Neutrophils Restrict Tumor-Associated Microbiota to Reduce Growth and Invasion of Colon Tumors in Mice

Triner, Daniel; Devenport, Samantha; Ramakrishnan, S; Ma, Xiaoya; Frieler, Ryan A.; Greenson, Joel K.; Inohara, Naohiro; Núñez, Gabriel; Colacino, Justin A.; Mortensen, Richard M.; Shah, Yatrik M.

doi:10.1053/j.gastro.2018.12.003

Cited by 94 publications

(84 citation statements)

References 59 publications

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“…A recent study indicated that neutrophil deletion leads to sporadic colon tumorigenesis with increased bacterial growth in the tumor, proliferation of tumor cell, and inflammatory response mediated by interleukin 17 . 16S rRNA‐sequencing data suggested that dysbiosis of gut microbiota, especially that of the Clostridiales and A muciniphila , significantly contributed to the development and progression of tumor in neutrophil‐deficient mice . It is interesting that some bacteria play an essential role in the host, even at low abundance.…”

Section: Discussionmentioning

confidence: 99%

“…48 16S rRNA-sequencing data suggested that dysbiosis of gut microbiota, especially that of the Clostridiales and A muciniphila, significantly contributed to the development and progression of tumor in neutrophil-deficient mice. 48 It is interesting that some bacteria play an essential role in the host, even at low abundance. For example, Lactobacillus murinus, with less than ~1% relative abundance in mice, could prevent salt-induced aggravation of actively induced experimental autoimmune encephalomyelitis and salt-sensitive hypertension, by modulating TH17 cells.…”

Section: Discussionmentioning

confidence: 99%

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Fecal microbiota as a noninvasive biomarker to predict the tissue iron accumulation in intestine epithelial cells and liver

et al. 2020

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Iron is an essential trace mineral required for growth, metabolism, and immune response. Dysregulation of iron homeostasis is linked with the development and progression of various diseases. Iron accumulation is associated with inflammatory diseases and cancer, while iron deficiency leads to the growth retardation. Several studies have suggested that iron imbalance results in alteration of gut microbiota, leading to the disruption of microbial diversity, the increase of pathogen abundance, and the induction of intestinal inflammation. However, in screening studies done in the past decades, the association between the iron availability and gut microbiota has not been systemically explored. Furthermore, a noninvasive and convenient approach to determine the iron levels in tissues is lacking. In the present study, a murine model for iron dysregulation was established. 16S rRNA amplicon sequencing and bioinformatic algorithms were used to identify the key taxa. Using the key taxa identified and machine learning models, we established an easily accessible prediction model, which could accurately distinguish between iron-deprived or ironfortified condition. This prediction model could precisely predict the iron level of the intestinal epithelial cells and the liver and could be used for early diagnosis of iron dysbiosis-related diseases, in a noninvasive manner, in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fecal microbiota as a noninvasive biomarker to predict the tissue iron accumulation in intestine epithelial cells and liver

et al. 2020

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“…LASSO regression model further confirmed the essential connection between the identified microbiota and the tissue iron with a high confidential rate. (41). Clostridium_perfringens is another member of Clostridiaceae family in human and animal intestine and is associated with various systemic and enteric diseases such as diarrhea, colitis, and colon cancer (42).…”

Section: Discussionmentioning

confidence: 99%

Fecal microbiota as a non-invasive biomarker to predict the tissue iron accumulation in intestine epithelial cells and liver

Liu

Pan

Yao

et al. 2019

Preprint

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Iron is an essential trace mineral required for growth, metabolism, and immune response. Dysregulation of iron homeostasis is linked with the development and progression of various diseases. Iron accumulation is associated with inflammatory diseases and cancer, while iron deficiency leads to the growth retardation. Several studies have suggested that iron imbalance results in alteration of gut microbiota, leading to the disruption of microbial diversity, the increase of pathogen abundance, and the induction of intestinal inflammation. However, in screening studies done in the past decades, the association between the iron availability and gut microbiota has not been systemically explored. Furthermore, a noninvasive and convenient approach to determine the iron levels in tissues is lacking. In the present study, a murine model for iron dysregulation was established. 16S rRNA amplicon sequencing and bioinformatic algorithms were used to identify the key taxa. Using the key taxa identified and machine learning models, we established an easily accessible prediction model, which could accurately distinguish between iron‐deprived or iron‐fortified condition. This prediction model could precisely predict the iron level of the intestinal epithelial cells and the liver and could be used for early diagnosis of iron dysbiosis‐related diseases, in a noninvasive manner, in the future.

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“…In mice bearing CRC xenograft, treatment with metronidazole eradicates Fusobacterium colonization, and reduces CRC proliferation [88], suggesting antibiotics as a potential intervention for Fusobacterium-enriched CRC patients. Another study that investigated in the role of neutrophils in colon tumors has reported a distinct microbiota composition in mice with or without neutrophil depletion, whereas antibiotics treatment reduces bacterial load in tumor and inhibits tumor invasion [89]. Meanwhile, antibiotics treatment is even suggested as an immunotherapeutic strategy, as gut microbiome depletion by antibiotics was shown to elicit antitumor immune response and suppresses tumor growth in metastatic mouse models [90].…”

Section: Depletion Of Deleterious Bacteriamentioning

confidence: 99%

“…In animal models, antibiotic treatment is a common strategy employed to eradicate carcinogenic bacteria, and by doing so, antibiotic administration is often reported to protect against cancer development or attenuate tumor proliferation in these studies [82,89]. Clinical studies, however, have reported disparate findings that antibiotic use is closely associated with increased risk of CRC development, instead of a protective effect [98,99].…”

Section: Induction or Exacerbation Of Dysbiosismentioning

confidence: 99%

Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer

2020

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Research about the role of gut microbiome in colorectal cancer (CRC) is a newly emerging field of study. Gut microbiota modulation, with the aim to reverse established microbial dysbiosis, is a novel strategy for prevention and treatment of CRC. Different strategies including probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT) have been employed. Although these strategies show promising results, mechanistically by correcting microbiota composition, modulating innate immune system, enhancing gut barrier function, preventing pathogen colonization and exerting selective cytotoxicity against tumor cells, it should be noted that they are accompanied by risks and controversies that can potentially introduce clinical complications. During bench-to-bedside translation, evaluation of risk-and-benefit ratio, as well as patient selection, should be carefully performed. In view of the individualized host response to gut microbiome intervention, developing personalized microbiome therapy may be the key to successful clinical treatment.

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Neutrophils Restrict Tumor-Associated Microbiota to Reduce Growth and Invasion of Colon Tumors in Mice

Abstract: Background & Aims: Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors, are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer. Trials of inhibitors of neutrophil

Cited by 94 publications

References 59 publications

Fecal microbiota as a noninvasive biomarker to predict the tissue iron accumulation in intestine epithelial cells and liver

Fecal microbiota as a noninvasive biomarker to predict the tissue iron accumulation in intestine epithelial cells and liver

Fecal microbiota as a non-invasive biomarker to predict the tissue iron accumulation in intestine epithelial cells and liver

Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer

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