Symposium

Symposium 3 Crosstalk of the microbiome and the host: Forefront of gut microbiota researchs and the prospect in psychiatry field シンポジウム3 菌叢と宿主のクロストーク：腸内細菌研究の最前線と、精神科領域における今後の展望

SY3-1 Up to date of the treatment strategy for symbiosis with the gut microbiota 腸内細菌叢との共生を目指した治療戦略up to date Mizuno Shinta（水野慎大） Division of Gastroenterology and Hepatology, Keio Univ., Tokyo, Japan Metagenomics enabled the analysis of intestinal microbiota without bacteriological culture. The Human Microbiome Project revealed that the human microbiome comprised about 10¹⁴ bacteria, the same as the total cell number of human body. It has become clear that intestinal microbiota plays an important role not only in metabolism but also in defense against infection and differentiation of host immune cells. Systemic diseases in addition to gastrointestinal disorders are associated with dysbiosis.Among the treatment strategies for restoration of the intestinal microbiota, the most widely used method is probiotics, but only one type was shown to be effective for the patients with inflammatory bowel disease. One factor is that the number of bacteria administered is too small compared to the whole intestinal bacterial flora. To solve this problem, fecal microbiota transplantation (FMT) was developed. In clinical studies of FMT for recurrent Clostridium difficile infection (CDI), FMT treated group was overwhelmingly inhibited in relapse compared with antimicrobial therapy. We are also conducting clinical research on FMT for rCDI, ulcerative colitis, functional gastrointestinal disorders (FGID). Although efficacy against ulcerative colitis was not confirmed, effective cases were confirmed for rCDI and FGID. Searching for adaptive diseases of FMT is being pursued and protocols including the frequency and method of administration are being studied. Although no serious adverse event associated with FMT have been reported so far, problems such as transmission of unknown infectious diseases, complications of the whole work and invasion to patients remain. Continuous efforts are required to ensure that treatment strategies based on human wisdom develop as preemptive therapy.		SY3-2 Role of gut microbiota in the pathophysiology of anorexia nervosa 神経性やせ症の病態形成における腸内細菌叢の役割 Hata Tomokazu（波夛伴和），須藤信行 Dept. of Psychosom. Med., Kyushu Univ. It is becoming clear that gut microbiota can play an important role in the regulation of weight gain and host adiposity. In anorexia nervosa (AN) patients, the energy requirement for body-weight gain is higher than would be expected because of the cost of energy storage. Factors such as increased physical activity or diet-induced thermogenesis are potentially involved in the poor weight gain response; however, the precise mechanism explaining this discrepancy remains to be clarified. We hypothesized that gut microbes might contribute to some of the major features such as poor weight gain and mental disturbances in AN patients. Indeed, gut microbes from AN patients were reportedly different from those of control subjects (PLoS ONE 10(12):e0145274). To further clarify the contribution of gut dysbiosis to AN pathologies, we established gnotobiotic mice that were transplanted with gut microbes derived from AN patients, and are now investigating body weight gain and behavioral characteristics using these mice. In this symposium, based on a series of our research data, I’d like to talk about possible role of gut microbiota in AN pathophysiology.

SY3-3 Gut microbiota and depression 腸内細菌とうつ病 Sanada Kenji（真田建史） Department of Psychiatry, Showa University School of Medicine, Tokyo, Japan Gut is called as the “second brain”. Recently the impact of the microbiota on neural development has garnered attention and the technology of metagenomics has developed exhaustively analyzing genetics on the gut microbiota. However, a few clinical studies have been conducted to investigate the association between the gut microbiota and depression. Some of them showed that patients with depression had distinct microbiota profile compared to healthy controls. In Japan, only one study demonstrated a significant difference in two bacterial counts in the gut in patients with depression compared to healthy subjects. Thus, further research is warranted to examine microbiota profiles in depression. To this aim, we conducted a systematic computerized literature search of MEDLINE, PubMed, EMBASE, PsycINFO and Cochrane library. The reference lists of the identified original articles and reviews were also searched manually for additional studies. The search identified 95 records, of which 12 full-text articles. Of these, we selected nine studies that examined the characteristics of gut microbiota in patients with depression: six are cross sectional studies and three are conducted with an intervention. I will summarize the current status in the field by using this systematic review.		SY3-4 Intestinal microbiota and Autism Spectrum Disorder 腸内細菌と自閉症スペクトラム障害 Kurokawa Shunya（黒川駿哉）¹，岸本泰士郎¹，工藤駿¹，石井大喜²，真田建史³，福田真嗣⁴，三村將¹ ¹Department of Psychiatry, Keio University School of Medicine, Tokyo, Japan ²Faculty of Pharmacy, Keio University, Tokyo, Japan ³Showa University Karasuyama Hospital, Tokyo, Japan ⁴Institute for Advanced Biosciences, Keio University, Yamagata, Japan Gastrointestinal(GI) symptoms such as constipation and diarrhea are highly associated with ASD (Autism Spectrum Disorder), and there is a correlation between severity of GI symptoms and ASD related symptoms with observed disturbance of the intestinal microbiota (Dysbiosis). Treatment with probiotics and FMT (Fecal Microbiota Transplantation) to restore the intestinal environment may be effective to the core symptoms of ASD. However, its mechanism is unclear, and information about the preferable combinations of bacterial species and its metabolites is poor. Moreover, data of Japanese population who differ in race and food culture are overwhelmingly short.Here we will shortly report a case of a child with ASD who dramatically improved her communication and social interaction by the administration of probiotics. Next, we will perform selective reviews of the research being conducted in this field. Finally, we will introduce our observational study targeting children with ASD, ADHD, their siblings, and typically developed children in Japan. Our method combining metagenomic analysis and metabolome analysis of the microbiota (Metabolo-genomics) with detailed clinical evaluation, may give us information to elucidate the unknown pathophysiology of ASD and the related microbiota. There is a possibility that a new diagnosis centering on the intestinal microbiota, and a new individualized therapy targeting individual intestinal microbiota may be developed in the near future.