A risk estimation method for depression based on the dysbiosis of intestinal microbiota in Japanese patients.

Introduction: Early detection of depression is important for preventing depression-related suicides and reducing the risk of recurrence. This study explored the association between depression and intestinal microbiota and developed a depression risk-estimation method based on this. Methods: The intestinal microbiota of Japanese patients with depression (33 males and 35 females) and disease-free controls (246 males and 384 females) in their 20's to 60's were compared by sex using 16S rRNA gene amplicon sequencing. A depression-risk estimation method was developed using structural equation modeling. Results: Intestinal bacteria taxa that differed between depression and control groups were identified based on effect size (absolute value greater than 0.2). Neglecta was more abundant, while Coprobacter, Butyricimonas, Clostridium_XlVb, and Romboutsia were less abundant in the male depression group compared to the male control group. In the female depression group, Massilimicrobiota, Merdimonas, and Sellimonas were more abundant, whereas Dorea and Agathobacter were less abundant compared to the female control group. Several of the intestinal bacterial taxa that were less abundant in depression were associated with butyrate or hydrogen production. Using these depression-associated intestinal bacteria as indicators, risk-estimation models using structural equation modeling for depression were developed. In the risk-estimation models for males and females, the areas under the receiver operating characteristic curve were 0.72 and 0.70, respectively, indicating that these models can distinguish between individuals with and without depression. Conclusions: This study provides insights into depression etiology and aids in its early detection and treatment.

Characteristics of Intestinal Microbiota in Japanese Patients with Mild Cognitive Impairment and a Risk-Estimating Method for the Disorder.

Intestinal microbiota may play a significant role in the development and progression of mild cognitive impairment (MCI). In addition, sex differences in the prevalence of MCI and intestinal microbiota are likely to exist. Therefore, this study investigated the association between MCI and intestinal microbiota by comparing Japanese patients in their 70s with MCI (11 males and 18 females) and disease-free controls (17 males and 23 females), taking sex into account. In both sexes, Clostridium_XVIII, Eggerthella, Erysipelatoclostridium, Flavonifractor, and Ruminococcus 2 were the more abundant taxa in the MCI group, whereas Megasphaera, Oscillibacter, Prevotella, Roseburia, and Victivallis were less abundant. Based on these characteristics, it was hypothesized that the composition of the intestinal microbiota in the MCI group leads to dysregulation of the intestinal microbiota, increased intestinal and blood-brain barrier permeability, and increased chronic neuroinflammation, with the long-term persistence of these abnormalities ultimately leading to cognitive decline. Furthermore, risk estimation models for MCI based on intestinal microbiota data were developed using structural equation modeling. These tests discriminated between the MCI and control groups. Incorporating these factors into intestinal microbiota testing using stool samples may be an efficient method to screen individuals with MCI.

Sex Differences in Intestinal Microbiota and Their Association with Some Diseases in a Japanese Population Observed by Analysis Using a Large Dataset.

In recent years, many studies have focused on the relationship between intestinal microbiota and human health, but the impact of sex has not yet been sufficiently investigated. In this study, sex differences in the intestinal microbiota of a Japanese population were investigated by age group, using a large dataset constructed for a cross-sectional study. α-diversity analysis indicated that the impact of sex differences varied among the 20s-50s age groups but tended to be smaller among the 60s-70s age groups. Fusobacterium, Megamonas, Megasphaera, Prevotella, and Sutterella were more common among males, whereas Alistipes, Bacteroides, Bifidobacterium, Odoribacter, and Ruthenibacterium were common among females. Next, intestinal bacteria potentially associated with 12 diseases were investigated for each sex. The results indicate that many of these differ between males and females, and among age groups. Thus, sex and age should be considered for studies on intestinal microbiota and disease association, prevention, and treatment approaches that target them.

Method for estimating disease risk from microbiome data using structural equation modeling.

The relationship between the human gut microbiota and disease is of increasing scientific interest. Previous investigations have focused on the differences in intestinal bacterial abundance between control and affected groups to identify disease biomarkers. However, different types of intestinal bacteria may have interacting effects and thus be considered biomarker complexes for disease. To investigate this, we aimed to identify a new kind of biomarker for atopic dermatitis using structural equation modeling (SEM). The biomarkers identified were latent variables, which are complex and derived from the abundance data for bacterial marker candidates. Groups of females and males classified as healthy participants [normal control (NC) (female: 321 participants, male: 99 participants)], and patients afflicted with atopic dermatitis only [AS (female: 45 participants, male: 13 participants)], with atopic dermatitis and other diseases [AM (female: 75 participants, male: 34 participants)], and with other diseases but without atopic dermatitis [OD (female: 1,669 participants, male: 866 participants)] were used in this investigation. The candidate bacterial markers were identified by comparing the intestinal microbial community compositions between the NC and AS groups. In females, two latent variables (lv) were identified; for lv1, the associated components (bacterial genera) were Alistipes, Butyricimonas, and Coprobacter, while for lv2, the associated components were Agathobacter, Fusicatenibacter, and Streptococcus. There was a significant difference in the lv2 scores between the groups with atopic dermatitis (AS, AM) and those without (NC, OD), and the genera identified for lv2 are associated with the suppression of inflammatory responses in the body. A logistic regression model to estimate the probability of atopic dermatitis morbidity with lv2 as an explanatory variable had an area under the curve (AUC) score of 0.66 when assessed using receiver operating characteristic (ROC) analysis, and this was higher than that using other logistic regression models. The results indicate that the latent variables, especially lv2, could represent the effects of atopic dermatitis on the intestinal microbiome in females. The latent variables in the SEM could thus be utilized as a new type of biomarker. The advantages identified for the SEM are as follows: (1) it enables the extraction of more sophisticated information when compared with models focused on individual bacteria and (2) it can improve the accuracy of the latent variables used as biomarkers, as the SEM can be expanded.

Characteristics of the Gut Microbiota in Japanese Patients with Premenstrual Syndrome.

Purpose: The present study aimed to characterize the gut microbiota of individuals with premenstrual syndrome. Patients and Methods: The gut microbiota of 24 Japanese women with PMS (PMS group) and 144 healthy Japanese women (control group) were compared. Analysis of the α- and ß-diversities and the gut microbial composition at the genus level were performed using 16S rRNA gene sequence data obtained from stool samples. Results: A significant difference in age was observed between the PMS and control groups; however, no significant difference was observed in BMI. The α-diversity measured using the Simpson index was significantly higher in the PMS group than the control group. Visualization of the ß-diversity using non-metric multidimensional scaling and permutational multivariate analysis of variance (PERMANOVA) showed that the distance of the gut microbiota between the PMS and control groups is significantly different. Furthermore, a significant difference in the composition of the gut microbiota was observed between the PMS and control groups. At the genus level, the abundances of Collinsella, Bifidobacterium, and Blautia were significantly higher in the PMS group than in the control group. In particular, the abundance of Collinsella in the PMS group was approximately 4.5 times higher than that in the control group. To rule out the confounding effect of age in the abundances of Bifidobacterium, Blautia, and Collinsella, the gut microbiota of the PMS and control groups were compared by age group. Results showed that Collinsella had the highest effect size in participants of 30-40 years of age (mean age: 36.39 ± 4.68 years). Conclusion: These results suggest that the PMS group possesses a characteristic gut microbiota. In particular, Collinsella was strongly associated with PMS. Since Collinsella has been reported to be associated with diet, dietary interventions such as prebiotics targeting Collinsella may be effective in preventing, improving, and alleviating PMS.

Fluctuations in Intestinal Microbiota Following Ingestion of Natto Powder Containing Bacillus subtilis var. natto SONOMONO Spores: Considerations Using a Large-Scale Intestinal Microflora Database.

Improving the intestinal microbiota using probiotics, prebiotics, and synbiotics has attracted attention as a method of disease prevention and treatment. This is the first study to discuss the effects of food intake on the intestinal microbiota using a large Japanese intestinal microbiota database. Here, as a case study, we determined changes in the intestinal microbiota caused by ingestion of a processed natto food containing B. subtilisvar. natto SONOMONO spores, SONOMONO NATTO POWDER CAPSULESTM, by analyzing 16S rRNA sequence data generated using next-generation sequencing techniques. The results showed that the relative abundance of Bifidobacterium and Blautia as well as the relative abundance of Bifidobacterium were increased in males and females in the ingesting group, respectively. Additionally, the effects of SONOMONO NATTO POWDER CAPSULESTM intake on Bifidobacterium and Blautia abundance depended on the relative abundance of Bifidobacterium at baseline. Finally, analysis of a large Japanese intestinal microbiota database suggested that the bacterial genera that fluctuated with the ingestion of SONOMONO NATTO POWDER CAPSULESTM may be associated with lifestyle-related diseases such as diabetes.

Neonatal gastrointestinal perforation in Japan: a nationwide survey.

PURPOSE: The purpose of this study is to identify the current clinical features of neonatal gastrointestinal perforation in Japan. METHODS: A questionnaire about cases of neonatal gastrointestinal perforation treated in recent 5 years was sent to participating institutions of the Japanese Society of Pediatric Surgeons (JSPS). RESULTS: Five hundred and thirty-six neonates with gastrointestinal perforation were treated. They consisted of 42 patients with gastric rupture/perforation (GR), 33 patients with intestinal atresia/stenosis (IA), 3 patients with malrotation (ML), 118 patients with necrotizing enterocolitis (NEC), 160 patients with focal intestinal perforation (FIP), 46 patients with meconium-related ileus (MRI), 77 patients with meconium peritonitis (MP), and 57 patients with other conditions. The total mortality rate was 20.5 %. The mortality rates of the patients with GR, IA, ML, NEC, FIP, MRI, and MP were 9.5, 9.1, 0, 33.1, 20.6, 28.2, and 9.1 %, respectively. In 263 cases involving extremely low-birth-weight neonates (ELBW), 108 died (mortality rate 41.1 %). The mortality rates for ELBW with GR, NEC, FIP, MRI, MP, and other conditions were 27.3 % (3/11), 58.5 % (48/82), 21.6 % (24/111), 70.6 % (24/34), 57.1 % (4/7), and 27.8 % (5/18), respectively. CONCLUSIONS: The mortality rates for ELBW decreased from 62.8 % in the previous survey to 41.1 % by the time of this survey.

Laparoscopic enucleation of a gastroenteric duplication cyst arising in a pancreatic tail that did not communicate with the pancreatic duct: report of a case.

Gastroenteric duplication rarely occurs in locations such as the pancreas. We report a case of gastroenteric duplication of the pancreatic tail, which was noncontiguous with the stomach and had no communication with the pancreatic duct, in a 3-year-old girl. The cyst was enucleated by laparoscopy, without the need for pancreatic resection. The optimal treatment procedures vary considerably, depending on where the gastroenteric duplication is located in the pancreas and, most importantly, whether there is communication with the pancreatic duct.

Comparison of the postoperative bowel function between transanal endorectal pull-through and transabdominal pull-through for Hirschsprung's disease: a study of the feces excretion function using an RI-defecogram.

PURPOSE: Herein, we compared the bowel function after a transabdominal and a transanal procedure for Hirschsprung's disease (HD) using the clinical score and a quantitative evaluation of the feces excretion function based on the findings of an RI-defecogram. MATERIALS AND METHODS: The subjects included 35 patients with short segment aganglionosis. In the two groups with transabdominal Z-shaped anastomosis (open group) and transanal endorectal pull-through (TEPT) (transanal group), the postoperative bowel function were evaluated based on the clinical score. In the RI-defecogram study, a time-activity curve was drawn for the (99m)Tc remaining in the rectum on defecation. The feces excretion function was thus quantified, with the time until the (99m)Tc in the rectum became 50% as T0.5 and the time until 90% of the feces were excreted from the rectum as T0.9. RESULTS: The clinical score could be evaluated in 9 cases in the open group and in 15 cases in the transanal group. No significant difference was observed in the total clinical score between the two groups, but the urge to defecate and the constipation scores in the subcategories were significantly lower in the open group. The defecogram was performed included seven cases in the open group and five cases in the transanal group. When an analysis of covariance of the two groups was conducted for the T0.5 and T0.9 values using the postoperative months as a covariate, there was a significantly negative slope, and moreover, there was a significant difference between the two groups. CONCLUSIONS: The RI-defecogram showed that feces excretion time improves with the postoperative months in both the groups, but the transanal group has higher feces excretion function in the early postoperative period compared with the open group. We consider the RI-defecogram to therefore be a useful examination method for evaluating the feces excretion function.

Patent ductus arteriosus flow patterns in the treatment of congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) mortality still remains high, due to lung hypoplasia and persistent pulmonary hypertension of the neonate (PPHN). Effective management of PPHN and time of operation are quite important to the improvement of CDH treatment. In order to determine the optimal time for operation, we monitored PPHN with cardiac ultrasound. METHODS: PPHN was assessed with three parameters: patent ductus arteriosus flow patterns (PDAFP), %left ventricular diameter at diastole, and left ventricular fraction of shortening (LVFS). Four patients with an antenatal diagnosis were treated under this protocol. Diaphragm repair was performed when PDAFP became left to right shunt dominant and the pre- and postoperative course was analyzed with regular chart reviews. RESULTS: The alveolar-arterial oxygen difference levels of four patients were 590, 335, 613 and 530 mmHg, and operations were carried out when the patients were 2, 2, 3 and 2 days old, respectively. In three of the four patients (all except case 3) the PDAFP changed from right to left shunt dominant or bidirectional (BD), to left to right shunt dominant within 48 h. The %left ventricular diameter at diastole was relatively stable around the time of operation. The LVFS of all patients decreased after the operation. Only the LVFS of case 3 decreased temporarily to less than 30% (which indicates poor left ventricular function) but recovered. No patients needed extracorporeal membrane oxygenation support. All patients survived the procedure and were extubated. Case 3, who took 10 days to become left to right shunt dominant after the operation, needed home oxygenation therapy for 10 months. CONCLUSIONS: PDAFP was a reliable marker of PPHN on a high-frequency oscillatory ventilator to determine the optimal time for the operation for CDH. The optimal time for operation is supposed to be the time when PDAFP become left to right shunt dominant.

Laparoscopic repair of late-presenting Bochdalek hernia in 2 infants.

Laparoscopic repair was performed on 2 infants with late-presenting Bochdalek hernia. Intraoperatively, the entire small intestine was herniated in 1 case and the stomach, small intestine, and part of the colon and spleen were herniated in the other case. Laparoscopic repair of Bochdalek hernia was successfully completed in both the cases. On the basis of our experience, 4 points seem important in laparoscopic surgery for Bochdalek hernia: (1) avoiding damage to the spleen while reducing organs back into the abdominal cavity; (2) ensuring visualization of diaphragmatic defect after reducing the spleen and intestinal tract; (3) ensuring sufficient width to suture the dorsal side of the diaphragm; and (4) identifying intestinal malrotation. We believe that the fourth point represents an advantage of a laparoscopic approach, which seems superior to the thoracoscopic approach and could represent a useful therapy for Bochdalek hernia in infants and older patients.

Is high amplitude propagated contraction present after transanal endorectal pull-through for Hirschsprung's disease?

The transanal endorectal pull-through (TAEPT) procedure is now widely performed for Hirschsprung's disease (HD), however, the colorectal function after TAEPT has not yet been adequately assessed. We evaluated the postoperative clinical outcome and colorectal function based on lower colonic manometry after TAEPT. Twenty-one cases of HD underwent TAEPT from 1998 to 2005. We examined the clinical outcome based on the requirement of enemas/suppositories, the number of defecations per day, the severity of perianal erosion, and the incidence of enterocolitis requiring hospital stay. Using a three-channel Dentsleeve catheter and UPS-2020 measuring device, we performed postoperative colonic manometry at three locations: (1) the anal canal, (2) 5 cm proximal to the anal canal, and (3) 10 cm proximal to the anal canal, during defecation, and then we measured the appearance of high-amplitude contraction (HAC) (duration >/=10 s, amplitude >/=100 cmH(2)O). Four of 21 cases were treated with enemas/suppositories no longer than 1 year. The number of defecations decreased gradually from 4 to 5 per day in the early postoperative period, reaching 2 to 3 per day about 1 year postoperatively. Perianal erosion was noted in 3 of 21 cases but it disappeared within three postoperative years. Two cases had enterocolitis. Lower colon manometry was performed in eight cases. Manometry during defecation was successfully monitored in six cases. HAC occurred in five of six cases (83.3%). The clinical outcomes after TAEPT were satisfactory in almost all cases. These good outcomes were possibly due to the occurrence of HAC during defecation, though HAC did not fill the definition of high amplitude propagated contractions (HAPCs). The occurrence of HAC after TAEPT might be caused by keeping any damage to the mesenteric ascending cholinergic nerve to a minimum during surgery. Further long-term observations are still required to make an adequate assessment of such cases.

Sexual problems in male patients older than 20 years with anorectal malformations.

BACKGROUND/PURPOSE: The nervi erigentes in high- and intermediate-type male anorectal malformation (ARM) runs a relatively medial course and is vulnerable in sacro-perineal dissection. These types of ARM are also associated with a high frequency of sacral anomaly, and sexual problems may be expected. However, sexual function cannot be evaluated until after the individual passes puberty. Few reports have investigated the sexual status of pubescent males with ARM. The present study evaluated sexual problems in patients with high- and intermediate-type ARM. METHODS: Sexual problems such as erectile dysfunction and ejaculatory incompetence were evaluated in 17 of 23 men aged more than 20 years who underwent operation for high- or intermediate-type ARM between September 1974 and January 2005. RESULTS: Erection angle was normal in 9 patients (52.9%), mild in 6 patients (35.3%), and dysfunctional in 2 patients (11.8%). Ejaculatory function was normal in 10 patients (58.8%), with ejaculatory incompetence in 5 patients (29.4%) and retrograde ejaculation in 2 patients (11.8%). Either erectile or ejaculatory dysfunction was present in 5 patients (29.4%), whereas both were present in 2 patients (11.8%). Sexual problems were identified in 7 patients (41.2%), with sacral anomalies in 5 (71.4%) of these 7 patients. CONCLUSIONS: Sexual problems such as erectile and ejaculatory dysfunction are common in patients with high- or intermediate-type ARM. Patients with sexual distress require persistent follow-up and continuous counselling to support their sexual problems.

Usefulness of endoscopic marking for determining the location of transanal endorectal pull-through in the treatment of Hirschsprung's disease.

In the treatment of Hirschsprung's disease, transanal endorectal pull-through (TEPT) is being performed without laparoscopic assistance or laparotomy for short-segment aganglionosis. Preoperative ascertainment of the extent of aganglionosis is required, as this affects the planning for TEPT. The present study investigated the usefulness of preoperative endoscopic marking as an intraoperative marker of the location of pull-through. Since 1998, we have performed TEPT using a prolapsing technique for the treatment of Hirschsprung's disease. Subjects comprised 17 patients with short-segment aganglionosis and 2 patients with long-segment aganglionosis in whom endoscopic marking was performed preoperatively. Median age at time of surgery was 2.7 months. The relationship between pathologic findings at the marked area and location of actual pull-through was investigated. For endoscopic marking, each patient was sedated using intravenous ketamine hydrochloride. The junction between normal bowel with peristalsis and aganglionic bowel without peristalsis ("shorebreak" finding) was marked by either tattooing or clipping. Normal ganglion cells were seen in the marked area of 14 patients, and pull-through was performed at the marked area in each of these patients. In three patients, ganglion cells existed in the marked area, but the number of ganglion cells was considered insufficient. Additional frozen sections were thus prepared to ascertain the area with normal ganglion cells, showing that normal ganglion cells were seen 1, 3 or 5 cm proximal to the marked area. In one patient, no ganglion cells were seen in the marked area, but were present 5 cm proximal to the marked area. In the remaining one patient, normal ganglion cells were seen 7 cm distal to the marked area. Pathologic findings revealed ganglion cells at the shorebreak finding in 17 of the 19 patients (89.5%), suggesting that this junction basically matches the distribution of ganglion cells. Endoscopic marking of the junction is very useful for determining the tip of pull-through.

Monitoring method for pre- and post-liver transplantation in patients with primary hyperoxaluria type I.

Differential diagnosis of primary hyperoxaluria type I (PH1) may become difficult once end-stage renal failure and anuria have occurred. Here we describe a rapid and sensitive method to simultaneously quantify glycolate and oxalate in plasma using a stable isotope dilution and gas chromatography-mass spectrometry. The results are provided within 2 h. The linearity of the method was validated up to 200 micromol/l of these compounds and the inter-assay precision for glycolate and oxalate was 2.4 and 2.6%, respectively (n=5), when the control plasma was spiked with 50 micromol/l of glycolate and oxalate. For healthy subjects, 1.0 ml of plasma was required and 0.1 ml for the PH1 patients. Using this method, plasma levels in non-PH1 patients under hemodialysis and in healthy subjects were determined. This method proved to be useful when used for differential diagnosis of PH1 and for monitoring the plasma levels of glycolate and oxalate in two PH1 patients before and after dialysis and liver transplantation. Plasma glycolate in these patients was dramatically decreased after liver transplantation, but plasma oxalate decreased more slowly due to remobilization of the calcium oxalate stores deposited throughout the body.