SCIENTIFIC REPORTS open Helicobacter pylori infection can affect SUBJECT AREAS energy modulating hormones and body MCRoauNoOY weight in germ free mice EXPERIMENTAL MODELS OF DISEASE Yalda Khosravi Shih Wee Seow 2, Arlaine Anne Amoyo?, Kher Hsin Chiow, Tuan Lin Tan, e Yen Wong Qian Hui Poh 3, Ignatius Mario Doli Sentosa Ralph M. Bunte, Sven Pettersson56 7, Received Mun Fai Loke& Jamuna Vadivelu' 16 October 2014 Acce Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia, National Cancer 2 February 2015 Centre, Singapore, Singapore, School of Chemical and Life Sciences, ore Polytechnic, Singapore, Duke-NUS Graduate MedicalSchool, Singapore, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden, Published LKC School of Medicine, Nanyang Technological University, Singapore, Singapore, 'SCELSE Microbiome Centre, Nanyang Helicobacter pylori, is an invariably commensal resident of the gut microbiome associated with gastric ulcer Correspondence and in adults. In addition, these patients also suffered from a low grade inflammation that activates the immune quests for materials system and thus increased shunting of energy to host defense mechanisms. To assess whether a H pylori hould be addressed to infection could affect growth in early life, we determined the expression levels of selected metabolic gut 」V. amuna@ummc hormones in germ free(GF)and specific pathogen-free(SPF)mice with and without the presence of H. Pylori. Despite H. pylori-infected(SPFH) mice display alteration in host metabolism(elevated levels of edu.my) leptin, insulin and peptide YY) compared to non-infected SPF mice, their growth curves remained the same SPFH mice also displayed increased level of eotaxin-1. Interestingly, GF mice infected with H pylori(GFH) also displayed increased levels of ghrelin and PYY. However, in contrast to SPFH mice, GFH showed reduced It gain and malnutrition. These preliminary findings show that exposure to H. pylori alters ost metabolism early in life; but the commensal microbiota in SPF mice can attenuate th th retarding effect from H pylori observed in GF mice. Further investigations of possible additional side effects of H. pylori are highly warranted. he largest human microbiome is the digestive tract, more accurately the large intestine. It harbors approxi mately 100 trillion(10")bacterial cells and more than a 100 times the quantity/number of genes of the human genome!. We acquired the gut microbiota at the time of birth or immediately after birth and its composition depends on many factors, including the genetic background, environment and diet. The micro- biome is usually heterogeneous during the first day of life, and after the first week, a stable bacterial flora will be established, The composition and complexity of the microbiome can be affected by physiological changes, such as aging and pregnancy.. Antibiotic treatment and metabolic, immunological or infectious diseases will also hange the gut microbiota. The gut microbiota plays a significant role in many vital functions, such as energy harvest from the diet and energy storage", development and regulation of the gut-associated mucosal immune stem, regulation of the central nervous system, detoxification of xenobiotics and carcinogens, and protection against colonization by pathogens. Alteration of fecal and intestinal mucosal microbiome may also be a cause of nflammatory bowel disease, obesity and metabolic syndrome. a recent study comparing germ-free(GF)mice bsence of normal gut microbiota) and their specific pathogen free(SPF)counterparts(with normal gut icrobiota)showed that the absence of normal gut microbiota could affect the mices behavior and the expression of genes that regulate motor control and anxiety. Interestingly, in the same study, the authors also demonstrated that GF mice inoculated with normal gut microbiota early in life displayed similar characteristics as SPF mice Thus, they postulated that normal gut microbiota might be responsible for modulating brain development during early stages of life. The ancient gastric pathogen, Helicobacter pylori, is a key member of the human gastric microbiome. It co- evolved with the human race and our association with H pylori could be traced as early back as 60,000 years ago Furthermore, it resides in the stomach of more than half of the global population regardless of ethnicity and geographical region. Many acquired the bacteria during early childhood via intra-familial transmission and SCIENTIFIC REPORTS I 5: 8731 I DO1: 10.1038/ srep08731Helicobacter pylori infection can affect energy modulating hormones and body weight in germ free mice Yalda Khosravi1 , Shih Wee Seow2 , Arlaine Anne Amoyo2 , Kher Hsin Chiow3 , Tuan Lin Tan3 , Whye Yen Wong3 , Qian Hui Poh3 , Ignatius Mario Doli Sentosa3 , Ralph M. Bunte4 , Sven Pettersson5,6,7, Mun Fai Loke1 & Jamuna Vadivelu1 1 Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia, 2 National Cancer Centre, Singapore, Singapore, 3 School of Chemical and Life Sciences, Singapore Polytechnic, Singapore, 4 Duke-NUS Graduate Medical School, Singapore, 5 Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden, 6 LKC School of Medicine, Nanyang Technological University, Singapore, Singapore, 7 SCELSE Microbiome Centre, Nanyang Technological University, Singapore, Singapore. Helicobacter pylori, is an invariably commensal resident of the gut microbiome associated with gastric ulcer in adults. In addition, these patients also suffered from a low grade inflammation that activates the immune system and thus increased shunting of energy to host defense mechanisms. To assess whether a H. pylori infection could affect growth in early life, we determined the expression levels of selected metabolic gut hormones in germ free (GF) and specific pathogen-free (SPF) mice with and without the presence of H. pylori. Despite H. pylori-infected (SPFH) mice display alteration in host metabolism (elevated levels of leptin, insulin and peptide YY) compared to non-infected SPF mice, their growth curves remained the same. SPFH mice also displayed increased level of eotaxin-1. Interestingly, GF mice infected with H. pylori (GFH) also displayed increased levels of ghrelin and PYY. However, in contrast to SPFH mice, GFH showed reduced weight gain and malnutrition. These preliminary findings show that exposure to H. pylori alters host metabolism early in life; but the commensal microbiota in SPF mice can attenuate the growth retarding effect from H. pylori observed in GF mice. Further investigations of possible additional side effects of H. pylori are highly warranted. T he largest human microbiome is the digestive tract, more accurately the large intestine. It harbors approxi￾mately 100 trillion (1014) bacterial cells and more than a 100 times the quantity/number of genes of the human genome1 . We acquired the gut microbiota at the time of birth or immediately after birth and its composition depends on many factors, including the genetic background, environment and diet1,2. The micro￾biome is usually heterogeneous during the first day of life, and after the first week, a stable bacterial flora will be established3 . The composition and complexity of the microbiome can be affected by physiological changes, such as aging and pregnancy3,4. Antibiotic treatment and metabolic, immunological or infectious diseases will also change the gut microbiota5 . The gut microbiota plays a significant role in many vital functions, such as energy harvest from the diet and energy storage4,5, development and regulation of the gut-associated mucosal immune system3 , regulation of the central nervous system6 , detoxification of xenobiotics and carcinogens, and protection against colonization by pathogens7 . Alteration of fecal and intestinal mucosal microbiome may also be a cause of inflammatory bowel disease, obesity and metabolic syndrome. A recent study comparing germ-free (GF) mice (absence of normal gut microbiota) and their specific pathogen free (SPF) counterparts (with normal gut microbiota) showed that the absence of normal gut microbiota could affect the mice’s behavior and the expression of genes that regulate motor control and anxiety8 . Interestingly, in the same study, the authors also demonstrated that GF mice inoculated with normal gut microbiota early in life displayed similar characteristics as SPF mice. Thus, they postulated that normal gut microbiota might be responsible for modulating brain development during early stages of life. The ancient gastric pathogen, Helicobacter pylori, is a key member of the human gastric microbiome. It co￾evolved with the human race and our association with H. pylori could be traced as early back as 60,000 years ago9 . Furthermore, it resides in the stomach of more than half of the global population regardless of ethnicity and geographical region10. Many acquired the bacteria during early childhood via intra-familial transmission and OPEN SUBJECT AREAS: CLINICAL MICROBIOLOGY EXPERIMENTAL MODELS OF DISEASE Received 16 October 2014 Accepted 2 February 2015 Published 4 March 2015 Correspondence and requests for materials should be addressed to J.V. (jamuna@ummc. edu.my) SCIENTIFIC REPORTS | 5 : 8731 | DOI: 10.1038/srep08731 1