Yangyang Liu

Endoscopic papillary balloon dilatation versus endoscopic sphincterotomy in the treatment for choledocholithiasis: A meta-analysis

Background and Aim:  Endoscopic papillary balloon dilatation (EPBD) and endoscopic sphincterotomy (EST) are two common nonsurgical treatments endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis. The aim of this study was to compare the efficacy and safety of EPBD and EST in the treatment for choledocholithiasis, confining the analysis to work reported in the last decade.

Endoscopic sphincterotomy plus balloon dilation versus endoscopic sphincterotomy for choledocholithiasis: A meta-analysis.

Endoscopic sphincterotomy (EST) alone and EST combined with balloon dilation (ESBD) are important endoscopic techniques for stone extraction. We were to conduct a meta‐analysis to compare the efficacy and safety of ESBD and EST.

Water intubation method can reduce patients' pain and sedation rate in colonoscopy: a meta-analysis.

Several randomized controlled trials (RCT) have shown that water infusion in lieu of air insufflation reduces sedation rate and pain score and increases cecal intubation rate in colonoscopy. The aim of the present study was to confirm the beneficial effects of the water intubation method over the air method. Electronic databases were searched to identify RCT reporting colonoscopy detection using the water method. The pooled data of sedation rate, pain score and other procedure‐related outcomes were analyzed. Then, 15 full‐text articles were selected and assessed. Nine trials with high‐quality scores were enrolled into this meta‐analysis including a total of 1414 participants. Pooled odds ratio (OR) of sedation rate was 0.392 (95% confidence interval (CI): 0.288–0.533, P = 0.000). Pooled weighted mean difference (WMD) of pain score was −1.543 (95% CI: −2.107–−1.069,P = 0.000). Pooled OR of cecal intubation rate was 1.90 (95% CI: 1.29–2.82, P = 0.001). Pooled OR of polyp detection rate and adenoma detection rate were 0.805 (95% CI: 0.606–1.069, P = 0.134) and 0.913 (95% CI: 0.681–1.223, P = 0.168), respectively. Pooled WMD of cecal intubation time was 0.701 (95% CI: −0.486–1.889, P = 0.247). This meta‐analysis confirmed that the water method significantly reduced sedation rate and degree of pain without decreasing cecal intubation rate and disease detection rate and without requiring more cecal intubation time, suggesting that the novel water method is better than the conventional air method in colonoscopy detection.

A novel strain of Bacteroides fragilis enhances phagocytosis and polarises M1 macrophages

Commensal Bacteroides fragilis possesses immune-regulatory characteristics. Consequently, it has been proposed as a potential novel probiotic because of its therapeutic effects on immune imbalance, mental disorders and inflammatory diseases. Macrophages play a central role in the immune response, developing either a classical-M1 or an alternative-M2 phenotype after stimulation with various signals. The interactions between macrophages and B. fragilis, however, remain to be defined. Here, a new isolate of B. fragilis, ZY-312, was shown to possess admirable properties, including tolerance to simulated gastric fluid, intestinal fluid and ox bile, and good safety (MOI = 100, 200) and adherent ability (MOI = 100) to LoVo cells. Isolate ZY-312 cell lysate promoted phagocytosis of fluorescent microspheres and pathogenic bacteria in bone marrow-derived macrophage (BMDM) cells. Gene expression of IL-12, iNOS and IL-1β in BMDM cells was increased after treatment with ZY-312, indicating the induction of M1 macrophages, consistent with enhanced secretion of NO. Cell surface expression of CD80 and CD86 was also increased. This study is the first to demonstrate that B. fragilis enhances the phagocytic functions of macrophages, polarising them to an M1 phenotype. Our findings provide insight into the close relationship between B. fragilis and the innate immune system.

Safety Evaluation of a Novel Strain of Bacteroides fragilis

Commensal non-toxigenic Bacteroides fragilis confers powerful health benefits to the host, and has recently been identified as a promising probiotic candidate. We previously isolated B. fragilis strain ZY-312 and identified it as a novel strain based on 16S rRNA sequencing and morphological analyses. We also determined that ZY-312 displayed desirable probiotic properties, including tolerance to simulated digestive fluid, adherence, and in vitro safety. In this study, we aim to investigate whether ZY-312 meets the safety criteria required for probiotic bacteria through comprehensive and systematic evaluation. Consequently, the fatty acid profile, metabolite production, and biochemical activity of strain ZY-312 were found to closely resemble descriptions of B. fragilis in Bergey’s manual. Taxonomic identification of strain ZY-312 based on whole genome sequencing indicated that ZY-312 and ATCC 25285 showed 99.99% similarity. The 33 putative virulence-associated factors identified in ZY-312 mainly encoded structural proteins and proteins with physiological activity, while the lack of bft indicated that ZY-312 was non-toxigenic. In vivo safety was proven in both normal and immune-deficient mice. The 11 identified antibiotic resistance genes were located on the chromosome rather than on a plasmid, ruling out the risk of plasmid-mediated transfer of antibiotic resistance. In vitro, ZY-312 showed resistance to cefepime, kanamycin, and streptomycin. Finally, and notably, ZY-312 exhibited high genetic stability after 100 passages in vitro. This study supplements the foundation work on the safety evaluation of ZY-312, and contributes to the development of the first probiotic representative from the dominant Bacteroidetes phylum.

Bioluminescence Imaging to Track Bacteroides fragilis Inhibition of Vibrio parahaemolyticus Infection in Mice

Bacteroides fragilis is an anaerobic, Gram-negative, commensal bacterium of the human gut. It plays an important role in promoting the maturation of the immune system, as well as suppressing abnormal inflammation. Many recent studies have focused on the relationship between B. fragilis and human immunity, and indicate that B. fragilis has many useful probiotic effects. As inhibition of intestinal pathogens is an important characteristic of probiotic strains, this study examined whether B. fragilis could inhibit pathogenic bacteria. Results showed that Vibrio parahaemolyticus was inhibited by B. fragilis in vitro, and that B. fragilis could protect both RAW 264.7 and LoVo cells from damage caused by V. parahaemolyticus. Using in vivo imaging, we constructed a light-emitting V. parahaemolyticus strain and showed that B. fragilis might shorten the colonization time and reduce the number of lux-expressing bacteria in a mouse model. These results provide useful information for developing B. fragilis into a probiotic product, and also indicate that this commensal bacterium might aid in the clinical treatment of gastroenteritis caused by V. parahaemolyticus.

Bacteroides fragilis Protects Against Antibiotic-Associated Diarrhea in Rats by Modulating Intestinal Defenses

Antibiotic-associated diarrhea (AAD) is iatrogenic diarrhea characterized by disruption of the gut microbiota. Probiotics are routinely used to treat AAD in clinical practice; however, the effectiveness and mechanisms by which probiotics alleviate symptoms remain poorly understood. We previously isolated a non-toxic Bacteroides fragilis strain ZY-312, which has been verified to be beneficial in certain infection disorders. However, the precise role of this commensal bacterium in AAD is unknown. In this study, we successfully established an AAD rat model by exposing rats to appropriate antibiotics. These rats developed diarrhea symptoms and showed alterations in their intestinal microbiota, including overgrowth of some pathogenic bacteria. In addition, gastrointestinal barrier defects, indicated by compromised aquaporin expression, aberrant tight junction proteins, and decreased abundance of mucus-filled goblet cells, were also detected in ADD rats compared with control animals. Of note, oral treatment with B. fragilis strain ZY-312 ameliorated AAD-related diarrhea symptoms by increasing the abundance of specific commensal microbiota. Interestingly, we demonstrated that these changes were coincident with the restoration of intestinal barrier function and enterocyte regeneration in AAD rats. In summary, we identified a potential probiotic therapeutic strategy for AAD and identified the vital roles of B. fragilis strain ZY-312 in modulating the colonic bacterial community and participating in microbiota-mediated epithelial cell proliferation and differentiation.

In vivo Imaging of a Novel Strain of Bacteroides fragilis via Metabolic Labeling

Non-toxigenic Bacteroides fragilis is regarded as a potential candidate for probiotic owing to its various advantages. We previously isolated a new strain of B. fragilis (ZY-312) and verified its biosafety and capability of inhibiting the growth of pathogens in vivo. However, the colonization of ZY-312 in gastrointestinal (GI) tract remains to be determined. To track the colonization of ZY-312, mice were gavaged with ZY-312 labeled by means of metabolic oligosaccharide engineering and bioorthogonal click chemistry or given AF647-dibenzocyclooctyne (DIBO) directly. Then the fluorescence was detected in GI tract, spleen and kidneys. Results showed that ZY-312 could be labeled by metabolic oligosaccharide engineering, and the optimal incubation time with AF647-DIBO was 5 h in vitro. Following oral gavage with AF647-DIBO labeled ZY-312 or AF647-DIBO alone, mice were subjected to in vivo imaging and the fluorescence intensity was similar in both groups 3 h, 6 h, and 12 h post the gavage. The fluorescence of AF647-DIBO group disappeared 24 h post gavage which was probably due to the excretion via GI tract. While the fluorescence of AF647-DIBO labeled ZY-312 retained in the cecum for as long as 48 h. Immunofluorescence assay further confirmed that labeled ZY-312 transiently colonized not only in cecum but also in stomach, ileum and colon of mice 48 h post-gavage and that no massive accumulation of ZY-312 was detected in other organs such as kidneys and spleen. In conclusion, ZY-312 could transiently colonize in GI tract, mainly in cecum, for at least 48 h, and it hardly disseminate to other organs, which shed new light on the future development of B. fragilis as a probiotic product.

Endoscopic large balloon dilation versus endoscopic sphincterotomy in patients with choledocholithiasis

We read with interest the article by Feng et al. [1] entitled ‘‘Comparison of endoscopic papillary large balloon dilation and endoscopic sphincterotomy for retrieval of choledocholithiasis: a meta-analysis of randomized controlled trials’’, which discussed the efficacy and safety of endoscopic large balloon dilation (EPLBD) and endoscopic sphincterotomy (EST) for the treatment of choledocholithiasis. The authors tried to do a systematic review and metaanalysis of the ‘‘randomized controlled trials (RCT)’’ from several databases, two of which are actually retrospective studies [2, 3]. EST has been a standard endoscopic treatment for the removal of common bile duct (CBD) stones, but it is inclined to cause pancreatitis, bleeding, and perforation. Recently, EPLBD has been advocated as an alternative to EST for the management of CBD stones, though it may have a higher risk of post-ERCP pancreatitis (PEP). It remains controversial whether EPLBD is comparable to EST with regard to the feasibility and safety for the management of CBD stones, especially large or difficult stones. In this review, the authors demonstrated that EPLBD was equivalent to EST for the removal of large stones. However, among the seven included studies, only one compared EPLBD and EST, and the other six compared endoscopic balloon dilation following EST (ESLBD) and EST, which is another serious issue. The combination of these two kinds of studies is not recommended by the Cochrane handbook, because it will cause unknown biases by combining ‘‘apples’’ with ‘‘oranges’’ [4]. Furthermore, ESLBD is a different endoscopic treatment for choledocholithiasis, which can combine the merits of EPLBD and EST. Therefore, it is inappropriate to draw the conclusion by summarizing the results from studies comparing ESLBD versus EST and EPLBD versus EST. Endoscopic mechanical lithotripsy (EML) will be needed as a remedy when stones fail to be removed, a problem which has been found to be reduced in the EPLBD group. However, the enrolled study by Stefanidis [5] applied EML to all the patients of the EST group but none of the EPLBD group, which will probably increase the overall usage of EML in the EST group. Post-ERCP hemorrhage is another serious complication after sphincterotomy or balloon dilation, the risk of which was found to be lower in the EPLBD group. However, nine patients with uncorrected coagulopathy were enrolled in the study by Garcia-Cano [3] and thus it should be excluded from Feng’s study, or sensitivity analysis should be done to explore whether it was biased and able to be included in the meta-analysis.