Akkermansia muciniphila: a potential booster to improve the effectiveness of cancer immunotherapy

Fan, ST; Jiang, Zhengting; Zhang, Zhilin; Xing, Juan; Wang, Daorong; Tang, Dong

doi:10.1007/s00432-023-05199-8

Cited by 8 publications

(4 citation statements)

References 100 publications

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“…Stool analysis over 63 days revealed that Roseburia and Akkermansia genera were more abundant in the osteosarcoma group whereas Lachnospiraceae NK4A135 and Muribaculaceae were elevated in the control group [56] . Interestingly, literature predominately suggests a protective role of Roseburia and Akkermansia in cancer contrary to the results of this study [41] , [42] , [43] , [57] , [58] . It was hypothesized that the observed increases in butyrate synthesizing Roseburia and mucin degrading Akkermansia abundance may be a protective mechanism to restore bacterial diversity in the gut [56] .…”

Section: The Gut Microbiome and Cancer In The Bonecontrasting

confidence: 99%

“…In the non-cancer controls, Megamonas , Akkermansia, Clostridia, Gemmiger, and Paraprevotella were significantly more abundant [36] . Akkermansia manipulation has previously been shown to have a protective effect against cancer and increase treatment responsiveness in mice [41] , [42] , [43] . Megamonas has been found to be reduced in older adults with intestinal permeability [44] .…”

Section: The Gut Microbiome and Cancer In The Bonementioning

confidence: 99%

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Bones and guts – Why the microbiome matters

Contino,

Cook,

Shiozawa

2024

Journal of Bone Oncology

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Section: The Gut Microbiome and Cancer In The Bonecontrasting

confidence: 99%

Section: The Gut Microbiome and Cancer In The Bonementioning

confidence: 99%

Bones and guts – Why the microbiome matters

Contino,

Cook,

Shiozawa

2024

Journal of Bone Oncology

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“…Akkermansia muciniciphila ( A. muciniphila ), the most important species of the Akkermansia genus, is emerging as a potential immune booster, especially in cancer immunotherapy ( 12 , 38 , 39 ). Both short-chain fatty acids (SCFAs) and inosine, the vital metabolites of A. muciniphila , have been proven beneficial for tumor immunotherapy ( 34 , 40 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of inosine metabolism of the gut microbiota decreases testosterone secretion in the testis

Tang,

Yang,

Zhou

et al. 2024

mSystems

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Growing evidence indicates that gut microbiota is involved in the regulation of the host’s sex hormone levels, such as through interfering with the sex hormone metabolism in the intestine. However, if gut microbiota or its metabolites directly influence the sex hormone biosynthesis in the gonad remains largely unknown. Our previous study showed that colistin, as a narrow-spectrum antibiotic, can significantly downregulate the serum testosterone levels and thus enhance the antitumor efficiency of anti-PD-L1 in male mice; however, the underlying mechanism for the regulation of the host’s testosterone levels remains uninvestigated. In the present study, we analyzed the impact of colistin on the immune microenvironment of the testis as well as the composition and metabolism of gut microbiota in male mice. Our results showed that colistin has an impact on the immune microenvironment of the testis and can downregulate serum testosterone levels in male mice through inhibition of Akkermansia , leading to destroyed inosine metabolism. Supplement with inosine can restore testosterone secretion probably by prompting the recovery of the intestinal mucus barrier and the serum lipopolysaccharides levels. All these findings reveal a new pathway for the regulation of the host’s sex hormone levels by gut microbiota. IMPORTANCE This study demonstrates that exposure to even narrow-spectrum antibiotics may affect the host’s testosterone levels by altering the gut microbiota and its metabolites. Our findings provide evidence that some specific gut bacteria have an impact on the sex hormone biosynthesis in the testis.

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“…Notably, the fecal microbiota of patients with NSCLC had diminished levels of some beneficial bacteria, such as A. muciniphila, Oscillospiraceae bacteria, and Alistipes shahii. Some Oscillospiraceae are known to produce SCFAs [23], while A. muciniphila and Alistipes shahii are found to associate with the responsiveness and effectiveness of cancer immunotherapy [24,25]. Obvious differences in the predicted functional potential of the gut microbiota between the two groups of patients were also noted: the fecal microbiota of patients with NSCLC had fewer GMMs which encode pathways relating to the metabolism and biosynthesis of SCFAs, amino acids, and secondary bile acids compared with those of healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Changes of the Gut Microbiota and Its Functional Metagenomic Potential during the Development of Non-Small Cell Lung Cancer

Feng,

Li,

Gao

et al. 2024

IJMS

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The gut microbiota plays a significant role in tumor pathogenesis by regulating the host metabolism and immune response, and there are few studies focused on tracking changes in the gut microbiota from the onset of lung cancer. Therefore, the aim of our study is combining preclinical and clinical research to thoroughly analyze the signatures of fecal microbiota in lung cancer, which will be useful for early diagnosis and predicting the therapeutic efficacy of lung cancer. The first part of this study analyzed the fecal metagenomic differences between patients with non-small cell lung cancer and healthy subjects, and the second part of this work constructed a murine lung cancer model to monitor changes in mouse fecal metagenomics and T cell immunology during lung cancer progression. We found that the fecal microbiota was altered in both humans and mice with lung cancer, characterized by a significantly reduced microbial diversity and number of beneficial microbes, with increases in potential pathogens. The fecal level of Akkermansia muciniphila and the gut metabolic module of the secondary bile acid metabolism were diminished in both humans and mice with lung cancer compared with healthy subjects. Splenomegaly was observed in the lung cancer mice. Flow cytometer analysis of the splenocytes revealed substantial alterations in the proportions of T cell subsets in the lung cancer mice, characterized by significant increases in CD4+Foxp3+CD25+ T regulatory cells (p < 0.05) while significant decreases in CD3+ T cells (p < 0.001), CD4+ T cells (p < 0.001), and the CD4+/CD8+ ratio (p < 0.01). Vertical and longitudinal analyses of the fecal microbiota of the two mouse groups identified some lung cancer biomarkers (including Acutalibacter timonensis, Lachnospiraceae bacterium NSJ-38 sp014337195, etc.). The fecal microbiota of the lung cancer mice had a reduced metagenomic potential for neurotransmitters (melatonin, γ-aminobutyric acid, and histamine) compared with healthy mice. In summary, this study found that the diversity, structure, and composition of gut microbiota vary between cancer and healthy conditions, ultimately leading to changes in the potential for functional metagenomics.

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Akkermansia muciniphila: a potential booster to improve the effectiveness of cancer immunotherapy

Cited by 8 publications

References 100 publications

Bones and guts – Why the microbiome matters

Bones and guts – Why the microbiome matters

Inhibition of inosine metabolism of the gut microbiota decreases testosterone secretion in the testis

Dynamic Changes of the Gut Microbiota and Its Functional Metagenomic Potential during the Development of Non-Small Cell Lung Cancer

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