Shifts in the Fecal Microbiota Associated with Adenomatous Polyps

Abstract

Background Adenomatous polyps are the most common precursor to colorectal cancer (CRC), the second leading cause of cancer death in the United States. We sought to learn more about early events of carcinogenesis by investigating shifts in the gut microbiota of patients with adenomas. Methods We analyzed 16S rRNA gene sequences from the fecal microbiota of patients with adenomas (n=233) and without (n=547). Results Multiple taxa were significantly more abundant in patients with adenomas, including Bilophila, Desulfovibrio, pro-inflammatory bacteria in the genus Mogibacterium, and multiple Bacteroidetes species. Patients without adenomas had greater abundances of Veillonella, Firmicutes (Order Clostridia), and Actinobacteria (family Bifidobacteriales). Our findings were consistent with previously reported shifts in the gut microbiota of CRC patients. Importantly, the altered adenoma profile is predicted to increase primary and secondary bile acid production, as well as starch, sucrose, lipid, and phenylpropanoid metabolism. Conclusions These data hint that increased sugar, protein, and lipid metabolism along with increased bile acid production could promote a colonic environment that supports the growth of bile-tolerant microbes such as Bilophilia and Desulfovibrio. In turn, these microbes may produce genotoxic or inflammatory metabolites such as H2S and secondary bile acids, which could play a role in catalyzing adenoma development and eventually CRC. Impact This study suggests a plausible biological mechanism to explain the links between shifts in the microbiota and CRC. This represents a first step toward resolving the complex interactions that shape the adenoma-carcinoma sequence of CRC and may facilitate personalized therapeutics focused on the microbiota.

Pretreatment with probiotic Bifico ameliorates colitis‐associated cancer in mice: Transcriptome and gut flora profiling

“…As previous studies described, Desulfovibrio had the capacity to degrade sulfate and produce high levels of hydrogen sulfide, which is regarded as a genotoxic agent that might play a role in colitis and colonic tumorigenesis . Desulfovibrio also displays a flourish of relative abundance in IBD colon tissues and in patients with adenoma and rectal cancer . However, most studies have shown that the abundance of Desulfovibrio in the intestinal tract of colon cancer patients does not increase .…”

“…41 Desulfovibrio also displays a flourish of relative abundance in IBD colon tissues and in patients with adenoma and rectal cancer. 14,[42][43][44] However, most studies have shown that the abundance of Desulfovibrio in the intestinal tract of colon cancer patients does not increase. 45,46 Considering its role in triggering colonic inflammation, Desulfovibrio may be of larger significance in CAC initiation and progression than in sporadic colorectal cancer.…”

Synthesis of multi-omic data and community metabolic models reveals insights into the role of hydrogen sulfide in colon cancer

“…Stool DNA extraction [21], quantification, and amplification was performed as described previously [44]. Colon tissue was thawed, weighed, and homogenized prior to DNA extraction.…”

“…Butyrate, a short chain fatty acid (SCFA), is reportedly both an inducer [19] and an inhibitor [20] of CRC tumor development. Hydrogen sulfide, which has been implicated in our work and others’ [12,21–23], is a genotoxic and cytotoxic agent at physiologic concentrations [13,24,25], but it has also been reported as an anti-inflammatory and potentially anti-tumor agent [26–30]. …”

“…In contrast, quantifying the relative abundance of hydrogen sulfide-producing bacteria is far less challenging. Sulfidogenic bacteria such as Bilophila wadsworthia , Fusobacterium species, and sulfur-reducers such as Desulfovibrio species have all been identified within the gut and linked to colon inflammation [32], adenomas [21,33,34], and colon tumors [35–37]. However, these microbial associations are not sufficient for determining microbial metabolite production.…”