryl hydrocarbon receptor (AHR)-mediated inflammation and resolution: non-genomic and genomic signaling. Biochem Pharmacol 2020; 182: 114220 https://doi.org/10.1016/j.bcp.2020.114220 pmid: 32941865
115	YH Lin, H Luck, S Khan, PHH Schneeberger, S Tsai, X Clemente-Casares, H Lei, YL Leu, YT Chan, HY Chen, SH Yang, B Coburn, S Winer, DA Winer. Aryl hydrocarbon receptor agonist indigo protects against obesity-related insulin resistance through modulation of intestinal and metabolic tissue immunity. Int J Obes 2019; 43(12): 2407–2421 https://doi.org/10.1038/s41366-019-0340-1 pmid: 30944419
116	T Wada, H Sunaga, K Miyata, H Shirasaki, Y Uchiyama, S Shimba. Aryl hydrocarbon receptor plays protective roles against high fat diet (HFD)-induced hepatic steatosis and the subsequent lipotoxicity via direct transcriptional regulation of Socs3 gene expression. J Biol Chem 2016; 291(13): 7004–7016 https://doi.org/10.1074/jbc.M115.693655 pmid: 26865635
117	F Yang, JAA DeLuca, R Menon, E Garcia-Vilarato, E Callaway, KK Landrock, K Lee, SH Safe, RS Chapkin, CD Allred, A Jayaraman. Effect of diet and intestinal AhR expression on fecal microbiome and metabolomic profiles. Microb Cell Fact 2020; 19(1): 219 https://doi.org/10.1186/s12934-020-01463-5 pmid: 33256731
118	SKA Raftar, F Ashrafian, S Abdollahiyan, A Yadegar, HR Moradi, M Masoumi, F Vaziri, A Moshiri, SD Siadat, MR Zali. The anti-inflammatory effects of Akkermansia muciniphila and its derivates in HFD/CCl4-induced murine model of liver injury. Sci Rep 2022; 12(1): 2453 https://doi.org/10.1038/s41598-022-06414-1 pmid: 35165344

Viewed

Full text

Abstract

Cited

Shared

Discussed