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Different effects of two newly-isolated probiotic Lactobacillus plantarum 15HN and Lactococcus lactis subsp. Lactis 44Lac strains from traditional dairy products on cancer cell lines

Haghshenas B, Abdullah N, Nami Y, Radiah D, Rosli R, Khosroushahi AY

Anaerobe, 2014 Dec;30:51-9.
PMID: 25168457 DOI: 10.1016/j.anaerobe.2014.08.009

Lactobacillus and Lactococcus strains isolated from food products can be introduced as probiotics because of their health-promoting characteristics and non-pathogenic nature. This study aims to perform the isolation, molecular identification, and probiotic characterization of Lactobacillus and Lactococcus strains from traditional Iranian dairy products. Primary probiotic assessments indicated high tolerance to low pH and high bile salt conditions, high anti-pathogenic activities, and susceptibility to high consumption antibiotics, thus proving that both strains possess probiotic potential. Cytotoxicity assessments were used to analyze the effects of the secreted metabolite on different cancer cell lines, including HT29, AGS, MCF-7, and HeLa, as well as a normal human cell line (HUVEC). Results showed acceptable cytotoxic properties for secreted metabolites (40 μg/ml dry weight) of Lactococcus lactis subsp. Lactis 44Lac. Such performance was similar to that of Taxol against all of the treated cancer cell lines; however, the strain exhibited no toxicity on the normal cell line. Cytotoxic assessments through flow cytometry and fluorescent microscopy demonstrated that apoptosis is the main cytotoxic mechanism for secreted metabolites of L. lactis subsp. Lactis 44Lac. By contrast, the effects of protease-treated metabolites on the AGS cell line verified the protein nature of anti-cancer metabolites. However, precise characterizations and in vitro/in vivo investigations on purified proteins should be conducted before these metabolites are introduced as potential anti-cancer therapeutics.

Matched MeSH terms: Bile Acids and Salts/metabolism
Fulltext Prediagnostic Plasma Bile Acid Levels and Colon Cancer Risk: A Prospective Study

Kühn T, Stepien M, López-Nogueroles M, Damms-Machado A, Sookthai D, Johnson T, et al.

J Natl Cancer Inst, 2020 May 01;112(5):516-524.
PMID: 31435679 DOI: 10.1093/jnci/djz166

BACKGROUND: Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans.
METHODS: Associations between prediagnostic plasma levels of 17 primary, secondary, and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations.
RESULTS: Positive associations were observed between colon cancer risk and plasma levels of seven conjugated bile acid metabolites: the primary bile acids glycocholic acid (ORquartile 4 vs quartile 1= 2.22, 95% confidence interval [CI] = 1.52 to 3.26), taurocholic acid (OR = 1.78, 95% CI = 1.23 to 2.58), glycochenodeoxycholic acid (OR = 1.68, 95% CI = 1.13 to 2.48), taurochenodeoxycholic acid (OR = 1.62, 95% CI = 1.11 to 2.36), and glycohyocholic acid (OR = 1.65, 95% CI = 1.13 to 2.40), and the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95% CI = 1.12 to 2.54) and taurodeoxycholic acid (OR = 1.54, 95% CI = 1.02 to 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk.
CONCLUSIONS: This prospective study showed that prediagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.

Matched MeSH terms: Bile Acids and Salts/blood*
Fulltext Prediagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma

Stepien M, Lopez-Nogueroles M, Lahoz A, Kühn T, Perlemuter G, Voican C, et al.

Int J Cancer, 2022 Apr 15;150(8):1255-1268.
PMID: 34843121 DOI: 10.1002/ijc.33885

Bile acids (BAs) play different roles in cancer development. Some are carcinogenic and BA signaling is also involved in various metabolic, inflammatory and immune-related processes. The liver is the primary site of BA synthesis. Liver dysfunction and microbiome compositional changes, such as during hepatocellular carcinoma (HCC) development, may modulate BA metabolism increasing concentration of carcinogenic BAs. Observations from prospective cohorts are sparse. We conducted a study (233 HCC case-control pairs) nested within a large observational prospective cohort with blood samples taken at recruitment when healthy with follow-up over time for later cancer development. A targeted metabolomics method was used to quantify 17 BAs (primary/secondary/tertiary; conjugated/unconjugated) in prediagnostic plasma. Odd ratios (OR) for HCC risk associations were calculated by multivariable conditional logistic regression models. Positive HCC risk associations were observed for the molar sum of all BAs (ORdoubling = 2.30, 95% confidence intervals [CI]: 1.76-3.00), and choline- and taurine-conjugated BAs. Relative concentrations of BAs showed positive HCC risk associations for glycoholic acid and most taurine-conjugated BAs. We observe an association between increased HCC risk and higher levels of major circulating BAs, from several years prior to tumor diagnosis and after multivariable adjustment for confounders and liver functionality. Increase in BA concentration is accompanied by a shift in BA profile toward higher proportions of taurine-conjugated BAs, indicating early alterations of BA metabolism with HCC development. Future studies are needed to assess BA profiles for improved stratification of patients at high HCC risk and to determine whether supplementation with certain BAs may ameliorate liver dysfunction.

Matched MeSH terms: Bile Acids and Salts/blood*
Clinical evaluation of dactilase: a eutonic preparation for the treatment of digestive disorders

Jefferson NC

Med J Malaya, 1967 Jun;21(4):322-5.
PMID: 4230499
Matched MeSH terms: Bile Acids and Salts/therapeutic use*
Acid and bile tolerance of Lactobacillus isolated from chicken intestine

Jin LZ, Ho YW, Abdullah N, Jalaludin S

Lett Appl Microbiol, 1998 Sep;27(3):183-5.
PMID: 9750324

Twelve Lactobacillus strains isolated from chicken intestine were used to investigate acid and bile tolerance in vitro. Ten out of the 12 strains were slightly affected by 0.3% bile salts, showing a delay of growth (d) of 0.6-37.2 min compared with growth in control cultures. Two strains were not affected by the bile salts. Of the 12 strains, seven could be arbitrarily classified as resistant (d < 15 min) and five as tolerant (15 min < d < or = 40 min). Lactobacillus strains from the caecum showed better tolerance to acid than those from the ileum. Generally, the survival of the ileal strains was very low at pH 1.0 and 2.0, and moderate at pH 3.0. In contrast, caecal Lactobacillus strains could survive at pH 1.0 for up to 2 h of incubation; growth was moderate at pH 2.0 and good at pH 3.0 and 4.0.

Matched MeSH terms: Bile Acids and Salts/pharmacology*
Fulltext Novel probiotic lactic acid bacteria isolated from indigenous fermented foods from West Sumatera, Indonesia

Harnentis H, Marlida Y, Nur YS, Wizna W, Santi MA, Septiani N, et al.

Vet World, 2020 Sep;13(9):1922-1927.
PMID: 33132606 DOI: 10.14202/vetworld.2020.1922-1927

Background and Aim: Probiotics play an important role in maintaining a healthy gut and consequently promote good health. This study aimed to find novel probiotic lactic acid bacteria (LAB) from indigenous fermented foods of West Sumatera, Indonesia.
Materials and Methods: This study utilized 10 LAB previously isolated from fermented buffalo milk (dadih), fermented fish (budu), and fermented cassava (tape) which have the ability to produce gamma-aminobutyric acid. The study commenced with the screening of LAB for certain properties, such as resistance to acid and bile salts, adhesion to mucosal surface, and antagonism against enteric pathogens (Escherichia coli, Salmonella Enteritidis, and Staphylococcus aureus). The promising isolates were identified through biochemical and gram staining methods.
Results: All isolates in this study were potential novel probiotics. They survived at a pH level of 2.5 for 3 h (55.27-98.18%) and 6 h (50.98-84.91%). Survival in bile at a concentration of 0.3% was 39.90-58.61% and the survival rate was 28.38-52.11% at a concentration of 0.5%. The inhibitory diameter ranged from 8.75 to 11.54 mm for E. coli, 7.02 to 13.42 mm for S. aureus, and 12.49 to 19.00 mm for S. Enteritidis. All the isolates (84.5-92%) exhibited the ability to adhere to mucosal surfaces. This study revealed that all the isolates were potential probiotics but N16 proved to be superior because it was viable at a pH level of 2 (84.91%) and it had a good survival rate in bile salts assay (55.07%). This isolate was identified as Lactobacillus spp., Gram-positive bacilli bacteria, and tested negative in both the catalase and oxidase tests.
Conclusion: All the isolates in this study may be used as probiotics, with isolate N16 (Lactobacillus spp.) as the most promising novel probiotic for poultry applications based on its ability to inhibit pathogenic bacteria.

Matched MeSH terms: Bile Acids and Salts
Fulltext Familial hypercholesterolaemia: an updated overall management

Noor Alicezah Mohd Kasim, Chua Yung An, Hapizah Nawawi

Journal of Clinical and Health Sciences, 2020;5(2):19-38.
MyJurnal

Familial hypercholesterolaemia (FH), the commonest and serious but potentially treatable
form of inherited dyslipidaemias, is characterised by severely elevated plasma low-density
lipoprotein-cholesterol (LDL-C) level, which subsequently leads to premature coronary artery
disease (pCAD). Effectiveness of FH early detection and treatment is supported by the
outcome of several international cohort studies. Optimal FH management relies on
prescription of statins either alone or together with other lipid-lowering therapies (LLT).
Intensive lifestyle intervention is required in parallel with LLT, which should be commenced at
diagnosis in adults and childhood. Treatment with high intensity statin should be started as
soon as possible. Combination with ezetimibe and/or bile acid sequestrants is indicated if
target LDL-C is not achieved. For FH patients in the very-high risk category, if their LDL-C
targets are not achieved, despite being on maximally tolerated statin dose and ezetimibe,
proprotein convertase subtilisin/kexin type1 inhibitor (PCSK9i) is recommended. In statin
intolerance, ezetimibe alone, or in combination with PCSK9i may be considered. Clinical
evaluation of response to treatment and safety are recommended to be done about 4-6 weeks
following initiation of treatment. Homozygous FH (HoFH) patients should be treated with
maximally tolerated intensive LLT and, when available, with lipoprotein apheresis. This review
highlights the overall management, and optimal treatment combinations in FH in adults and
children, newer LLT including PCSK9i, microsomal transfer protein inhibitor, allele-specific
oligonucleotide to ApoB100 and PCSK9 mRNA. Family cascade screening and/or screening
of high-risk individuals, is the most cost-effective way of identifying FH cases and initiating
early and adequate LLT.

Matched MeSH terms: Bile Acids and Salts
Fulltext CHARACTERISATION OF LACTIC ACID BACTERIA ISOLATED FROM KEFIR MILK MADE FROM DAIRY AND NON-DAIRY SOURCES AND THEIR SENSORY ACCEPTANCE

CHAN KHER ZHI, MOHD NIZAM LANI, MOHD NIZAM LANI, YUSNITA HAMZAH, FAUZIAH TUFAIL AHMAD, HAFIZAH NIK UBAIDILLAH

UMT Journal of Undergraduate Research, 2021;3(2):37-50.
MyJurnal

Kefir is a fermented milk obtained by fermenting milk with kefir grains. The chemical composition ofdairy and non-dairy sources may affect the growth and characterisation of lactic acid bacteria (LAB). In this study, different sources of milk (cow milk) and non-dairy milk (soymilk and coconut milk) were used as the fermentation media for kefir products. The objectives of the study were to isolate and characterise LAB from kefir drink produced from dairy and non-dairy milk. LAB was isolated using different cultural methods, such as MRS Agar, MRS with 0.8% CaCO3, and M17 Agar. The characteristics of the LAB isolates were determined using morphological, biochemical tests and the API 50 CHL kit. The physicochemical composition of the samples was determined using titratable acidity and pH level. Sensory evaluation of the kefir drink samples was also carried out. Results confirmed that the isolates were identified as Lactobacillus buchneri, Lactobacillus brevis 1, Leuconostoc mesenteroides, Lactobacillus acidophilus 3and Lactobacillus plantarum 1. The L. buchneri, L. brevis, Leu. mesenteroides and L. acidophilus are heterofermentative bacteria, whereas L. plantarum is a homofermentative bacterium. Four LAB isolates have the potential to be used as probiotic strains due to their high resistant to low pH and bile salt. The sensory scores of these products range between 5.00 and 8.00 in the 9-point hedonic scale. Most of the sensory panelists preferred cow milk kefir (p < 0.05) compared with coconut milk kefir and soy milk kefir during the sensory evaluation of all attributes. Meanwhile, the preference between coconut milk kefir and soy milk kefir was similar (p>0.05) in all attributes. Therefore, this study will be useful for probiotic manufacturers in the production of alternative probiotic drinks using dairy and non-dairy milk.

Matched MeSH terms: Bile Acids and Salts
Fulltext Bile acids and their respective conjugates elicit different responses in neonatal cardiomyocytes: role of Gi protein, muscarinic receptors and TGR5

Ibrahim E, Diakonov I, Arunthavarajah D, Swift T, Goodwin M, McIlvride S, et al.

Sci Rep, 2018 05 08;8(1):7110.
PMID: 29740092 DOI: 10.1038/s41598-018-25569-4

Bile acids are recognised as bioactive signalling molecules. While they are known to influence arrhythmia susceptibility in cholestasis, there is limited knowledge about the underlying mechanisms. To delineate mechanisms underlying fetal heart rhythm disturbances in cholestatic pregnancy, we used FRET microscopy to monitor cAMP release and contraction measurements in isolated rodent neonatal cardiomyocytes. The unconjugated bile acids CDCA, DCA and UDCA and, to a lesser extent, CA were found to be relatively potent agonists for the GPBAR1 (TGR5) receptor and elicit cAMP release, whereas all glyco- and tauro- conjugated bile acids are weak agonists. The bile acid-induced cAMP production does not lead to an increase in contraction rate, and seems to be mediated by the RI isoform of adenylate cyclase, unlike adrenaline-dependent release which is mediated by the RII isoform. In contrast, bile acids elicited slowing of neonatal cardiomyocyte contraction indicating that other signalling pathways are involved. The conjugated bile acids were found to be partial agonists of the muscarinic M2, but not sphingosin-1-phosphate-2, receptors, and act partially through the Gi pathway. Furthermore, the contraction slowing effect of unconjugated bile acids may also relate to cytotoxicity at higher concentrations.

Matched MeSH terms: Bile Acids and Salts/metabolism*
Fulltext Metabolomics analysis of herb-partitioned moxibustion treatment on rats with diarrhea-predominant irritable bowel syndrome

Lin X, Liu X, Xu J, Cheng KK, Cao J, Liu T, et al.

Chin Med, 2019;14:18.
PMID: 31080495 DOI: 10.1186/s13020-019-0240-2

Background: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, which is commonly treated with antidiarrhoeal, antispasmodics, serotonergic agents or laxative agents. These treatments provide relief for IBS symptoms but may also lead to undesired side effects. Previously, herb-partitioned moxibustion (HPM) treatment has been demonstrated to be effective in ameliorating symptoms of IBS. However, the underlying mechanism of this beneficial treatment is yet to be established. The aim of the current study was to systematically assess the metabolic alterations in response to diarrhea-predominant IBS (IBS-D) and therapeutic effect of HPM.
Methods: Proton nuclear magnetic resonance spectroscopy (1H NMR)-based metabolomics approach was used to investigate fecal and serum metabolome of rat model of IBS-D with and without HPM treatment.
Results: The current results showed that IBS-induced metabolic alterations in fecal and serum sample include higher level of threonine and UDP-glucose together with lower levels of aspartate, ornithine, leucine, isoleucine, proline, 2-hydroxy butyrate, valine, lactate, ethanol, arginine, 2-oxoisovalerate and bile acids. These altered metabolites potentially involve in impaired gut secretory immune system and intestinal inflammation, malabsorption of nutrients, and disordered metabolism of bile acids. Notably, the HPM treatment was found able to normalize the Bristol stool forms scale scores, fecal water content, plasma endotoxin level, and a number of IBS-induced metabolic changes.
Conclusions: These findings may provide useful insight into the molecular basis of IBS and mechanism of the HPM intervention.

Matched MeSH terms: Bile Acids and Salts
Fulltext Bile Acids: Physiological Activity and Perspectives of Using in Clinical and Laboratory Diagnostics

Shansky Y, Bespyatykh J

Molecules, 2022 Nov 13;27(22).
PMID: 36431930 DOI: 10.3390/molecules27227830

Bile acids play a significant role in the digestion of nutrients. In addition, bile acids perform a signaling function through their blood-circulating fraction. They regulate the activity of nuclear and membrane receptors, located in many tissues. The gut microbiota is an important factor influencing the effects of bile acids via enzymatic modification. Depending on the rate of healthy and pathogenic microbiota, a number of bile acids may support lipid and glucose homeostasis as well as shift to more toxic compounds participating in many pathological conditions. Thus, bile acids can be possible biomarkers of human pathology. However, the chemical structure of bile acids is similar and their analysis requires sensitive and specific methods of analysis. In this review, we provide information on the chemical structure and the biosynthesis of bile acids, their regulation, and their physiological role. In addition, the review describes the involvement of bile acids in various diseases of the digestive system, the approaches and challenges in the analysis of bile acids, and the prospects of their use in omics technologies.

Matched MeSH terms: Bile Acids and Salts
Effects of encapsulation on the viability of potential probiotic Lactobacillus plantarum exposed to high acidity condition and presence of bile salts

Tee WF, Nazaruddin R, Tan YN, Ayob MK

Food Sci Technol Int, 2014 Sep;20(6):399-404.
PMID: 23774606 DOI: 10.1177/1082013213488775

This study investigated the survival of encapsulated potential probiotic Lactobacillus plantarum which isolated from fermented cocoa beans. κ-Carrageenan was used to encapsulate the probiotic. Encapsulation techniques such as emulsification, freeze-drying or extrusion were adopted to encapsulate the probiotic. Freeze-drying and extrusion methods showed higher (p bile salt as evidenced by the one log colony reduction as for the non-encapsulated probiotic. Further modification of freeze-drying encapsulation technique is needed to enhance the survival of the encapsulated potential probiotic L. plantarum toward bile salt in the future.

Matched MeSH terms: Bile Acids and Salts/pharmacology*
Screening of lactobacillus strains against salmonella both isolated from malaysian free-range chicken intestine for use as probiotic

Wan Mohtar Wan Yusoff, Hutari A, Jaseem WS, Aidil Abdul Hamid

Sains Malaysiana, 2011;40:1115-1122.

A total of eight strains of Lactobacillus and two strains of Salmonella were isolated from free-range Malaysian chickens intestine. Evaluation based on in vitro studies included aggregation, co-aggregation, growth with bile salts, tolerance to acidic pH, and inhibitory activity were carried out. The isolated Lactobacillus were Lactobacillus fermentum IA, Lactobacillus fermentum IB, Lactobacillus fermentum IC, Lactobacillus fermentum ID, Lactobacillus salivarius subsp. salicinus IE, Lactobacillus salivarius subsp. salicinus IF, Lactobacillus salivarius subsp. salivarius IG, and Lactobacillus spp. IH. The corresponding isolated Salmonella were Salmonella spp. 3B21 and Salmonella spp. 1A12. The ability of aggregation and also tolerance to pH 2.5 are found in Lactobacillus fermentum ID, Lactobacillus salivarius subsp. salicinus IF, Lactobacillus salivarius subsp. salivarius IG, and Lactobacillus spp. IH. The isolate most resistance to 1% bile salts is Lactobacillus fermentum ID but observed to be weak in inhibitory activity against Salmonella spp. The best co-aggregation and strongest inhibitory activity against Salmonella spp. was observed in Lactobacillus salivarius subsp. salivarius IG. Despite being not so resistant in the presence of bile salts 0.5 and 1% (w/v), the lag time in the presence of bile salts 0.3% (w/v) of Lactobacillus salivarius subsp. salivarius IG and also for Lactobacillus spp. IH are the shortest. Based on good aggregation properties, the best co-aggregation, tolerance to acidic pH 2.5 and bile salts 0.3% (w/v) and strongest inhibitory activity against Salmonella spp., Lactobacillus salivarius subsp. salivarius IG comes out as the best candidate as probiotic for chicken.

Matched MeSH terms: Bile Acids and Salts

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