Fig. 3

Colonization of germ free mice with microbiota obtained from feral mice protects against viral infection and inflammation-induced cancer. Pregnant, germ free C57BL/6 mice were colonized via oral gavage of gut microbiota obtained from feral mice (WildR mice) or from SPF C57BL/6 mice (LabR mice). Barrier-housed C57BL/6 mice (Lab mice) were used as controls to compare to WildR and LabR mice. a Male and female mice in all three groups of mice were infected (intranasally) with influenza A virus (IAV; Puerto Rico/8/1934 H1N1 strain). Approximately 92% of the WildR mice infected with IAV survived for 18 days post-infection whereas only 17% of the LabR and Lab mice were alive at 18 days post-infection. b Survival of WildR mice was associated with ∼10-fold lower titers of lung-residing IAV as well as significantly lower lung histopathology scores and inflammatory cytokine levels when compared with LabR and Lab mice. c Inflammation-induced colorectal cancer was induced in all three groups of mice via a single injection (i.p.) of the mutagen azoxymethane (10 mg/kg of body weight) followed by induction of colonic inflammation via oral (ab libitum) administration of dextran sodium sulfate (2–2.5%) in the drinking water. Representative images of dissected colons demonstrated greater numbers of colonic tumors (tumors indicated by red dots) in Lab and LabR mice when compared with WildR mice. d Top Panel: Representative histopathology (10x magnification) of H&E-stained sections of longitudinal colon tumors with arrows indicating well-differentiated adenocarcinoma in the mucosa. Histopathological analyses revealed that Lab and LabR developed tubular adenoma, well-differentiated tubular adenocarcinoma and mucinous carcinoma. Furthermore, mucinous carcinoma cells were found invading the submucosa and muscular layer where moderate-severe inflammation was also noted. Asterisks identify mucinous nodules. In contrast, WildR mice developed smaller numbers of colonic tumors, reduced tumor area/colon area, diminished tumor invasion and less inflammation when compared with the LabR and Lab mice that received the same treatment protocol. Bottom Panel: Movat’s staining of serial sections from the same tumors presented in the top panels clearly shows the presence of mucinous nodules (mucin stains green) containing mucinous carcinoma cells in submucosa and muscle layers of Lab and LabR but not WildR tumors. Reproduced from [15] with permission