Autotaxin (ATX) inhibits autophagy leading to exaggerated disruption of intestinal epithelial barrier in colitis.

Inflammatory bowel disease (IBD) is an immune-mediated disease. Autotaxin (ATX) is associated with increased inflammatory molecules, however, its effect on IBD is not well understood. Autophagy plays an important role in IBD, whether ATX and autophagy act in concert in IBD remains unknown. This study is to explore the possible mechanisms of ATX affecting autophagy leading to the disruption of intestinal epithelial barrier, thereby exacerbating colitis. The expression of ATX was upregulated in UC patients and dextran sulfate sodium (DSS)-induced colitis mice. Here, we described that providing an ATX inhibitor during DSS colitis increased autophagy and ameliorated colonic inflammation. Conversely, intrarectal administration with recombinant (r)ATX increased colitis and decreased autophagy. This pro-colitic effect was attenuated in mice treated with rapamycin, resulting in increased autophagy activity and mild colitis. Moreover, the inhibitory effect of rATX on autophagy was confirmed in vitro and was reversed by the addition of rapamycin. The damaging effects of ATX on epithelial barrier function were reversed by ATX inhibitor or rapamycin treatment. In sum, our results show that ATX can inhibit autophagy through the mTOR pathway, resulting in exaggerated damage to the intestinal epithelial barrier during colitis. These findings suggest that ATX may be a key pro-colitic factor, and represent a potential therapeutic target for treating IBD in the future.

[Effect of flooding time on community structure and abundance of Geobacteraceae in paddy soil].

OBJECTIVE: The dynamic characteristics of community structure and relative abundance of Geobacteraceae were investigated to understand their response to microbial iron (III) reducing in flooded paddy soil. METHODS: The paddy soil was incubated anaerobically and the amount of Fe(II) was determined during the flooding incubation. We retrieved Geobacteraceae sequences from clone libraries constructed for different time points (1 h and day 1, 5, 10, 20 and 30) after flooding of the paddy soil. The diversity and community structure were analyzed by using RFLP method, and the relative abundance of Geobacteraceae was detected by real-time PCR. RESULTS: Microbial reduction of iron (III) changed greatly in early time and was stable after incubated for 20 d in paddy soil. The largest iron reduction potential was 10.16 mg/g with a Vmax of 1.064 mg/(g x d) at the time of 4.84 d whereas this process achieved plateau after 20 days flooding. Diversity of Geobacteraceae, given by alpha indices, fluctuated during the flooding incubation. Two peaks of diversity were observed in treatments of 5 d and 20 d respectively, while significant low diversity appeared in samples of 10 d and 30 d. Beta indices described the differences between community structures of Geobacteraceae and hence reflected the variation of the flooding situation over time. In all samples, 10 RFLP-based preponderant types were found, which fell into clade 1 and clade 2 of Geobacteraceae. The relative abundance of Geobacteraceae was the lowest in 1 d (1.20% ) and the highest in 20 d (4.54%). CONCLUSION: The dynamic variation of Geobacteraceae diversity, community structure and abundance are closely related to microbial iron (III) reducing in flooding paddy soil.