PMID: 

Appl Microbiol Biotechnol. 2020 Feb ;104(3):1243-1257. Epub 2019 Dec 18. PMID: 31853561

Abstract Title: 

Effects of a probiotic intervention on Escherichia coli and high-fat diet-induced intestinal microbiota imbalance.

Abstract: 

Obesity is often associated with intestinal microbiota imbalance and increased Gram-negative bacteria characterized by higher endotoxin levels. Therefore, a study on the joint effects of a high-fat diet and Gram-negative bacteria prechallenge might provide further information on the interactive effects of intestinal microbiota and obesity as well as the effects of a probiotic intervention on these processes. This study focused on the joint effects of a high-fat diet and Escherichia coli on mouse inflammatory cytokines, intestinal microbiota, hepatic pathological changes, and the alleviating capacity of probiotics (Lactobacillus plantarum, Bifidobacterium breve, and Lactobacillus fermentum). Our results showed that E. coli administration and the high-fat diet exacerbated the inflammatory syndrome by increasing the visceral fat content, the inflammatory cell infiltration, and intestinal microbiota disorder in mice. E. coli administration caused a decrease in short-chain fatty acids in mouse feces, and probiotics effectively improved this phenomenon. Compound probiotic intervention reduced LPS and IL-1β levels, while increased IL-10 levels in mice improved the degeneration and inflammatory infiltration of mouse liver cells. The intestinal microbiota showed great differences at 3 weeks and 6 weeks post-administration. High fat and E. coli alone or in combination caused intestinal microbiota disorder, with increased harmful bacteria, and the probiotics effectively improved the intestinal flora structure and increased the fecal short-chain fatty acid (SCFA) content. In conclusion, a high-fat diet and Gram-negative bacteria challenge exacerbated the inflammatory syndrome, which can be alleviated by compound probiotic intervention.

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PMID: 

Food Funct. 2018 May 23 ;9(5):2705-2715. PMID: 29762617

Abstract Title: 

Anticancer potential against cervix cancer (HeLa) cell line of probiotic Lactobacillus casei and Lactobacillus paracasei strains isolated from human breast milk.

Abstract: 

Lactic acid bacteria have been categorized as probiotics and play a crucial role in human health by stimulating the supply of nutrients, shaping the immune system, and preventing the colonization of pathogenic microbes. This study investigated the mechanisms for the action of three potential probiotic Lactobacillus strains: Lactobacillus casei SR1, Lactobacillus casei SR2, and Lactobacillus paracasei SR4 isolated from human breast milk. These Lactobacillus strains were identified via 16S DNA sequencing and characterized via biochemical assays including acid resistance, bile resistance, antioxidant activity, and antibiotic susceptibility. The bioactivity of the cell-free culture supernatant (CFCS) secreted by these strains on the cervix cancer (HeLa) cell line was also evaluated via cytotoxicity assay and apoptosis analysis. The mechanism of anticancer activity was also investigated via RT-qPCR and western blotting. The results demonstrated that these newly isolated Lactobacillus strains from human milk displayed noticeable probiotic characteristics such as excellent antibiotic susceptibility, outstanding antioxidant activity, and promising resistance to low pH and high concentration of bile salts. The results of the conducted bioactivity assays verified that the CFCSs had acceptable anticancer effects on cervix cancer (HeLa) cells by upregulating the expression of apoptotic genes BAX, BAD, caspase3, caspase8, and caspase9 and by downregulating the expression of the BCl-2 gene. Overall, these results indicate that the Lactobacillus strains isolated from human breast milk could be considered as a topical medication with a potential therapeutic index due to their efficacy against cervix cancer cells.

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PMID: 

Food Funct. 2015 Jul ;6(7):2257-65. PMID: 26068306

Abstract Title: 

Lactobacillus paracasei subsp. paracasei M5L induces cell cycle arrest and calreticulin translocation via the generation of reactive oxygen species in HT-29 cell apoptosis.

Abstract: 

Lactobacillus paracasei subsp. paracasei M5L (L. paracasei M5L) was isolated and co-cultured with HT-29 colon cancer cells to study its anti-colorectal cancer effects and mechanism. Using the MTT assay we found that L. paracasei M5L significantly inhibits HT-29 cell proliferation. Morphological and biochemical characteristics of apoptosis were observed and confirmed by hematoxylin and eosin (HE) staining and transmission electron microscopy (TEM). Lactobacilli could change the cell cycle distribution and induce calreticulin (CRT) translocation from the endoplasmic reticulum to the surface of the cytomembrane. We also determine that vast reactive oxygen species (ROS) were generated, while the activities of superoxide dismutase (SOD) and catalase (CAT) were noticeably diminished following L. paracasei M5L treatment. This study reveals that L. paracasei M5L induces apoptosis in HT-29 cells through ROS generation followed by CRT accompanied endoplasmic reticulum (ER) stress and S phase arrest. These results provide new insights into the possible molecular mechanism of L. paracasei M5L as a novel probiotic with the potential for further application.

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PMID: 

Nutr Cancer. 2012 ;64(7):1103-11. PMID: 23061912

Abstract Title: 

Antiproliferative and proapoptotic effects of viable or heat-killed Lactobacillus paracasei IMPC2.1 and Lactobacillus rhamnosus GG in HGC-27 gastric and DLD-1 colon cell lines.

Abstract: 

Data from literature suggest the possible use of probiotics as chemopreventive agents against colon cancer, but few investigations are available on their effects on gastric cancer proliferation. In our previous study, a specific Lactobacillus, strain L. paracasei IMPC2.1, was demonstrated to colonize the human gut and positively affect fecal bacteria and biochemical parameters. The aims of the present study were to investigate the effects of L. paracasei IMPC2.1, comparing them with those of Lactobacillus rhamnosus GG (L.GG), either as viable or heat-killed cells, on cell proliferation and apoptosis in a gastric cancer (HGC-27) and a colorectal cancer cell line (DLD-1). Both the gastric and colon cancer cells were sensitive to the growth inhibition and apoptosis induction by both viable or heat-killed cells from L. paracasei IMPC2.1 and L.GG. These findings suggest the possibility for a food supplement, based on dead probiotics, including L. paracasei IMPC2.1 cells, which could represent an effective component of a functional food strategy for cancer growth inhibition, with potential for cancer prevention.

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PMID: 

Biomed Res Int. 2018 ;2018:2871710. Epub 2018 Feb 7. PMID: 29568745

Abstract Title: 

Whole Peptidoglycan Extracts from thesubsp.M5 Strain Exert Anticancer Activity.

Abstract: 

ThesubspM5 strain exerted potential anticancer activity through the cell wall. In this study, whole peptidoglycan (WPG) was extracted from thesubspM5 strain and was evaluated for anticancer effects as well as its properties. SDS-PAGE analysis confirmed the presence of WPG with dominant bands of approximately 14.4 kDa. Further analysis revealed that the amino acids present in the WPG consisted of alanine, glycine, glutamic acid, and lysine in a molar ratio of approximately 8 : 5 : 3 : 3.5. In addition, the cell viability of HT-29 cells with WPG addition was investigated with methyl thiazolyl tetrazolium (MTT) and trypan blue exclusion (TBE) assays, and cell apoptosis was analyzed with a transmission electron microscope, flow cytometry, and semiquantitative RT-PCR. These results showed that WPG exerted cytotoxic effects on colon cancer HT-29 cells in a dose-dependent manner and upregulatedproapoptotic genes, while downregulating antiapoptotic genes. The gene expression study definitively revealed that WPG induced a mitochondria-mediated apoptotic pathway.

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PMID: 

Arch Iran Med. 2016 Nov ;19(11):779-785. PMID: 27845547

Abstract Title: 

The Study of Extracellular Protein Fractions of Probiotic Candidate Bacteria on Cancerous Cell Line.

Abstract: 

INTRODUCTION: Probiotics are live microorganisms, habituated in the human intestine, which have a beneficial effect on our health. In spite of many reports about the anticancer effect of these bacteria in in-vivo and in-vitro, their mechanisms of action are not completely understood. The goal of this study was to compare the extracellular fractions of Lactobacillus casei and L. paracasei on the anti proliferation and apoptosis induction in K562 cell line.MATERIALS AND METHODS: L. casei and L. paracasei were cultured in MRS broth medium. Then extracellular secretions were collected and after enrichment, analyzed by electrophoresis. Fractionation were determined by gel filtration chromatography using sephadex G100 column, and the anticancer properties were evaluated.RESULTS: The results of SDS-PAGE showed various molecular weight of fractionated proteins of L. casei and L. paracasei. Bioactivity assessment illustrated that anti proliferative effects on K562 cells is dose and time dependent and the cytotoxic effects was parallel with protein concentration and the increase of time from 36 to 72 hours.CONCLUSION: Regarding the cell cytotoxicity results, the fractionated extracellular proteins of L. casei and L. paracasei have significant effects in inhibition of cancer cell proliferation. However, more study is needed to better elucidate the  mechanisms of extracted proteins, and its effect on other human cancer cell lines.

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PMID: 

Lett Appl Microbiol. 2019 Sep ;69(3):148-154. Epub 2019 Jul 30. PMID: 31278768

Abstract Title: 

Potential anticancer effects of cell wall protein fractions from Lactobacillus paracasei on human intestinal Caco-2 cell line.

Abstract: 

Consumption of probiotics has an important role in colorectal cancer prevention. In this study, we aimed to explore that the cell wall protein fractions from Lactobacillus paracasei could induce apoptosis on Caco-2 cell line. The cell wall proteins from L. paracasei were fractionated by gel filtration chromatography (F1, F2 and F3) and characterized by polyacrylamide gel electrophoresis (SDS-PAGE). The anticancer properties were evaluated using MTT assay and Annexin V-FITC/PI staining. Administration of L. paracasei increased a significant concentration- and time-dependent anti-proliferative effect on Caco-2 cell line, determined by cell viability assays. However, a dramatic decrease in cell viability of Caco-2 cells was observed at the concentration of 100 µg mlof F1 L. paracasei for 72 h (58% cell viability, P 

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PMID: 

Food Sci Nutr. 2019 Aug ;7(8):2636-2646. Epub 2019 Jul 15. PMID: 31428351

Abstract Title: 

Jlus66 extenuate oxidative stress and inflammation via regulation of intestinal flora in rats with non alcoholic fatty liver disease.

Abstract: 

The nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease that affects the health of people in an increasing rate. In the current research, we investigated the beneficial effect of a novel probiotic strainJlus66 (Jlus66) on rats with high-fat diet (HFD)-induced NAFLD. The intestinal flora of rats was analyzed based on V3-V4 region 16S rDNA sequencing. Moreover, we measured the oxidative stress and inflammation factors in the liver using commercial ELISA kit, and the lipopolysaccharide (LPS) in serum with chromogenic end-point tachypheus amebocyte lysate. Compared with the HFD-induced group, Jlus66 treatment significantly decreased the malondialdehyde (MDA) level in the serum ( 

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PMID: 

Mol Nutr Food Res. 2019 Nov ;63(22):e1900457. Epub 2019 Sep 12. PMID: 31433912

Abstract Title: 

Ameliorative Effects of Probiotic Lactobacillus paracasei NL41 on Insulin Sensitivity, Oxidative Stress, and Beta-Cell Function in a Type 2 Diabetes Mellitus Rat Model.

Abstract: 

SCOPE: The present study aims to assess the antidiabetic effect of Lactobacillus paracasei strain NL41 and its potential mechanisms in rats with type 2 diabetes mellitus (T2DM) induced by a high-fat diet and low-dose streptozotocin administration (HFD/STZ).METHODS AND RESULTS: Eighteen Sprague-Dawley (SD) rats are randomly assigned to three groups: one control, one HFD/STZ model, and one HFD/STZ-Lactobacillus protection group with administration of strain NL41 for 12 weeks. Blood is collected for biochemical parameters analysis and tissue samples for histological analysis. Treatment with strain NL41 results in excellent blood glucose regulation and significantly decreases insulin resistance, and HbA1c, glucagon, and leptin levels, accompanied by remarkable improvement of dyslipidemia and oxidative stress status in the animals. Islets of Langerhans, liver, and kidney are significantly protected in the NL41-treated rats compared to the HFD/STZ-T2DM model rats. Histochemistry shows that strain NL41 inhibits beta-cell loss and alpha-cell expansion, indicating pancreatic islets as the targeted tissues for the primary ameliorative effect of the probiotic strain on HFD/STZ-T2DM rats. Crosstalk between the gut-liver and liver-pancreas endocrine axes is discussed.CONCLUSION: Probiotic strain NL41 prevents HFD/STZ-T2DM by decreasing insulin resistance and oxidative stress status, and protecting beta-cell function.

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PMID: 

Crit Rev Food Sci Nutr. 2017 May 24 ;57(8):1569-1583. PMID: 25875150

Abstract Title: 

Evidence for the effects of yogurt on gut health and obesity.

Abstract: 

Obesity is associated with increased risk for chronic diseases, and affects both developed and developing nations. Yogurt is a nutrient-dense food that may benefit individuals with lactose intolerance, constipation and diarrheal diseases, hypertension, cardiovascular diseases, diabetes, and certain types of cancer. Emerging evidence suggests that yogurt consumption might also improve the health of obese individuals. Obesity is often accompanied by chronic, low-grade inflammation perpetuated by adipose tissue and the gut. In the gut, obesity-associated dysregulation of microbiota and impaired gut barrier function may increase endotoxin exposure. Intestinal barrier function can be compromised by pathogens, inflammatory cytokines, endocannabinoids, diet, exercise, and gastrointestinal peptides. Yogurt consumption may improve gut health and reduce chronic inflammation by enhancing innate and adaptive immune responses, intestinal barrier function, lipid profiles, and by regulating appetite. While this evidence suggests that yogurt consumption is beneficial for obese individuals, randomized-controlled trials are needed to further support this hypothesis.

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