Prebiotics provide an exciting new concept in human nutrition and digestive function for which many physiological and health beneficial effects have been claimed [17
]. Our previous studies have also shown that prebiotics and probiotics have the potentials to reduce procarcinogenic markers (aberrant crypt foci, fecal enzymes) and retain the colonic cellular morphology in six weeks of DMH-treated mice [12
]. Thus, the present study was designed with an aim to further study the effects of lactulose and inulin in six weeks DMH-treated mice with special reference to colonic mass, pH, intestinal microbiome and SCFA production.
The increased body mass in mice belonging to either inulin/lactulose groups may be due to improved gut microbiota as evident by increased lactobacilli counts. However, mice belonging to inulin+DMH treated group had decreased body mass in later phase of experiment that may be due to the initiation of colon carcinogenesis induced by DMH, altered biochemical, physiochemical activity and production of short chain fatty acids and corroborates with earlier studies [19
]. These scientists have also observed decrease in body mass of Fisher 344 male rats when administered with different inulin fractions. However, the increased body mass in inulin+DMH treated mice compared with DMH-treated animals corroborates with earlier observations where it has been demonstrated that administration of prebiotics (Synergy1-Beneo) increased the body mass significantly in rats administered with azoxymethane [20
]. The decreased body mass observed in prebiotic inulin group of mice compared with control mice may be due to short chain fatty acids (propionate) produced by colonic fermentation that may have hypolipidemic effect due to decreased lipogenesis, thereby reducing the concentration of plasma Very Low-Density Lipoproteins (VLDL) [22
]. We also observed that supplementation of lactulose has no effect on body mass and is consistent with the earlier observations. [24
It was interesting to observe that supplementation of inulin and lactulose increased the counts of lactic acid bacteria in feces after 2 weeks inspite of DMH treatment but decreased the colonic mass and pH. This may be due to colonization of lactic acid bacteria in colon and their enhanced metabolic activity as both inulin and lactulose are dietary fibres that favors the growth of resident microbiota. These lactic acid bacteria ferment prebiotics resulting in production of short chain fatty acids that in turn decrease the luminal pH and is in accordance with earlier studies [26
]. These researchers have also found that lactate production by lactic acid bacteria decrease the luminal pH. The observed increased colonic mass in DMH-treated mice may probably be due to the DMH which may have led to the formation of Aberrant Crypt Foci (ACF).
In our earlier study also we have found that prior administration of prebiotic inulin was better than lactulose in reducing ACF counts as it is degraded slowly and passes further along the colon before being completely degraded [13
]. Further, it was interesting to note that administration of either prebiotic inulin or lactulose increased the levels of butyric acid in feces that may have inhibited the proliferation of colorectal tumor
cells probably by decreasing the intestinal pH which may have in turn favored the growth of colonic microbiota and this observation is observed by earlier studies where butyrate has been shown to inhibit the proliferation of colorectal tumor cells [29
]. Moreover, butyric acid, decreases the intestinal pH that is beneficial for the colon since high colonic pH has been shown to promote colon cancer
]. Based on the observations of the present study the underlying proposed anticarcinogenic mechanism of inulin was due to its ability to modify the colonic conditions like colonic pH which affected the growth of colonic microbiome leading to enhanced lactobacilli that produces short chain fatty acid (butyrate) by fermentation which in turn inhibited the cell proliferation.
Taken together, the observation of the present study further strengthens our earlier observation of anticarcinogenic
nature of prebiotic which provides a solid practical basis of prebiotic application that helps in reducing and even reversing the colon cancer. As inulin was found to have better anticarcinogenic property than lactulose due to its ability to reach distal colon, produce short chain fatty acid (butyrate) in the colon
that acidify the environment resulting in decreased colonic pH and thus enhancing the growth of lactobacilli
and reducing the levels of procarcinogenic markers i.e. aberrant crypt foci and procarcinogenic fecal enzymes. Thus, it can be said that diet rich in fibres modulates the gut microbiome subsequently affecting the metabolic profile and human health. However, these observations needs to be further correlated with clinical studies.