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Background Escherichia coli are mostly commensals but also contain pathogenic lineages. It is largely unclear whether the commensal E. coli as the potential origins of pathogenic lineages may consist of monophyletic or polyphyletic populations, elucidation of which is expected to lead to novel insights into the associations of E. coli diversity with human health and diseases. Methods Using genomic sequencing and pulsed field gel electrophoresis (PFGE) techniques, we analyzed E. coli from the intestinal microbiota of three groups of healthy individuals, including preschool children, university students, and seniors of a longevity village, as well as colorectal cancer (CRC) patients, to probe the commensal E. coli populations for their diversity. Results We delineated the 2280 fresh E. coli isolates from 185 subjects into distinct genome types (genotypes) by PFGE. The genomic diversity of the sampled E. coli populations was so high that a given subject may have multiple genotypes of E. coli, with the general diversity within a host going up from preschool children through university students to seniors. Compared to the healthy subjects, the CRC patients had the lowest diversity level among their E. coli isolates. Notably, E. coli isolates from CRC patients could suppress the growth of E. coli bacteria isolated from healthy controls under nutrient-limited culture conditions. Conclusions The coexistence of multiple E. coli lineages in a host may help create and maintain a microbial environment that is beneficial to the host. As such, the low diversity of E. coli bacteria may be associated with unhealthy microenvironment in the intestine and hence facilitate the pathogenesis of diseases such as CRC.

// Yu-Jie Zhou 1, 2 , Dan-Dan Zhao 1, 2 , Huidi Liu 1, 2 , Hao-Ting Chen 1, 2 , Jia-Jing Li 1, 2 , Xiao-Qin Mu 1, 2 , Zheng Liu 3 , Xia Li 1, 2 , Le Tang 1, 2, 6 , Zhan-Yi Zhao 1, 2 , Ji-Heng Wu 1, 2 , Yu-Xuan Cai 1, 2 , Ya-Zhuo Huang 1, 2 , Peng-Ge Wang 1, 2 , Yi-Yue Jia 1, 2 , Pei-Qiang Liang 1, 2 , Xue Peng 1, 2 , Si-Yu Chen 1, 2 , Zhi-Lin Yue 1, 2 , Xin-Yuan Yuan 1, 2, 7 , Tammy Lu 1, 2, 8 , Bing-Qing Yao 1, 2 , Yong-Guo Li 4 , Gui-Rong Liu 1, 2 and Shu-Lin Liu 1, 2, 4, 5 1 Systemomics Center, College of Pharmacy, and Genomics Research Center, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, China 2 HMU-UCFM Centre for Infection and Genomics, Harbin Medical University, Harbin, China 3 Colorectal Surgery Department, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China 4 Department of Infectious Diseases, The First Affiliated Hospital, Harbin Medical University, Harbin, China 5 Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Canada 6 Current affiliation: Department of Ecosystems and Public Health, University of Calgary, Calgary, Canada 7 Current affiliation: Life Sciences, Queen’s University, Kingston, Canada 8 Current affiliation: Biomedical Science, University of Calgary, Calgary, Canada Correspondence to: Shu-Lin Liu, email: slliu@hrbmu.edu.cn Keywords: cancer, malignancy killer, Actinobacteria, gut microbiota, leukemia Received: December 12, 2016 Accepted: April 02, 2017 Published: April 21, 2017 ABSTRACT Cancer as a large group of complex diseases is believed to result from the interactions of numerous genetic and environmental factors but may develop in people without any known genetic or environmental risks, suggesting the existence of other powerful factors to influence the carcinogenesis process. Much attention has been focused recently on particular members of the intestinal microbiota for their potential roles in promoting carcinogenesis. Here we report the identification and characterization of intestinal bacteria that exhibited potent anti-malignancy activities on a broad range of solid cancers and leukemia. We collected fecal specimens from healthy individuals of different age groups (preschool children and university students), inspected their effects on cancer cells, and obtained bacteria with potent anti-malignancy activities. The bacteria mostly belonged to Actinobacteria but also included lineages of other phyla such as Proteobacteria and Firmicutes. In animal cancer models, sterile culture supernatant from the bacteria highly effectively inhibited tumor growth. Remarkably, intra-tumor administration of the bacterial products prevented metastasis and even cleared cancer cells at remote locations from the tumor site. This work demonstrates the prevalent existence of potent malignancy-killers in the human intestinal microbiota, which may routinely clear malignant cells from the body before they form cancers.

Secoisolariciresinol (SECO) is a lignan of potential therapeutic value for diseases such as cancer, but its use has been limited by the lack of ideal production methods, even though its precursors are abundant in plants, such as flaxseeds. Here, we report the characterization of a bacterial strain, S1, isolated from the human intestinal flora, which could produce secoisolariciresinol by biotransformation of precursors in defatted flaxseeds. This bacterium was a Gram-negative and facultatively anaerobic straight rod without capsules. Biochemical assays showed that it was negative for production of oxidase, lysine decarboxylase, ornithine decarboxylase, arginine dihydrolase, and β-glucolase. The G + C content of genomic DNA was 57.37 mol%. Phylogenetic analysis by 16S rRNA and rpoB gene sequences demonstrated S1’s close relatedness to Klebsiella. No homologues were found for wzb or wzc (capsular genes), which may explain why Klebsiella sp. strain S1 does not have the capsule and was isolated from a healthy human individual. Based on the percentages of homologous genes with identical nucleotide sequences between the bacteria in comparison, we found that clear-cut genetic boundaries had been formed between S1 and any other Klebsiella strains compared, dividing them into distinct phylogenetic lineages. This work demonstrates that the intestinal Klebsiella, well known as important opportunistic pathogens prevalent in potentially fatal nosocomial infections, may contain lineages that are particularly beneficial to the human health.

The serum total protein levels of the elderly possibly decrease gradually with aging. However, serum total protein levels are not suitable as a uniform reference standard for the elderly at different ages and genders. Thus, we investigated the total serum protein distribution in different gender and age groups of 11,453 elderly individuals aged ≥60 years and without liver or renal disease from Lianyungang, Jiangsu, China. The total protein levels (TPL) of these individuals exhibited normal distribution (Z = 1.206, P = 0.109), whereas the reference range (95% CI) was 54.1 g/L to 82.3 g/L. TPL was higher in females than in males for those aged between 60 and 75 years, whereas no significant difference was observed for those aged between 80 and 95 years. TPL was negatively correlated with age in males (r = -0.1342, P

Due to their low cytotoxicity, controllable size, and unique architecture, cyclodextrin (CD)-based polyrotaxanes and polypseudorotaxanes have inspired interesting exploitation as novel biomaterials. This review will update the recent progress in the studies on the structures of polyrotaxanes and polypseudorotaxanes based on different CDs and polymers, followed by summarizing their potential applications in life science and biotechnology, such as drug delivery, gene delivery, and tissue engineering. CD-based biodegradable polypseudorotaxane hydrogels could be used as promising injectable drug delivery systems for sustained and controlled drug release. Polyrotaxanes with drug or ligand-conjugated CDs threaded on polymer chain with biodegradable end group could be useful for controlled and multivalent targeting delivery. Cationic polyrotaxanes consisting of multiple oligoethylenimine-grafted CDs threaded on a block copolymer chain were attractive non-viral gene carries due to the strong DNA-binding ability, low cytotoxicity, and high gene transfection efficiency. Cytocleavable end caps were also introduced in the polyrotaxane systems in order to ensure efficient endosomal escape for intracellular trafficking of DNA. Finally, hydrolyzable polyrotaxane hydrogels with cross-linked α-CDs could be a desirable scaffold for cartilage and bone tissue engineering.