Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-25965-x
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Funding
- Japan Agency of Medical Research and Development (AMED) [19gm501000h0003, 19cm0106401h0004]
- Japan Science and Technology Agency (JST) [JPMJMS2022]
- Japan Society for the Promotion of Science (JSPS) [19K16612, 18K15065, 16H06276, 26250028, 18K15188]
- Grants-in-Aid for Scientific Research [26250028, 18K15065, 19K16612, 18K15188] Funding Source: KAKEN
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Research has found that 12 bacterial taxa are enriched in CRC patients, with two Porphyromonas species accelerating CRC onset through butyrate secretion. The invasion of these bacteria in CRC tissues leads to elevated butyrate levels and senescence-associated inflammatory phenotypes.
Several bacteria in the gut microbiota have been associated with colorectal cancer (CRC) but it is not completely clear whether they have a role in tumourigenesis. Here, the authors show enrichment of 12 bacterial taxa in two cohorts of CRC patients and that two Porphyromonas species accelerate CRC onset through butyrate secretion. Emerging evidence is revealing that alterations in gut microbiota are associated with colorectal cancer (CRC). However, very little is currently known about whether and how gut microbiota alterations are causally associated with CRC development. Here we show that 12 faecal bacterial taxa are enriched in CRC patients in two independent cohort studies. Among them, 2 Porphyromonas species are capable of inducing cellular senescence, an oncogenic stress response, through the secretion of the bacterial metabolite, butyrate. Notably, the invasion of these bacteria is observed in the CRC tissues, coinciding with the elevation of butyrate levels and signs of senescence-associated inflammatory phenotypes. Moreover, although the administration of these bacteria into Apc(Delta 14/+) mice accelerate the onset of colorectal tumours, this is not the case when bacterial butyrate-synthesis genes are disrupted. These results suggest a causal relationship between Porphyromonas species overgrowth and colorectal tumourigenesis which may be due to butyrate-induced senescence.
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