Bile salts

INTRODUCTION: Progressive familial intrahepatic cholestasis (PFIC) is a group of disorders characterized by inappropriate bile formation, causing hepatic accumulation of bile acids and, subsequently, liver injury. Until recently, no approved treatments were available for these patients. AREAS COVERED: Recent clinical trials for PFIC treatment have focused on intestine-restricted ileal bile acid transporter (IBAT) inhibitors. These compounds aim to reduce the pool size of bile acids by interrupting their enterohepatic circulation...

Despite technological advances in the proteomics field, sample preparation still represents the main bottleneck in mass spectrometry (MS) analysis. Bead-based protein aggregation techniques have recently emerged as an efficient, reproducible, and high-throughput alternative for protein extraction and digestion. Here, a refined paramagnetic bead-based digestion protocol is described for Opentrons® OT-2 platform (OT-2) as a versatile, reproducible, and affordable alternative for the automatic sample preparation for MS analysis...

Mounting evidence has shown that the gut microbiota plays a key role in human health. The homeostasis of the gut microbiota could be affected by many factors, including environmental chemicals. Aldicarb is a carbamate insecticide used to control a variety of insects and nematode pests in agriculture. Aldicarb is highly toxic and its wide existence has become a global public health concern. In our previous study, we have demonstrated that aldicarb disturbed the gut microbial community structure and composition...

Bile acids are bioactive metabolites that are biotransformed into secondary bile acids by the gut microbiota, a vast consortium of microbes that inhabit the intestines. The first step in intestinal secondary bile acid metabolism is carried out by a critical enzyme, bile salt hydrolase (BSH), that catalyzes the gateway reaction that precedes all subsequent microbial metabolism of these important metabolites. As gut microbial metabolic activity is difficult to probe due to the complex nature of the gut microbiome, approaches are needed to profile gut microbiota-associated enzymes such as BSH...

Obesity is a global pandemic, thus novel developments that reduce the absorption of fats is of interest. We have evaluated the effect of graphene oxide (GO) on the lipase catalyzed hydrolysis of fats (tributyrin, sunflower and olive oil) under simulated duodenal conditions. Results indicate that the presence of GO in the digestion mixture can inhibit lipase activity up to a 90% of the initial reaction rate, and this inhibition lasts even during 2 h of digestion. The inhibition mechanism seems non competitive and could be opposite to the effect of bile salts, although the direct interaction between GO and the enzyme cannot be discarded...

The survivability of encapsulated and nonencapsulated probiotics consisting of Lactobacillus acidophilus and Lacticaseibacillus casei and the nutritional, physicochemical, and sensorial features of cottage cheese were investigated under refrigeration storage at 4 °C for 28 days. Microbeads of L. acidophilus and L. casei were developed using 2% sodium alginate, 1.5% sodium alginate and 0.5% carrageenan, and 1% sodium alginate and 1% carrageenan using an encapsulation technique to assess the probiotic viability in cottage cheese under different gastrointestinal conditions (SGF (simulated gastric juice), SIF (simulated intestinal fluid)), and bile salt) and storage conditions...

Shigella flexneri causes severe diarrheal disease worldwide. While many aspects of pathogenesis have been elucidated, significant knowledge gaps remain regarding the role of putative chromosomally-encoded virulence genes. The uncharacterized sap gene encoded on the chromosome has significant nucleotide sequence identity to the fluffy ( flu ) antigen 43 autotransporter gene in pathogenic Escherichia coli . Here, we constructed a Δ sap mutant in S. flexneri strain 2457T and examined the effects of this mutation on bacterial cell aggregation, biofilm formation, and adherence to colonic epithelial cells...

Human Na+ taurocholate co-transporting protein (hNTCP) is a key bile salt transporter to maintain enterohepatic circulation and is responsible for the recognition of hepatitis B and D viruses (HBV/HDV). Despite landmark cryo-EM studies revealing open-pore and inward-facing states of NTCP stabilized by antibodies, the transport mechanism remains largely unknown. To address this knowledge gap, we used molecular dynamics (MD) and enhanced sampling Metadynamics simulations to elucidate the intrinsic mechanism of hNTCP-mediated taurocholate acid (TCA) transport driven by Na+ -binding...

With rising infection rates in recent years, Vibrio vulnificus poses an increasing threat to public safety in the coastal brackish Baltic Sea. It is therefore important to monitor this organism and assess the V. vulnificus infection risk on a more regular basis. However, as the coastline of the Baltic Sea is 8000 km long and shared by nine nations, a convenient, fast, inexpensive, yet efficient V. vulnificus identification method is essential. We evaluated the effectiveness of a two-step agar-based approach consisting of successive Vibrio isolation and cultivation on thiosulphate-citrate-bile salt sucrose (TCBS) agar and CHROMagar™ Vibrio for V...

Cholera, a deadly diarrheal disease, continues to ravage various parts of the world. It is caused by Vibrio cholerae , an important member of the gamma-proteobacteria. Based on certain genetic and phenotypic tests, the organism is classified into two major biotypes, namely classical and El Tor. The El Tor and its variants are majorly responsible for the ongoing seventh pandemic across the globe. Previously, we have shown that cross-feeding of glucose metabolic acidic by-products of gut commensals can severely affect the viability of the biotypes...

Bacterial spore-forming Bacillaceae species, including Bacillus subtilis and Heyndrickxia coagulans , are increasingly utilized for probiotic dietary supplementation. Bacillus velezensis is a Bacillus species that is frequently used as a direct-fed microbial in animal feed but less so as a probiotic for humans. The objective of this study was to characterize the suitability of the Bacillus velezensis strain BV379 for probiotic applications by (1) in silico screening for both adverse genetic elements and putatively beneficial traits, (2) in vitro evaluation of interactions with human intestinal epithelial cells, and (3) in vitro characterization of BV379 spore viability at various temperatures, pH, and in the presence of bile salt...

The farnesoid X receptor (FXR) has been recognized as a potential drug target for the treatment of non-alcoholic fatty liver disease (NAFLD). FXR agonists benefit NAFLD by modulating bile acid synthesis and transport, lipid metabolism, inflammation, and fibrosis pathways. However, there are still great challenges involved in developing safe and effective FXR agonists. To investigate the critical factors contributing to their activity on the FXR, 3D-QSAR molecular modeling was applied to a series of isoxazole derivatives, using comparative molecular field analysis (CoMFA (q2 = 0...

Lactococcus lactis is a lactic acid bacterium (LAB), generally recognized as safe, and has been widely used in the food industry, especially in fermented dairy products. Numerous studies have evaluated the technological and probiotic properties of lactococci; however, few studies have reported the probiotic characteristics of L. lactis strains isolated from dairy products. In this work, probiotic potential, including survival in simulated gastric juice, tolerance to bile salts, hydrophobicity, and auto- and co-aggregation, was evaluated in L...

Cholesterol-7-alpha hydroxylase (CYP7A1) is a key enzyme in the synthesis of bile salts, and its activity can contribute to determining cholesterol levels and, consequently, the risk of developing coronary atherosclerotic disease. We evaluated whether seven (rs3808607 G/T , rs9297994 G/A , rs10504255 A/G , rs8192870 G/T , rs2081687 C/T , rs1457043 C/T, and rs10107182 C/T) polymorphisms located in the promoter and enhancer regions of the CYP7A1 gene, which have not been sufficiently explored, are candidates of risk markers of acute coronary syndrome (ACS) in the Mexican population...

BACKGROUND: While particular strains within the Bacillus species, such as Bacillus subtilis, have been commercially utilised as probiotics, it is critical to implement screening assays and evaluate the safety to identify potential Bacillus probiotic strains before clinical trials. This is because some Bacillus species, including B. cereus and B. anthracis, can produce toxins that are harmful to humans. RESULTS: In this study, we implemented a funnel-shaped approach to isolate and evaluate prospective probiotics from homogenised food waste - sesame oil meal (SOM)...

Probiotic microorganisms are used to improve the health and wellness of people and the research on this topic is of current relevance and interest. Fifty-five yeasts, coming from honeybee's ecosystem and belonging to Candida, Debaryomyces, Hanseniaspora, Lachancea, Metschnikowia, Meyerozyma, Starmerella and Zygosacchromyces genera and related different species, were evaluated for the probiotic traits. The resistance to gastrointestinal conditions, auto-aggregation, cell surface hydrophobicity or biofilm formation abilities as well as antimicrobial activity against common human pathogenic bacteria were evaluated...

OBJECTIVE: To utilize the global system analysis (GSA) in oral absorption modeling to gain a deeper understanding of system behavior, improve model accuracy, and make informed decisions during drug development. METHODS: GSA was utilized to give insight into which drug substance (DS), drug product (DP), and/or physiological parameter would have an impact on peak plasma concentration (Cmax ) and area under the curve (AUC) of dipyridamole as a model weakly basic compound...

Two probiotic candidates, Lactobacillus reuteri C1 (C1) and Lactobacillus acidophilus C5 (C5), which were previously isolated from canines, were evaluated in the present study. L. reuteri and L. acidophilus have anti-oxidant, anti-inflammatory, immune-enhancing, and anti-cancer properties and exhibit various probiotic effects in humans and animals. The strains C1 and C5 demonstrated good tolerance to acid and bile salt exposure, exhibited effective adhesion to HT-29 cell monolayer, and displayed sensitivity to antibiotics, thus affirming their probiotic characteristics...

Bacteroides thetaiotaomicron is a prominent member of the human gut microbiota contributing to nutrient exchange, gut function, and maturation of the host's immune system. This obligate anaerobe symbiont can adopt a biofilm lifestyle, and it was recently shown that B. thetaiotaomicron biofilm formation is promoted by the presence of bile. This process also requires a B. thetaiotaomicron extracellular DNase, which is not, however, regulated by bile. Here, we showed that bile induces the expression of several Resistance-Nodulation-Division (RND) efflux pumps and that inhibiting their activity with a global competitive efflux inhibitor impaired bile-dependent biofilm formation...

The mucus layer in the small intestine is generally regarded as a barrier to drug absorption. However, the mucus layer is a complex system, and presently, only a few studies have been conducted to elucidate its physicochemical properties. The current study hypothesizes that the mucus layer contains solubility-enhancing surfactants and thus might aid the oral absorption of poorly water-soluble drugs. Mucus was sampled from sections of the small intestine of fasted rats to analyze the rheological properties and determine the mucus pH and concentrations of proteins and endogenous surfactants, i...