Distance burning: how gut microbes promote extraintestinal cancers - PubMed (original) (raw)

Distance burning: how gut microbes promote extraintestinal cancers

Arlin B Rogers. Gut Microbes. 2011 Jan-Feb.

Abstract

Gut microbes play a major role in carcinogenesis of the gastrointestinal tract. We and others have shown in mouse models that colonic bacteria also influence the development of extraintestinal cancers including hepatocellular and mammary carcinomas. Microbes such as Helicobacter hepaticus invoke a proinflammatory microenvironment in the lower bowel that may extend to distant organs, often in the absence of histologically evident inflammation. Innate immunity plays a crucial role in the promotion of liver cancer and other systemic diseases by gut microbes. Additional mechanisms include type 1 adaptive immunity, altered metabolism, and oxidative stress. Emerging links between host genetics, gut microbes, inflammatory bowel disease and colorectal cancer also may prove useful for the correlation of specific bacterial populations with extraintestinal neoplasms. Interruption of deleterious host-microbe networks through judicious use of antibiotics and targeted molecular therapies may help reduce the incidence of liver, breast, and other human cancers.

© 2011 Landes Bioscience

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Figures

Figure 1

Figure 1

Enterically confined H. hepaticus promoted aflatoxin B1-induced liver cancer in mice in association with NFκB activation. (A) Liver histopathology of male (top row) and female (bottom row) mice in the 4 treatment groups; *adenoma, †HCC. (B) Tumor incidence comparison in male and female mice from each treatment group. (C) Adenoma versus carcinoma multiplicity and total tumor surface area comparison in AFB1-exposed males with and without H. hepaticus. (D) Pathways analysis of NFκB-anchored molecular networks altered by H. hepaticus in both the lower bowel and liver. Images reproduced from Fox et al. Gut 2010. {Fox 2010 #4672}.

Figure 1

Figure 1

Enterically confined H. hepaticus promoted aflatoxin B1-induced liver cancer in mice in association with NFκB activation. (A) Liver histopathology of male (top row) and female (bottom row) mice in the 4 treatment groups; *adenoma, †HCC. (B) Tumor incidence comparison in male and female mice from each treatment group. (C) Adenoma versus carcinoma multiplicity and total tumor surface area comparison in AFB1-exposed males with and without H. hepaticus. (D) Pathways analysis of NFκB-anchored molecular networks altered by H. hepaticus in both the lower bowel and liver. Images reproduced from Fox et al. Gut 2010. {Fox 2010 #4672}.

Figure 2

Figure 2

Potential mechanisms of liver tumor promotion by gut microbes. Intestinal bacteria may promote hepatic (and other) distant neoplasms through at least six nonexclusive pathways: (1) altered mucosal permeability with toxin absorption; (2) induction of proinflammatory mucosal/epithelial microenvironments; (3) generalized immune activation; (4) activation of circulating proteases and other serum factors; (5) bacterial nutrient processing and host metabolomics; and (6) disrupted bile and cholesterol/fatty acid homeostasis. APC, antigen-presenting cells; FGFs, fibroblast growth factors; GALT, gut-associated lymphoid tissue; MLN, mesenteric lymph node.

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