1887

Abstract

Considerable progress has been made in understanding the roles of in inflammation and gastric cancer; however, far less is known about the roles of enterohepatic species (EHS) in carcinogenesis and their zoonotic or pathogenic potential. We determined the prevalence of EHS infection in a cohort of geriatric rhesus monkeys in which intestinal adenocarcinoma (IAC) is common and investigated the association between EHS infection and IAC. The cohort consisted of 36 animals, 14 of which (age 26–35 years) had IAC. Of the 36 rhesus, 35 (97 %) were positive for EHS using PCR or bacterial isolation from faeces, colonic or tumour tissues. Only a single rhesus, which had IAC, was negative for EHS by all detection methods. The EHS identified by 16S rRNA sequencing in this study were from three taxa: (previously rhesus monkey taxon 1), sp. rhesus monkey taxon 2, previously described from strain MIT 99-5507, and sp. rhesus monkey taxon 4, related to . Thirteen of 14 monkeys with IAC were positive for either (7/13, 54 %), EHS rhesus monkey taxon 4 (4/13, 31 %) or a mixture of the two EHS (2/13, 15 %). These results indicate that EHS are prevalent among aged rhesus macaques with IAC. Using genus-specific florescent hybridization, EHS were detected on the surface of colonic epithelia of infected monkeys. All isolates, including , effectively adhered to, invaded, and significantly induced proinflammatory genes, including , , α and , while downregulating genes involved in the function of inflammasomes, particularly β and in the human colonic T84 cell line (<0.0001). These results suggest that EHS may represent an aetiological agent mediating diarrhoea, chronic inflammation, and possibly intestinal cancer in non-human primates, and may play a role in similar disease syndromes in humans. Downregulation of inflammasome function may represent an EHS strategy for long-term persistence in the host and play a role in inducing pathological changes in the host’s lower bowel.

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2014-07-01
2020-01-29
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