Bifidobacterium Strain-Specific Enhances the Efficacy of Cancer Therapeutics in Tumor-Bearing Mice

Colorectal cancer (CRC) is among the leading causes of cancer-related death in the world. The development of CRC is associated with smoking, diet, and microbial exposure. Previous studies have shown that dysbiosis of the gut microbiome affects cancer development, because it leads to inflammation and genotoxicity. Supplementation with specific microbiota induces anti-tumor effects by enhancing of anti-tumor immunity. Here, we observed that supplementation with either of two B. breve strains reduces tumor growth in MC38 colon carcinoma-bearing mice. Interestingly, only one B. breve strain boosted the efficacy of cancer therapeutics, including oxaliplatin and PD-1 blockade. Extensive immune profiling and transcriptomic analysis revealed that the boosting B. breve strain augments lymphocyte-mediated anti-cancer immunity. Our results suggest that supplementation with B. breve strains could potentially be used as a strategy to enhance the efficacy of CRC therapeutics.

Bifidobacterium longum subsp. infantis ATCC 15697 and Goat Milk Oligosaccharides Show Synergism In Vitro as Anti-Infectives against Campylobacter jejuni

Bifidobacteria are known to inhibit, compete with and displace the adhesion of pathogens to human intestinal cells. Previously, we demonstrated that goat milk oligosaccharides (GMO) increased the attachment of Bifidobacterium longum subsp. infantis ATCC 15697 to intestinal cells in vitro. In this study, we aimed to exploit this effect as a mechanism for inhibiting pathogen association with intestinal cells. We examined the synergistic effect of GMO-treated B. infantis on preventing the attachment of a highly invasive strain of Campylobacter jejuni to intestinal HT-29 cells. The combination decreased the adherence of C. jejuni to the HT-29 cells by an average of 42% compared to the control (non-GMO treated B. infantis). Increasing the incubation time of the GMO with the Bifidobacterium strain resulted in the strain metabolizing the GMO, correlating with a subsequent 104% increase in growth over a 24 h period when compared to the control. Metabolite analysis in the 24 h period also revealed increased production of acetate, lactate, formate and ethanol by GMO-treated B. infantis. Statistically significant changes in the GMO profile were also demonstrated over the 24 h period, indicating that the strain was digesting certain structures within the pool such as lactose, lacto-N-neotetraose, lacto-N-neohexaose 3′-sialyllactose, 6′-sialyllactose, sialyllacto-N-neotetraose c and disialyllactose. It may be that early exposure to GMO modulates the adhesion of B. infantis while carbohydrate utilisation becomes more important after the bacteria have transiently colonised the host cells in adequate numbers. This study builds a strong case for the use of synbiotics that incorporate oligosaccharides sourced from goat′s milk and probiotic bifidobacteria in functional foods, particularly considering the growing popularity of formulas based on goat milk.

Potential of Inactivated Bifidobacterium Strain in Attenuating Benzo(A)Pyrene Exposure-Induced Damage in Colon Epithelial Cells In Vitro

Long-term exposure to benzo(a)pyrene (BaP) poses a serious genotoxic threat to human beings. This in vitro study investigated the potential of inactivated Bifidobacterium animalis subsp. lactis BI-04 in alleviating the damage caused by BaP in colon epithelial cells. A concentration of BaP higher than 50 μM strongly inhibited the growth of colon epithelial cells. The colon epithelial cells were treated with 50 μM BaP in the presence or absence of inactivated strain BI-04 (~5 × 108 CFU/mL). The BaP-induced apoptosis of the colon epithelial cells was retarded in the presence of B. lactis BI-04 through activation of the PI3K/ AKT signaling pathway, and p53 gene expression was decreased. The presence of the BI-04 strain reduced the intracellular oxidative stress and DNA damage incurred in the colon epithelial cells by BaP treatment due to the enhanced expression of antioxidant enzymes and metabolism-related enzymes (CYP1A1). The data from comet assay, qRT-PCR, and western blot analysis showed that the cytotoxic effects of BaP on colon epithelial cells were largely alleviated because the bifidobacterial strain could bind to this carcinogenic compound. The in vitro study highlights that the consumption of commercial probiotic strain BI-04 might be a promising strategy to mitigate BaP cytotoxicity.

Sequencing analysis and characterization of the plasmid pBIF10 isolated from Bifidobacterium longum

A resident plasmid, pBIF10, was isolated from Bifidobacterium longum B200304, and the full-length sequence of pBIF10 was analyzed. In this sequence, we identified at least 17 major open reading frames longer than 200 bp. A tetracycline resistance gene, tetQ, was identified and verified to confer antibiotic resistance to tetracycline. The plasmid replicon with replication protein B gene (repB) and a typical iteron was identified in pBIF10. An artificial clone vector was constructed with the replicon of pBIF10; the results showed that repB controlled plasmid replication in other bifidobacteria host cells at low transformation frequency. Taken together, the analysis and characterization of pBIF10 provided necessary information for the understanding of antibiotic resistance mediated by a plasmid in a Bifidobacterium strain. GC% and repB sequence analyses indicated that pBIF10 was a molecular hybrid of at least 2 other bacterial genera plasmids.