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Int J Cancer. 2018 Apr 26. doi: 10.1002/ijc.31559. [Epub ahead of print]

Parabacteroides distasonis attenuates toll-like receptor 4 signaling and Akt activation and blocks colon tumor formation in high-fat diet-fed azoxymethane-treated mice.

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Jean Mayer USDA Human Nutrition Research on Aging at Tufts University, Boston, MA.
Phoenix Laboratory, Tufts Medical Center, Boston, MA.
Department of Chemical and Biological Engineering, Tufts University, Medford, MA.
Department of Biomedical Engineering, Tufts University, Medford, MA.
Tufts University School of Medicine, Boston, MA.
Friedman School of Nutrition Science and Policy, Boston, MA.


Gut dysbiosis may play an etiological role in colorectal tumorigenesis. We previously observed that the abundance of Parabacteroides distasonis (Pd) in stool was inversely associated with intestinal tumor burden and IL-1β concentrations in mice. Here, we assessed the anti-inflammatory capacity of Pd membrane fraction (PdMb) in colon cancer cell lines. In addition, we tested whether Pd could suppress colon tumorigenesis in mice. Six-week old male A/J mice were fed a low-fat diet (LF), high-fat diet (HF), or HF+ whole freeze-dried Pd (HF+Pd, 0.04% w/w) for 24 weeks. After 1 week on diet, mice received 4 weekly injections of azoxymethane (AOM). PdMb robustly suppressed the production of pro-inflammatory cytokines and lowered the abundance of MyD88 and pAkt (ser473) induced by E. coli lipopolysaccharide in colon cancer cell lines. Moreover, PdMb induced apoptosis in colon cancer cell lines and blocked TLR4 activation in a reporter line. Colon tumors were observed in 0% of LF (0 of 19), 25% of HF (5 of 20) and 0% of HF+Pd mice (0 of 20) (P = 0.005). The latter group also displayed a lower abundance of MyD88 and pAkt (ser473) in colonic mucosa than HF mice. Taken together, these data suggest that Pd has anti-inflammatory and anti-cancer properties that are likely mediated by the suppression of TLR4 and Akt signaling, as well as promotion of apoptosis. Further work is needed to confirm these findings in additional models and fully elaborate the mechanism of action. This article is protected by copyright. All rights reserved.


Parabacteroides distasonis; colorectal cancer; inflammation; protein kinase B; toll-like receptor 4


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