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Gut microbes play a crucial role in the development of colorectal cancer. Chitooligosaccharides (COS), are oligomer that are depolymerized from chitosan and possess a wide range of biological activities. In this study, the effects of COS on colorectal cancer (CRC) development were evaluated using azoxymethane and dextran sulfate sodium (AOM/DSS) induced mouse model of CRC (CACM). In the COS-treated CRC group (CMCOS), COS protected mice from CRC by decreasing the disease activity index, tumor incidences and multiplicity, and the mRNA levels of COX-2, IL-6, TNF-α, IL-1β, IL-10, and IKK-β mRNA in colonic epithelial cells. The results of a cage-exchanged experiment, in which mice from the CACMe and CMCOSe treatments exchanged cages every day to interact with microbes, showed that gut microbes play an important role in preventing CAC by COS. The abundances of fecal bacteria (total bacteria, Lactobacillus, Enterococcus, Fusobacterium nucleatum and butyrate-producing bacteria) were detected by qPCR on the 0th, 1st, 3rd, 6th, 9th, and 10th weekends. Furthermore, microbiota and mycobiota were analyzed by high-throughput sequencing on an Illumina MiSeq PE300 system. COS protected mice from CRC by reversing the imbalance of bacteria and fungi, especially by reducing the abundance of Escherichia–Shigella, Enterococcus, and Turicibacter, and increasing the levels of Akkermansia, butyrate-producing bacteria and Cladosporium.

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The differences between luminal microbiota (LM) and mucosal microbiota (MAM) were little known, especially in duodenum. In this study, LM and MAM in colon and duodenum of mice were investigated through 16S rRNA high-throughput sequencing. The lowest bacterial diversity and evenness were observed in duodenal LM (D_LM), followed by duodenal MAM (D_MAM). Meanwhile, the bacterial diversity and evenness were obviously increased in D_MAM than these in D_LM, while no significant difference was observed between colonic MAM (C_MAM) and colonic LM (C_LM). PCoA analysis also showed that bacterial communities of LM and MAM in duodenum were completely separated, while these in colon overlapped partly. The ratio of Firmicutes to Bacteroidetes (F/B) in D_MAM was significantly higher than that in D_LM. Lactobacillus was largely enriched and was the characteristic bacteria in D_LM. The characteristic bacteria in D_MAM were Turicibacter, Parasutterella, Marvinbryantia and Bifidobacterium, while in C_LM they were Ruminiclostridium_6, Ruminiclostridium_9, Ruminococcaceae_UCG_007 and Lachnospiraceae_UCG_010, and in C_MAM they were Lachnospiraceae_NK4A136, Mucispirillum, Alistipes, Ruminiclostridium and Odoribacter. The networks showed that more interactions existed in colonic microbiota (24 nodes and 74 edges) than in duodenal microbiota (17 nodes and 29 edges). The 16S rDNA function prediction results indicated that bigger differences of function exist between LM and MAM in duodenum than these in colon. In conclusion, microbiota from intestinal luminal content and mucosa were different both in colon and in duodenum, and bacteria in colon interacted with each other much more closely than those in duodenum.

Novel and effective radiosensitizers that can enhance radiosensitivity of tumor tissues and increase the local radiation dose are highly desirable. In this work, templated by bovine serum albumin (BSA), Bi2Se3–MnO2 nanocomposites (Bi2Se3–MnO2@BSA) were fabricated via biomineralization, while Bi2Se3 nanodots act as radiosensitizers to increase the local radiation dosage because of their strong X-ray attenuation ability, and MnO2 with catalase-like activity can increase the oxygen concentration in tumors by triggering the decomposition of tumor endogenous H2O2 so as to improve the hypoxia-associated radioresistance of tumors. Owing to the interaction of the two components in the interface, Bi2Se3–MnO2@BSA showed promoted catalytic activity compared to MnO2@BSA, favoring tumor radiotherapy (RT) sensitization. BSA templating enabled the nanocomposites with high colloidal stability and biocompatibility as well as satisfactory tumor targeting both in vitro and in vivo; thus, an enhanced RT efficacy was obtained. Moreover, the proposed Bi2Se3–MnO2@BSA exhibited excellent performances in computerized tomography and magnetic resonance imaging. Thus, this work provides a tumor microenvironment-responsive multifunctional theranostic nanoagent with an improved performance for imaging-guided tumor RT sensitization.