Persistence of gut dysbiosis in individuals with anorexia nervosa.

Recent evidence suggests a crucial role of the gut microbiota in the pathogenesis of anorexia nervosa (AN). In this study, we carried out a series of multiple analyses of the gut microbiota of hospitalized individuals with AN over three months using 16S or 23S rRNA-targeted reverse transcription-quantitative polymerase chain reaction (PCR) technology (YIF-SCAN®), which is highly sensitive and enables the precise quantification of viable microorganisms. Despite the weight gain and improvements in psychological features observed during treatment, individuals with AN exhibited persistent gut microbial dysbiosis over the three-month duration. Principal component analysis further underscored the distinct microbial profile of individuals with AN, compared with that of age-matched healthy women at all time points. Regarding the kinetics of bacterial detection, the detection rate of Lactiplantibacillus spp. significantly increased after inpatient treatment. Additionally, the elevation in the Bifidobacterium counts during inpatient treatment was significantly correlated with the subsequent body weight gain after one year. Collectively, these findings suggest that gut dysbiosis in individuals with AN may not be easily restored solely through weight gain, highlighting the potential of therapeutic interventions targeting microbiota via dietary modifications or live biotherapeutics.

Correction to: Very long chain fatty acids are an important marker of nutritional status in patients with anorexia nervosa: a case control study.

[This corrects the article DOI: 10.1186/s13030-020-00186-8.].

Very long chain fatty acids are an important marker of nutritional status in patients with anorexia nervosa: a case control study.

BACKGROUND: Anorexia nervosa (AN) is a disease resulting in extreme weight loss. It is caused by multiple factors, including psychosocial, environmental, and genetic factors. A genetic abnormality affecting lipid metabolism has been recently reported in patients with AN. However, it is unknown whether lipid metabolism abnormalities in AN are caused by eating behavior, undernutrition, and/or genetic factors. The meaning of lipid metabolism in AN remains unclear. In particular, differences in the profiles of very long-chain fatty acids (VLCFAs) in patients with various types of AN have not been studied. This study aimed to determine changes to the fatty acid profile over a 3-month period, specifically that of long-chain fatty acids (LCFAs) and VLCFAs in patients with various types of AN. METHODS: We evaluated 69 female patients with AN, subclassified as AN-restricting type (AN-R) and AN-Binge-Eating/Purging type (AN-BP). On admission and after 3 months of treatment, height, weight, body mass index, plasma and serum parameters, and plasma fatty acid concentrations were measured in all patients. The control group included 25 healthy, age-matched women. Comparisons between the groups were made using one-way ANOVA, while those between the various parameters at admission and after 3 months within each group were made using the Wilcoxon signed rank test. RESULTS: On admission, the AN-R and the AN-BP groups had significantly higher levels of 18-24C and > 14C fatty acids (LCFAs and VLCFAs, respectively) than the control group. After 3 months of treatment, both groups showed high levels of 14-24C fatty acids. The levels of VLCFAs (C22:0 and C24:0) and LCFA (C18:3) after 3 months of treatment remained high in both AN groups relative to the control group. CONCLUSIONS: Eating behaviors appear to be associated with levels of LCFAs. Lipid metabolism abnormalities under conditions of starvation in AN might have a genetic basis and appear to be associated with VLCFA (C22:0 and C24:0) and LCFA (C18:3) levels.

Impact of Branched-Chain Amino Acid Granule Therapy in Patients with Hepatocellular Carcinoma Who Have Normal Albumin Levels and Low Branched-Chain Amino Acid to Tyrosine Ratios.

Serum albumin has been reported to be a useful indicator of liver function and branched-chain amino acid (BCAA) therapy is associated with a lower incidence of hepatocellular carcinoma (HCC). We investigated the impact of BCAA granule therapy on overall survival and disease-specific survival in patients with normal albumin levels and low BCAA to tyrosine ratio (BTR)s who had treatment-naïve HCC. Overall survival and disease-specific survival was analyzed in 78 patients with HCC who were treated (n = 27) or not treated (n = 51) with BCAAs. Twenty-six patients died during the follow-up period. There were 19, 5, and 2 patients who died due to HCC, hepatic failure, and non-liver-related disease, respectively. Multivariate analysis for factors associated with overall survival indicated that BCAA therapy was independently associated with good prognosis in patients with HCC (hazard ratio [HR], 0.317; 95% confidence interval [CI], 0.123-0.813; P = 0.017). In addition, multivariate analysis using competing risks methods indicated that BCAA therapy is independently associated with reduction of disease-specific mortality (HR, 0.216; 95% CI, 0.068-0.689; P = 0.001). In conclusion, BCAA therapy improved both overall survival and disease-specific survival in HCC patients with low BTRs despite having normal albumin levels.

Influence of renal dysfunction on dose reduction and virologic efficacy of regimens combining ribavirin and all-oral direct acting antivirals in patients with chronic hepatitis C virus infection.

AIM: Several interferon (IFN)-free, all-oral regimens with direct acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection also include ribavirin (RBV). We investigated the influence of renal dysfunction on virologic efficacy and adverse effects in 189 patients with HCV genotype 2 infection who received combination RBV-DAA regimens. METHODS: The incidence of RBV-induced anemia, RBV dose reduction, and virologic efficacy were compared according to baseline renal function as defined by the estimated glomerular filtration rate (eGFR). RESULTS: Patients with renal dysfunction (eGFR = 30-59 mL/min/1.73 m2 ) had higher rate of RBV dose reduction and more marked decreases in hemoglobin levels. These findings were more pronounced in patients with the ITPA CC genotype, who are more sensitive to RBV-induced anemia. Although there were no statistically significant differences in sustained virologic response (SVR) rates according to renal function overall (P = 0.1650), the SVR rate was significantly lower in patients who required RBV dose reduction than in those who did not (P < 0.0001). CONCLUSIONS: Baseline renal dysfunction could unfavorably affect the outcomes of RBV-DAA in patients with chronic HCV infection due to the increased risk of RBV dose reduction, even in the era of IFN-free DAA regimens.

Ghrelin activation and neuropeptide Y elevation in response to medium chain triglyceride administration in anorexia nervosa patients.

BACKGROUND & AIMS: Ghrelin, a peptide found in the stomach, increases appetite and fat-free mass while suppressing energy expenditure. Ghrelin requires modification by medium-chain triglycerides (MCTs) to exert its physiological effects. In this study, we investigated ghrelin activation and the resulting physiological changes following MCT administration. METHODS: Thirty participants were selected from among inpatients diagnosed with anorexia nervosa (AN). The patients were randomly divided into three groups by the MCT content of their nutritional supplement: (1) 'MCT high' (>6 g/day), (2) 'MCT moderate' (1-6 g/day), and (3) 'MCT low' (<1 g/day). Physical factors such as body weight and composition, as well as levels of nutrition-related serum factors such as acylated (active form) and desacyl (inactive form) ghrelin, leptin, growth hormone, insulin-like growth factor, and neuropeptide Y (NPY) were measured at weeks 0, 2, 4, and 6 of the treatment protocol. RESULTS: Significantly higher ghrelin activation was found in the 'MCT high' than in the 'MCT low' group (P < 0.05). The amount of consumed MCT had a curvilinear relationship with the active ghrelin level (P = 0.00). NPY levels in the 'MCT high' group were significantly more elevated than in the 'MCT low' group (P < 0.05). MCT administration did not significantly affect the remaining factors. CONCLUSIONS: This study clearly demonstrated that MCT activates ghrelin and increases NPY, suggesting that nutritional supplementation with MCT may be effective for the treatment of AN patients in an emaciated state.

The outcome of treatment for anorexia nervosa inpatients who required urgent hospitalization.

BACKGROUND: This study was done to determine which psychosocial factors are related to the urgent hospitalization of anorexia nervosa patients (AN) due to extremely poor physical condition and to evaluate their outcome after inpatient treatment. METHODS: 133 hospitalized AN patients were classified into an urgent hospitalization (n = 24) or a planned hospitalization (n = 109) group. Multiple regression analysis was done of clinical features, body mass index (BMI), psychological tests [The Minnesota Multiphasic Personality Inventory (MMPI), alexithymia, relationship with parents, and the Eating Disorder Inventory (EDI)]. The effectiveness of treatment was prospectively determined two years after discharge by the Global Clinical Score (GCS). The hospitalized weight gain and the frequency of outpatient visits were evaluated. RESULTS: Of the factors assessed, only BMI at admission was related to the necessity of urgent hospitalization (ß = - 1.063, P = 0.00). The urgent group had significantly more weight loss after discharge and poorer social adaptation on the GCS, even when the patient had a sufficient increase in body weight during inpatient treatment and an equivalent number of outpatient consultations. CONCLUSION: None of the parameters of the psychosocial tests studied were significantly different between the groups. The outcome of the urgent group was poor. Two years after discharge they had difficulty maintaining weight and continued to have poor social adaptation.

Streptococcus thermophilus ST28 ameliorates colitis in mice partially by suppression of inflammatory Th17 cells.

The effects of Streptococcus thermophilus ST28 on cytokine production by murine splenocytes stimulated with transforming growth factor-ß plus interleukin- (IL-) 6 were evaluated. The addition of ST28 significantly repressed IL-17 production compared to ATCC 19258 (type strain). ST28 also decreased the number of Th17 cells in the stimulated splenocytes. The anti-inflammatory effects of ST28 administration were evaluated in mice with colitis induced by dextran sodium sulphate (DSS). Oral treatment of mice with ST28 ameliorated the intestinal lesions by DSS. Upon DSS treatment, IL-17 production in lamina propria lymphocytes (LPLs) was induced, but ST28 significantly decreased its production. ST28 also decreased the percentage of Th17 cells in LPL from DSS-induced colitis. The present results imply that ST28 suppresses the Th17 response in inflamed intestines and would be useful in the treatment of Th17-mediated diseases, such as inflammatory bowel disease.

[Aging and anti-aging of oocytes].

The functions of organs decrease as the age increases. The fecundity of women also decreases due to mainly the decreasing quality of oocytes. The recent change of life style makes the age of infertility patients elder and infertility treatments more difficult. The therapeutic strategy for the elder infertility patients is still chaotic. The precise evaluation for the ageing in the female genital organs should be developed and the treatment for the failure of fecundity due to aging must be overcome.

Continuous cell partitioning using an aqueous two-phase flow system in microfluidic devices.

We present a novel microfluidic system in which an aqueous two-phase laminar flow is stably formed, and the continuous partitioning of relatively large cells can be performed, eliminating the influence of gravity. In this study, plant cell aggregates whose diameters were 37-96 microm were used as model particles. We first performed cell partitioning using a simple straight microchannel having two inlets and two outlets and examined the effects of the flow rate and the phase width on partitioning efficiency. Second, by using a microchannel with a pinched segment, the partitioning efficiency was successfully improved. This microscale aqueous two-phase flow system can further be incorporated into micro total analysis systems (microTAS) or lab-on-a-chip technology, owing to its simplicity, applicability, and biocompatibility.

Pinched flow fractionation: continuous size separation of particles utilizing a laminar flow profile in a pinched microchannel.

A concept of "pinched flow fractionation" for the continuous size separation and analysis of particles in microfabricated devices has been proposed and demonstrated. In this method, particles suspended in liquid were continuously introduced into a microchannel having a pinched segment and were aligned to one sidewall in the pinched segment by another liquid flow without particles. The particles were then separated perpendicularly to the flow direction according to their sizes by the spreading flow profile inside the microchannel. Polymer microbeads were successfully separated, and the effects of the flow rate and channel shapes on the separation performance were examined. Also, separated particles were collected independently by making branches at the end of the pinched segment. Since this method utilizes only the laminar flow profile inside a microchannel, complicated outer field control could be eliminated, which is usually required for other kinds of particle separation methods such as field flow fractionation. Also, this method can be applied both for particle size analysis and for preparation of monodispersed particles, since separation can be rapidly and continuously performed.