Obesity treatment by epigallocatechin-3-gallate-regulated bile acid signaling and its enriched Akkermansia muciniphila.

Dysregulated bile acid (BA) synthesis is accompanied by dysbiosis, leading to compromised metabolism. This study analyzes the effect of epigallocatechin-3-gallate (EGCG) on diet-induced obesity through regulation of BA signaling and gut microbiota. The data revealed that EGCG effectively reduced diet-increased obesity, visceral fat, and insulin resistance. Gene profiling data showed that EGCG had a significant impact on regulating genes implicated in fatty acid uptake, adipogenesis, and metabolism in the adipose tissue. In addition, metabolomics analysis revealed that EGCG altered the lipid and sugar metabolic pathways. In the intestine, EGCG reduced the FXR agonist chenodeoxycholic acid, as well as the FXR-regulated pathway, suggesting intestinal FXR deactivation. However, in the liver, EGCG increased the concentration of FXR and TGR-5 agonists and their regulated signaling. Furthermore, our data suggested that EGCG activated Takeda G protein receptor (TGR)-5 based on increased GLP-1 release and elevated serum PYY level. EGCG and antibiotics had distinct antibacterial effects. They also differentially altered body weight and BA composition. EGCG, but not antibiotics, increased Verrucomicrobiaceae, under which EGCG promoted intestinal bloom of Akkermansia muciniphila. Excitingly, A. muciniphila was as effective as EGCG in treating diet-induced obesity. Together, EGCG shifts gut microbiota and regulates BA signaling thereby having a metabolic beneficial effect.-Sheng, L., Jena, P. K., Liu, H.-X., Hu, Y., Nagar, N., Bronner, D. N., Settles, M. L., Bäumler, A. J. Wan, Y.-J. Y. Obesity treatment by epigallocatechin-3-gallate-regulated bile acid signaling and its enriched Akkermansia muciniphila.

The effect of synbiotics Bifidobacterium infantis and milk oligosaccharides on shaping gut microbiota community structure and NASH treatment.

Probiotic Bifidobacterium longum subspecies infantis (Bifidobacterium infantis) consumes human milk oligosaccharides (MO) and protects intestinal permeability thereby having anti-inflammatory effects (Underwood et al., 2015; Bode, 2006; Asakuma et al., 2011) [1-3]. Via the gut-liver axis, gut barrier disruption and dysbiosis lead to hepatic inflammation (Sheng et al., 2017; Jena et al., 2017) [4,5,6]. Our published data revealed that butyrate, as well as synbiotics of B. infantis in combination with MO, had protective effects against cancer-prone non-alcoholic steatohepatitis (NASH) mouse models, i.e., Western diet (WD)-fed bile acid receptor FXR (farnesoid x receptor) knockout (KO) mice (Jena et al., 2018) [6,7]. In addition, MO was particularly effective in increasing the blooming of butyrate-generating bacteria (Jena et al., 2018) [7]. In the present study, we further showed that the reduced ileal short chain fatty acid (SCFA) signaling found in WD-fed FXR KO mice could be reversed by B. infantis and/or MO treatment. Moreover, ileal mRNA levels of SCFA receptors i.e. Gpr41 (Ffar3), Gpr109 (Hcar2), and Gpr43 (Ffar2) were increased in B. infantis and/or MO-treated mice suggesting increased SCFA signaling (Fig. 1). Further, nuclear magnetic resonance (NMR) data revealed that MO and B. Infantis plus MO increased intestinal acetate, propionate, butyrate, and valerate levels (Fig. 2). In addition, B. infantis and/or MO reduced the abundance of genus Bilophila and the relative copy number of bacterial genes including dissimilatory sulfite reductase (dsrA) and methyl coenzyme M reductase A (mcrA), which were all increased in cancer-prone FXR KO mice (Fig. 3).

Synbiotics Bifidobacterium infantis and milk oligosaccharides are effective in reversing cancer-prone nonalcoholic steatohepatitis using western diet-fed FXR knockout mouse models.

Milk oligosaccharides (MO) selectively increase the growth of Bifidobacterium infantis (B. infantis). This study examines the effects of bovine MO and B. infantis in preventing nonalcoholic steatohepatitis (NASH) in Western diet (WD)-fed bile acid (BA) receptor FXR (farnesoid x receptor) knockout (KO) mice. WD-fed FXR KO mice have cancer-prone NASH and reduced B. infantis. MO and/or B. infantis supplementation improved their insulin sensitivity and reduced hepatic inflammation. Additionally, B. infantis, but not MO, decreased hepatic triglyceride and cholesterol. A combination of both further reduced hepatic cholesterol, the precursor of BAs. All three treatments modulated serum and hepatic BA profile. Moreover, B. infantis and MO decreased hepatic CYP7A1 and induced Sult2a1, Sult2a2, and Sult2a3 suggesting reduced BA synthesis and increased detoxification. Furthermore, B. infantis and MO increased ileal BA membrane receptor TGR5-regulated signaling. Together, via BA-regulated signaling, synbiotics B. infantis and MO have their unique and combined effects in reversing NASH.

Hepatic inflammation caused by dysregulated bile acid synthesis is reversible by butyrate supplementation.

Dysregulated bile acid (BA) synthesis or reduced farnesoid X receptor (FXR) levels are found in patients having metabolic diseases, autoimmune hepatitis, and liver cirrhosis or cancer. The objective of this study was to establish the relationship between butyrate and dysregulated BA synthesis-induced hepatitis as well as the effect of butyrate in reversing the liver pathology. Wild-type (WT) and FXR knockout (KO) male mice were placed on a control (CD) or western diet (WD) for 15 months. In the presence or absence of butyrate supplementation, feces obtained from 15-month-old WD-fed FXR KO mice, which had severe hepatitis and liver tumors, were transplanted to 7-month-old WD-fed FXR KO for 3 months. Hepatic phenotypes, microbiota profile, and BA composition were analyzed. Butyrate-generating bacteria and colonic butyrate concentration were reduced due to FXR inactivation and further reduced by WD intake. In addition, WD-fed FXR KO male mice had the highest concentration of hepatic ß-muricholic acid (ß-MCA) and bacteria-generated deoxycholic acid (DCA) accompanied by serious hepatitis. Moreover, dysregulated BA and reduced SCFA signaling co-existed in both human liver cancers and WD-fed FXR KO mice. Microbiota transplantation using butyrate-deficient feces derived from 15-month-old WD-fed FXR KO mice increased hepatic lymphocyte numbers as well as hepatic ß-MCA and DCA concentrations. Furthermore, butyrate supplementation reduced hepatic ß-MCA as well as DCA and eliminated hepatic lymphocyte infiltration. In conclusion, reduced butyrate contributes to the development of hepatitis in the FXR KO mouse model. In addition, butyrate reverses dysregulated BA synthesis and its associated hepatitis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

In Vitro Evaluation of Probiotic Properties of Lactic Acid Bacteria from the Gut of Labeo rohita and Catla catla.

We report the evaluation of probiotic properties of potent lactic acid bacteria (LAB) from the gut of freshwater fishes, Labeo rohita and Catla catla, for eventually developing probiotic strains for the prevention of bacterial infections in aquaculture and food preservation. Five different LAB strains were isolated and characterized for their probiotic properties. Based on physiological, morphological and biochemical characteristics, three isolates from Labeo rohita and two from Catla catla were identified as putative probiotics and were denoted as LR11, LR14 and LR16 and CC3 and CC4, respectively. Isolates CC3 and CC4 were acid (pH 2.5) and bile salt (0.3% oxygall) tolerant and exhibited strong antibacterial activities against all pathogens including Aeromonas hydrophila. In addition, all LAB isolates were susceptible to tested antibiotics, except CC3 and CC4 which were vancomycin resistant. Furthermore, the isolates CC3 and CC4 showed significantly higher in vitro cell surface properties, i.e., hydrophobicity, auto- and co-aggregation. Biochemical tests, PCR detection and 16S rRNA sequence analysis established that LR11, LR14, LR16, CC3 and CC4 are Enterococcus avium TSU11, Enterococcus pseudoavium TSU14, Enterococcus raffinosus TSU16, Lactobacillus gasseri TSU3 and Lactobacillus animalis TSU4, respectively. Studies revealed that, Lactobacillus gasseri TSU3 and Lactobacillus animalis TSU4 are ideal probiotic candidates for its use in aquaculture and require further exploratory in vivo evaluation and safety studies.

Influence of the glide path on various parameters of root canal prepared with WaveOne reciprocating file using cone beam computed tomography.

BACKGROUND: Nickel-titanium (NiTi) rotary instrumentation carries a risk of fracture, mainly as a result of flexural (fatigue fracture) and torsional (shear failure) stresses. This risk might be reduced by creating a glide path before NiTi rotary instrumentation. The aim of this study was to compare various root canal parameters with the new WaveOne single-file reciprocating system in mesial canals of mandibular molars with and without glide path using cone beam computed tomography (CBCT). MATERIALS AND METHODS: One hundred mandibular molar teeth with canal curvature between 20° and 30° were divided into two groups of 50 teeth each. In Group 1, no glide path was created, whereas in Group 2, a glide path was created with PathFiles at working length (WL). In both groups, canals were shaped with WaveOne primary reciprocating files to the WL. Canals were scanned in a CBCT unit before and after instrumentation. Postinstrumentation changes in canal curvature, cross-sectional area, centric ability, residual dentin thickness, and the extent of canal transportation were calculated using image analysis software and subjected to statistical analysis. Data were analyzed using Student's t-test and Mann-Whitney U-test (P < 0.05). RESULTS: The mean difference of root canal curvature, cross-sectional area, centric ability, and residual dentin thickness increased, whereas it reduced significantly for canal transportation in Group 2. CONCLUSION: WaveOne NiTi files appeared to maintain the original canal anatomy and the presence of a glide path further improves their performance and was found to be beneficial for all the parameters tested in this study.

Evaluation of endometrium in peri-menopausal abnormal uterine bleeding.

Abnormal Uterine Bleeding (AUB) is one of the most common health problems encountered by women. It affects about 20% women of reproductive age, and accounts for almost two thirds of all hysterectomies. Gynaecologists are often unable to identify the cause of abnormal bleeding even after a thorough history and physical examination. Diagnostic evaluations and treatment modalities have been evolving over time. The onus in AUB management is to exclude complex endometrial hyperplasia and endometrial cancer. From D and C + EUA under general anesthesia the shift to more accurate procedures like hysteroscopy and vision directed biopsy was welcome. But the current minimally invasive procedures like sonohysterography, office vacuum aspiration (Pipelle) and the use of office hysteroscopy have revolutionized the management of AUB. We have tried to review the current literature and guidelines for evaluation of endometrium with the twin goals of finding an accurate reason causing the AUB and to rule out endometrial cancer or a potential for the cancer in future. We have also attempted to compare the current procedures and their present perspective vis-à-vis each other. Histological assessment is the final word, but obtaining a sample for histology makes it more accurate, and we have reviewed these techniques to enhance accuracy in diagnosis. Hysteroscopy and directed biopsy is the 'gold standard' approach for most accurate evaluation of endometrium to rule out focal endometrial Ca. Blind endometrial biopsies should no longer be performed as the sole diagnostic strategy in perimenopausal as well as in postmenopausal women with AUB. A single-stop approach, especially in high risk women (Obesity, diabetes, family history of endometrial, ovarian or breast cancer) as well as in women with endometrial hyperplasia of combining the office hysteroscopy, directed biopsy in presence of a focal lesion, and vacuum sampling of endometrium in normal looking endometrium, all without anesthesia is the most minimally invasive and yet accurate approach in current practice.