Chronic constipation is a highly prevalent condition that poses a risk to human health. Some individuals suffer from intractable functional constipation (IFC), which is recurrent and insensitive to traditional treatments, and may eventually require colectomy to relieve symptoms. IFC is a challenging condition to cure worldwide as its etiology remains unknown.
Dr. Zhu and Chen proposed that specific pathogen colonization maybe induce the occurrence of IFC. To verify their idea, they screened gut microbiota in intestinal mucosa with IFC and isolated the pathogen (Shigella sp. PIB.), which could colonize colonic mucosa, produce docosapentaenoic acid (DPA) and inhibit intestinal motility. Oral administration of PIB induced constipation symptoms in C57BL/6L mice, evidenced by delayed gut transit time, lower fecal water content, and slower colonic peristalsis contraction. The pathogenesis was listed in Figure 1.
Figure 1. PIB enters into organism from mouth, colonizes in mucosa, produces DPA and inhibits colonic contraction.
It’s hard to detect pathogen of IFC from over 1012 gut microbiota. With whole genome sequence, bioinformatic analysis and wet experiments, they established a sensitive and specific PCR method to find PIB from human stool. In addition, they also found DPA test from stool with HPLC to predict IFC. About 75% IFC sufferers exhibited PIB positive or higher DPA level, while none in healthy or non-IFC patients. The results suggest these methods are ideal diagnostic approach to find IFC.
PIB was insensitive to most antibiotics, so it’s impossible to use antibiotics to cure IFC. Dr. Zhu’s team screened phages from environment sample, which specifically killed PIB in vitro and in vivo. Furthermore, oral administration of these phages could reverse gut motility deficiency in PIB+ mice and improve constipation phenotype (Figure 2). Therefore, phage maybe useful to clinical IFC treatment.
Figure 2. The phages killed PIB totally.
The study was published in the Journal of Clinical Investigation on May 26, 2022. Chen Xin, Qiu Tiantian and Wang Yeare co-first authors of the paper. Zhu Minsheng, Jiang Jun and Zhang Xuena are co-corresponding authors. The teams of Chen Yuanxin (Shaanxi An-Ning-Yunsheng Biotechnology Limited Company), Chen Huaqun (Nanjing Normal University) and Zhang Jian (Yunnan University) also contribute to the work.
Link to the paper: https://www.jci.org/articles/view/150097
