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Daniel Tomé - One of the best experts on this subject based on the ideXlab platform.

  • Changes in the Luminal Environment of the Colonic Epithelial Cells and Physiopathological Consequences
    American Journal of Pathology, 2017
    Co-Authors: Francois Blachier, Martin Beaumont, Mireille Andriamihaja, Anne-marie Davila, Anneig Lan, Marta Grauso, Lucie Armand, Robert Benamouzig, Daniel Tomé
    Abstract:

    Evidence, mostly from experimental models, has accumulated, indicating that modifications of Bacterial Metabolite concentrations in the large intestine Luminal content, notably after changes in the dietary composition, may have important beneficial or deleterious consequences for the colonic epithelial cell metabolism and physiology in terms of mitochondrial energy metabolism, reactive oxygen species production, gene expression, DNA integrity, proliferation, and viability. Recent data suggest that for some Bacterial Metabolites, like hydrogen sulfide and butyrate, the extent of their oxidation in colonocytes affects their capacity to modulate gene expression in these cells. Modifications of the luminal Bacterial Metabolite concentrations may, in addition, affect the colonic pH and osmolarity, which are known to affect colonocyte biology per se. Although the colonic epithelium appears able to face, up to some extent, changes in its Luminal environment, notably by developing a metabolic adaptive response, some of these modifications may likely affect the homeostatic process of colonic epithelium renewal and the epithelial barrier function. The contribution of major changes in the colonocyte luminal environment in pathological processes, like mucosaL inflammation, preneoplasia, and neoplasia, although suggested by several studies, remains to be precisely evaluated, particularly in a long-term perspective.

  • The deleterious metabolic and genotoxic effects of the Bacterial Metabolite p-cresol on colonic epithelial cells
    Free Radical Biology and Medicine, 2015
    Co-Authors: Mireille Andriamihaja, Martin Beaumont, Daniel Tomé, Annaig Lan, Marc Audebert, Ximena Wong, Kana Yamada, Yulong Yin, Catalina Carrasco-pozo, Martin Gotteland
    Abstract:

    p-Cresol that is produced by the intestinal microbiota horn the amino acid tyrosine is found at millimolar concentrations in the human feces. The effects of this Metabolite On colonic epithelial cells were tested in this study. Using the human colonic epithelial HT-29 Glc(-/+) cell line, we found that 0.8 mM p-cresol inhibits cell proliferation, an effect concomitant with an accumulation of the cells in the 5 phase and with a slight increase of cell detachment without necrotic effect. At this concentration, p-cresol inhibited oxygen consumption in HT-29 Glc(-/+) cells. In rat normal colonocytes, p-cresol also inhibited respiration. Pretreatment of HT-29 Glc(-/+) cells with 0.8 mM p-cresol for 1 day resulted in an increase of the state 3 oxygen consumption and of the cell maximal respiratory capacity with concomitant increased anion superoxide production. At higher concentrations (1.6 and 3.2 mM), p-cresol showed similar effects but additionally increased after 1 day the proton leak through the inner mitochondria! membrane, decreasing the mitochondrial bioenergetic activity. At these concentrations, p-cresol was found to be genotoxic toward HT-29 Glc(-/+) and also LS-174T intestinal cells. Lastly, a decreased ATP intracellular content was observed after 3 days treatment, p-Cresol at 0.8 mM concentration inhibits colonocyte respiration and proliferation. In response, cells can mobilize their "respiratory reserve." At higher concentrations, p-cresol pretreatment uncouples cell respiration and ATP synthesis, increases DNA damage, and finally decreases the ATP cell content. Thus, we have identified p-cresol as a metabolic troublemaker and as a genotoxic agent toward colonocytes. (C) 2015 Elsevier Inc. All rights reserved.

  • the deleterious metabolic and genotoxic effects of the Bacterial Metabolite p cresol on colonic epithelial cells
    Free Radical Biology and Medicine, 2015
    Co-Authors: Mireille Andriamihaja, Martin Beaumont, Daniel Tomé, Annaig Lan, Marc Audebert, Ximena Wong, Kana Yamada, Yulong Yin, Catalina Carrascopozo, Martin Gotteland
    Abstract:

    p-Cresol that is produced by the intestinal microbiota from the amino acid tyrosine is found at millimolar concentrations in the human feces. The effects of this Metabolite on colonic epithelial cells were tested in this study. Using the human colonic epithelial HT-29 Glc–/+ cell line, we found that 0.8 mM p-cresol inhibits cell proliferation, an effect concomitant with an accumulation of the cells in the S phase and with a slight increase of cell detachment without necrotic effect. At this concentration, p-cresol inhibited oxygen consumption in HT-29 Glc–/+ cells. In rat normal colonocytes, p-cresol also inhibited respiration. Pretreatment of HT-29 Glc–/+ cells with 0.8 mM p-cresol for 1 day resulted in an increase of the state 3 oxygen consumption and of the cell maximal respiratory capacity with concomitant increased anion superoxide production. At higher concentrations (1.6 and 3.2 mM), p-cresol showed similar effects but additionally increased after 1 day the proton leak through the inner mitochondrial membrane, decreasing the mitochondrial bioenergetic activity. At these concentrations, p-cresol was found to be genotoxic toward HT-29 Glc–/+ and also LS-174T intestinal cells. Lastly, a decreased ATP intracellular content was observed after 3 days treatment. p-Cresol at 0.8 mM concentration inhibits colonocyte respiration and proliferation. In response, cells can mobilize their “respiratory reserve.” At higher concentrations, p-cresol pretreatment uncouples cell respiration and ATP synthesis, increases DNA damage, and finally decreases the ATP cell content. Thus, we have identified p-cresol as a metabolic troublemaker and as a genotoxic agent toward colonocytes.

Jong Hwan Sung - One of the best experts on this subject based on the ideXlab platform.

  • antitumor promotional effects of a novel intestinal Bacterial Metabolite ih 901 derived from the protopanaxadiol type ginsenosides in mouse skin
    Carcinogenesis, 2004
    Co-Authors: Junwan Shin, Won Yoon Chung, Yung-jue Bang, Kwang Kyun Park, Kyung-soo Chun, Jong Hwan Sung, Young-joon Surh
    Abstract:

    Epidemiological studies have demonstrated that ginseng intake decreases the risk of cancer. Ginseng saponins (ginsenosides) have been regarded as principal components responsible for the majority of pharmacological activities exerted by ginseng. IH-901 [20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol], an intestinal Bacterial Metabolite derived from protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess antitumor effects, including inhibition of invasion, metastasis and angiogenesis and induction of tumor cell apoptosis. Tumor promotion often accompanies an elevated ornithine decarboxylase (ODC) activity, acute inflammation and induction of cyclooxygenase-2 (COX-2) activity. Here we examined the effects of IH-901 on tumor promotion and related molecular events in mouse skin in vivo. Mouse ear edema induced by the prototype tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) was repressed by IH-901 pre-treatment in a dose-dependent manner. Topical application of IH-901 onto shaven backs of female ICR mice led to the inhibition of TPA-induced expression of COX-2 and production of prostaglandin E 2 . The eukaryotic transcription factor NF-KB has been involved in intracellular signaling pathways associated with inflammation and carcinogenesis. IH-901 pre-treatment inhibited TPA-induced epidermal NF-κB DNA binding in mouse skin, which appeared to be mediated by blocking phosphorylation and subsequent degradation of IκBα. In an attempt to elucidate the molecular mechanisms by which IH-901 inactivates NF-KB, its effects on activation of upstream signaling kinases were explored. IH-901 also inhibited the activation of ERK1/2 and Akt signaling. When IH-901 was treated topically prior to TPA, expression and activity of ODC were inhibited dose-dependently. In addition, IH-901 given prior to each topical dose of TPA markedly lowered the number of papillomas in mouse skin induced by 7, 12-dimethylbenz[a]anthracene. Taken together, these findings suggest that IH-901 exerts anti-inflammatory effects by inhibiting TPA-induced COX-2 expression, which may contribute to its antitumor-promoting effects on mouse skin carcinogenesis.

  • Antitumor promotional effects of a novel intestinal Bacterial Metabolite (IH-901) derived from the protopanaxadiol-type ginsenosides in mouse skin.
    Carcinogenesis, 2004
    Co-Authors: Ji Yoon Lee, Junwan Shin, Won Yoon Chung, Yung-jue Bang, Kwang Kyun Park, Kyung-soo Chun, Jong Hwan Sung, Young-joon Surh
    Abstract:

    Epidemiological studies have demonstrated that ginseng intake decreases the risk of cancer. Ginseng saponins (ginsenosides) have been regarded as principal components responsible for the majority of pharmacological activities exerted by ginseng. IH-901 [20-O-beta-d-glucopyranosyl-20(S)-protopanaxadiol], an intestinal Bacterial Metabolite derived from protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess antitumor effects, including inhibition of invasion, metastasis and angiogenesis and induction of tumor cell apoptosis. Tumor promotion often accompanies an elevated ornithine decarboxylase (ODC) activity, acute inflammation and induction of cyclooxygenase-2 (COX-2) activity. Here we examined the effects of IH-901 on tumor promotion and related molecular events in mouse skin in vivo. Mouse ear edema induced by the prototype tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) was repressed by IH-901 pre-treatment in a dose-dependent manner. Topical application of IH-901 onto shaven backs of female ICR mice led to the inhibition of TPA-induced expression of COX-2 and production of prostaglandin E(2). The eukaryotic transcription factor NF-kappaB has been involved in intracellular signaling pathways associated with inflammation and carcinogenesis. IH-901 pre-treatment inhibited TPA-induced epidermal NF-kappaB DNA binding in mouse skin, which appeared to be mediated by blocking phosphorylation and subsequent degradation of IkappaBalpha. In an attempt to elucidate the molecular mechanisms by which IH-901 inactivates NF-kappaB, its effects on activation of upstream signaling kinases were explored. IH-901 also inhibited the activation of ERK1/2 and Akt signaling. When IH-901 was treated topically prior to TPA, expression and activity of ODC were inhibited dose-dependently. In addition, IH-901 given prior to each topical dose of TPA markedly lowered the number of papillomas in mouse skin induced by 7,12-dimethylbenz[a]anthracene. Taken together, these findings suggest that IH-901 exerts anti-inflammatory effects by inhibiting TPA-induced COX-2 expression, which may contribute to its antitumor-promoting effects on mouse skin carcinogenesis.

  • Ginseng intestinal Bacterial Metabolite IH901 as a new anti-metastatic agent
    Archives of Pharmacal Research, 1997
    Co-Authors: HIDEO HASEGAWA, Jong Hwan Sung
    Abstract:

    Anti-metastatic activities of IH901, an intestinal Bacterial metabolic derivative formed from Ginseng protopanaxadiol saponins, was determined in vitro and in vivo . Under in vitro conditions, IH901 inhibited the migration of bovine aortic endothelial cells 25 times stronger than suramin and suppressed the invasion of HT1080 human fibrosarcoma cells into reconstituted basement membrane components of Matrigel 1000 times stronger than RGDS peptide. IH901 also showed inhibitory effect on type-IV collagenase secretion from HT1080 cells and platelet aggregation. When the anti-metastatic activity of IH901 was evaluated in comparison with that of 5-FU using a spontaneous lung metastatic model of Lewis lung carcinoma, the administration of IH901 (10 mg/kg p. o.) to tumor-bearing mice led to a significant decrease in lung metastasis (43% of untreated control), which was slightly more effective than that obtained with 5-FU (56% of control). Thus, IH901 seems to exhibit its anti-metastatic activity partly through the inhibition of tumor invasion which results from the blockade of type IV collagenase secretion and also through anti-platelet and anti-angiogenic activities.

HIDEO HASEGAWA - One of the best experts on this subject based on the ideXlab platform.

  • Induction of apoptosis in Lewis lung carcinoma cells by an intestinal Bacterial Metabolite produced from orally administered ginseng protopanaxadiol saponins.
    2000
    Co-Authors: Kazuhito Suda, HIDEO HASEGAWA, Koji Murakami, Ikuo Saiki
    Abstract:

    The　present　study　demonstrated　that　oral　administration　of　an　intestinal　Bacterial　Metabolite（M1） of　protopanaxadio1－type　saponin　significantly　inhibited　the　tumor　growth　at　the　implantation　site　after intrapulmonary　implantation　of　Lewis　lung　carcinoma（LLC）cells，and　suppressed　the　metastasis　to mediastinal　lymph　nodes．We　also　investigated　the　inhibitory　mechanism　of　Ml　on　the　growth　of　LLC cells．MI　inhibitedtheproliferationofLLCcellsinaconcentration－dependentmanner，withcharacteris－ tic　morphological　changes　at　the　concentration　of30μM．Treatment　of　LLC　cells　with　MI　resulted　in marked　elevation　of　the　caspase－3activity，peaking　at2h，and　a　subsequent　time－dependent　induction of　apoptosis　during　the　period　from3to24h，as　evidencedby　DNA　fragmentation　analysis．Since　M1－ induced　growth　inhibition　of　LLC　cells　was　completely　abrogated　by　the　pretreatment　with　a　specific inhibitor　of　caspase－3，Z－DEVD－FMK，MI　fmctions　via　the　activation　of　caspase－3in　the　process　of apoptosis　in　LLC　cells．Thus，the　anti－proliferative　activity　ofMl　against　LLC　cells　is　primarily　dueto the　induction　of　apoptosis　via　promotion　of　caspase－3activity，and　this　induction　may　lead　to　the　anti－

  • antimetastatic efficacy of orally administered ginsenoside rb1 in dependence on intestinal Bacterial hydrolyzing potential and significance of treatment with an active Bacterial Metabolite
    Planta Medica, 1998
    Co-Authors: HIDEO HASEGAWA, Masamori Uchiyama
    Abstract:

    The antimetastatic effects of orally administered ginsenoside Rb 1 (Rb 1 ) and an active Metabolite by intestinal bacteria, 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (I), were studied, by using a spontaneous metastasis model produced by subcutaneous injection of Lewis lung carcinoma (LLC) in syngeneic C57BL/6 mice. A thorough analysis of the hydrolyzing potential (transformation by intestinal bacteria) was first done and the data found were positively correlated to the antimetastatic effect of Rb 1 through the medium of I. The transformation rate by 41% fecal specimens was less than 10% and consecutive Ginseng administrations were ineffective for the mice with hydrolyzing potential of less than 10%, which limited the antimetastatic efficacy of Rb 1 . In contrast, the efficacy of I was greater than that of Rb 1 and at least comparable to that of 5-FU. No effect of I on the primary tumor growth was found, indicating a specific antimetastatic activity. In a leg amputation model with the LLC-line, an effect on survival time of I (8 mg/ kg/day) equal to that of 5-FU (10 mg/kg/day) was seen and 38 % mice were cured as compared with 13 % cured by amputation alone. These findings suggest that the active drug is the Bacterial Metabolite I which should be administered rather than Rb 1 .

  • an intestinal Bacterial Metabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells
    Biochemical and Biophysical Research Communications, 1998
    Co-Authors: C Wakabayashi, HIDEO HASEGAWA, J. Murata, Koji Murakami, Ikuo Saiki
    Abstract:

    Our previous study demonstrated that thein vivoanti-metastatic effect induced by oral administration of ginseng protopanaxadiol saponins was mediated by their metabolic component M1, and that the growth, invasion and migration of tumor cells were inhibited by M1 but not by ginsenosides. Here we investigated the inhibitory mechanism of M1 on the growth of tumor cells. M1 inhibited the proliferation of B16-BL6 mouse melanoma cells in a time- and dose-dependent manner, with accompanying morphological changes at the concentration of 20 μM. In addition, at 40 μM M1 induced apoptotic cell death within 24 h. Fluorescence microscopy revealed that dansyl M1 entered the cytosol and quickly reached the nuclei (approximately 15 min). Western blot analysis revealed that M1 rapidly up-regulated the expression of p27Kip1, but down-regulated the expression of c-Myc and cyclin D1 in a time-dependent manner. Thus, the regulation of apoptosis-related proteins by M1 is responsible for the induction of apoptotic cell death, and this probably leads to the anti-metastatic activityin vivo.

  • Ginseng intestinal Bacterial Metabolite IH901 as a new anti-metastatic agent
    Archives of Pharmacal Research, 1997
    Co-Authors: HIDEO HASEGAWA, Jong Hwan Sung
    Abstract:

    Anti-metastatic activities of IH901, an intestinal Bacterial metabolic derivative formed from Ginseng protopanaxadiol saponins, was determined in vitro and in vivo . Under in vitro conditions, IH901 inhibited the migration of bovine aortic endothelial cells 25 times stronger than suramin and suppressed the invasion of HT1080 human fibrosarcoma cells into reconstituted basement membrane components of Matrigel 1000 times stronger than RGDS peptide. IH901 also showed inhibitory effect on type-IV collagenase secretion from HT1080 cells and platelet aggregation. When the anti-metastatic activity of IH901 was evaluated in comparison with that of 5-FU using a spontaneous lung metastatic model of Lewis lung carcinoma, the administration of IH901 (10 mg/kg p. o.) to tumor-bearing mice led to a significant decrease in lung metastasis (43% of untreated control), which was slightly more effective than that obtained with 5-FU (56% of control). Thus, IH901 seems to exhibit its anti-metastatic activity partly through the inhibition of tumor invasion which results from the blockade of type IV collagenase secretion and also through anti-platelet and anti-angiogenic activities.

  • in vivo antimetastatic action of ginseng protopanaxadiol saponins is based on their intestinal Bacterial Metabolites after oral administration
    Oncology Research, 1997
    Co-Authors: C Wakabayashi, HIDEO HASEGAWA, J. Murata, I. Saiki
    Abstract:

    The present study demonstrated in vivo and in vitro antimetastatic activities of a major intestinal Bacterial Metabolite Ml formed from protopanaxadiol saponins of ginseng (the root of Panax ginseng C. A. Meyer) in comparison with its whole standardized extract and ginsenosides Rb 1 , Rb 2 , and R c . Although Ginseng extract (I mg/mouse) and ginsenosides (0.5 mg/mouse) significantly inhibited lung metastasis produced by IV injection of B16-BL6 melanoma cells in syngeneic mice (27-61% of untreated control), they hardly inhibited the invasion and migration of B16-BL6 melanoma and HT1080 fibrosarcoma cells in vitro. However, the intestinal Bacterial Metabolite Ml inhibited lung metastasis of melanoma cells and in vitro tumor cell invasion and migration at nontoxic or marginally toxic concentrations. Additionally, pharmacokinetic studies of ginsenoside Rb 1 and M1 after oral administration (2 mg/mouse) revealed that intact Rb 1 was not detectable in serum for 24 h by HPLC analysis, whereas the level of M1 in the serum reached maximum at 8 h (8.5 + 0.4 μg/ml) after Rb 1 administration and at 2 h (10.3 ± 1.0 μg/ ml) after M1 administration. These findings suggest that the in vivo antimetastatic effect by oral administration of ginsenosides is mediated by their metabolic component M1.

Francois Blachier - One of the best experts on this subject based on the ideXlab platform.

  • Dietary proline supplementation alters colonic luminal microbiota and Bacterial Metabolite composition between days 45 and 70 of pregnancy in Huanjiang mini-pigs.
    Journal of Animal Science and Biotechnology, 2018
    Co-Authors: Qiuping Guo, Francois Blachier, Yulong Yin, Xiang-feng Kong
    Abstract:

    Pregnancy is associated with important changes in gut microbiota composition. Dietary factors may affect the diversity, composition, and metabolic activity of the intestinal microbiota. Among amino acids, proline is known to play important roles in protein metabolism and structure, cell differentiation, conceptus growth and development, and gut microbiota re-equilibration in case of dysbiosis. Dietary supplementation with 1% proline decreased (P 

  • dietary proline supplementation alters colonic luminal microbiota and Bacterial Metabolite composition between days 45 and 70 of pregnancy in huanjiang mini pigs
    Journal of animal science and biotechnology, 2018
    Co-Authors: Qiuping Guo, Francois Blachier, Yulong Yin, Xiang-feng Kong
    Abstract:

    Pregnancy is associated with important changes in gut microbiota composition. Dietary factors may affect the diversity, composition, and metabolic activity of the intestinal microbiota. Among amino acids, proline is known to play important roles in protein metabolism and structure, cell differentiation, conceptus growth and development, and gut microbiota re-equilibration in case of dysbiosis. Dietary supplementation with 1% proline decreased (P < 0.05) the amounts of Klebsiella pneumoniae, Peptostreptococcus productus, Pseudomonas, and Veillonella spp. in distal colonic contents than that in the control group. The colonic contents of Butyrivibrio fibrisolvens, Bifidobacterium sp., Clostridium coccoides, Clostridium coccoides-Eubacterium rectale, Clostridium leptum subgroup, Escherichia coli, Faecalibacterium prausnitzii, Fusobacterium prausnitzii, and Prevotella increased (P < 0.05) on d 70 of pregnancy as compared with those on d 45 of pregnancy. The colonic concentrations of acetate, total straight-chain fatty acid, and total short-chain fatty acids (SCFA) in the proline-supplemented group were lower (P < 0.05), and butyrate level (P = 0.06) decreased as compared with the control group. Almost all of the SCFA displayed higher (P < 0.05) concentrations in proximal colonic contents on d 70 of pregnancy than those on d 45 of pregnancy. The concentrations of 1,7-heptyl diamine (P = 0.09) and phenylethylamine (P < 0.05) in proximal colonic contents were higher, while those of spermidine (P = 0.05) and total bioamine (P = 0.06) tended to be lower in the proline-supplemented group than those in the control group. The concentrations of spermidine, spermine, and total bioamine in colonic contents were higher (P < 0.05) on d 70 of pregnancy than those measured on d 45 of pregnancy. In contrast, the concentration of phenylethylamine was lower (P < 0.05) on d 70 than on d 45 of pregnancy. These findings indicate that L-proline supplementation modifies both the colonic microbiota composition and the luminal concentrations of several Bacterial Metabolites. Furthermore, our data show that both the microbiota composition and the concentrations of Bacterial Metabolites are evolving in the course of pregnancy. These results are discussed in terms of possible implication in terms of luminal environment and consequences for gut physiology and health.

  • Colon epithelial cells luminal environment and physiopathological consequences: impact of nutrition and exercise
    Nutrire, 2018
    Co-Authors: Francois Blachier, Ayane De Sá Resende, Geovana Da Silva Fogaça Leite, Aline Vasques Da Costa, Antonio Herbert Lancha Junior
    Abstract:

    The colonic epithelial cells represent a border between the colon luminal content, containing notably bacteria and a complex mixture of compounds, and the “milieu interieur” as defined by the French physiologist Claude Bernard. The physical-chemical composition of the luminal content, including luminal pH and Bacterial Metabolite, that obviously is not constant, is modified for instance according to the diet. Data obtained recently indicate that physical exercise may also modify the colonic luminal content. Evidence has indicated that modification of the luminal content characteristics has, indeed, consequences for the colonic epithelial cells, notably in terms of energy metabolism and DNA integrity. Although such alterations impact presumably the homeostatic process of the colonic epithelium renewal and the epithelial barrier function, their contribution to pathological processes like mucosal inflammation, pre-neoplasia, and neoplasia remains partly elusive. Open questions remain regarding the individual and collective roles of luminal changes, particularly in a long-term perspective. These questions are related particularly to the capacity of the Bacterial Metabolites to cross the mucus layer before entering the colonocytes, to the concentrations of Metabolites in proximity of the colonic crypt stem cells, and to the capacity of colonocytes to detoxicate deleterious compounds, to take up and utilize beneficial compounds.

  • Dietary proline supplementation alters colonic luminal microbiota and Bacterial Metabolite composition between days 45 and 70 of pregnancy in Huanjiang mini-pigs
    Journal of Animal Science and Biotechnology, 2018
    Co-Authors: Qiuping Guo, Francois Blachier, Yulong Yin, Xiang-feng Kong
    Abstract:

    Background: Pregnancy is associated with important changes in gut microbiota composition. Dietary factors may affect the diversity, composition, and metabolic activity of the intestinal microbiota. Among amino acids, proline is known to play important roles in protein metabolism and structure, cell differentiation, conceptus growth and development, and gut microbiota re-equilibration in case of dysbiosis. Results: Dietary supplementation with 1% proline decreased (P < 0.05) the amounts of Klebsiella pneumoniae, Peptostreptococcus productus, Pseudomonas, and Veillonella spp. in distal colonic contents than that in the control group. The colonic contents of Butyrivibrio fibrisolvens, Bifidobacterium sp., Clostridium coccoides, Clostridium coccoides-Eubacterium rectale, Clostridium leptum subgroup, Escherichia coli, Faecalibacterium prausnitzii, Fusobacterium prausnitzii, and Prevotella increased (P < 0.05) on d 70 of pregnancy as compared with those on d 45 of pregnancy. The colonic concentrations of acetate, total straight-chain fatty acid, and total short-chain fatty acids (SCFA) in the proline-supplemented group were lower (P < 0.05), and butyrate level (P = 0.06) decreased as compared with the control group. Almost all of the SCFA displayed higher (P < 0.05) concentrations in proximal colonic contents on d 70 of pregnancy than those on d 45 of pregnancy. The concentrations of 1,7-heptyl diamine (P = 0.09) and phenylethylamine (P < 0.05) in proximal colonic contents were higher, while those of spermidine (P = 0.05) and total bioamine (P = 0.06) tended to be lower in the proline-supplemented group than those in the control group. The concentrations of spermidine, spermine, and total bioamine in colonic contents were higher (P < 0.05) on d 70 of pregnancy than those measured on d 45 of pregnancy. In contrast, the concentration of phenylethylamine was lower (P < 0.05) on d 70 than on d 45 of pregnancy. Conclusion: These findings indicate that L-proline supplementation modifies both the colonic microbiota composition and the luminal concentrations of several Bacterial Metabolites. Furthermore, our data show that both the microbiota composition and the concentrations of Bacterial Metabolites are evolving in the course of pregnancy. These results are discussed in terms of possible implication in terms of luminal environment and consequences for gut physiology and health.

  • Changes in the Luminal Environment of the Colonic Epithelial Cells and Physiopathological Consequences
    American Journal of Pathology, 2017
    Co-Authors: Francois Blachier, Martin Beaumont, Mireille Andriamihaja, Anne-marie Davila, Anneig Lan, Marta Grauso, Lucie Armand, Robert Benamouzig, Daniel Tomé
    Abstract:

    Evidence, mostly from experimental models, has accumulated, indicating that modifications of Bacterial Metabolite concentrations in the large intestine Luminal content, notably after changes in the dietary composition, may have important beneficial or deleterious consequences for the colonic epithelial cell metabolism and physiology in terms of mitochondrial energy metabolism, reactive oxygen species production, gene expression, DNA integrity, proliferation, and viability. Recent data suggest that for some Bacterial Metabolites, like hydrogen sulfide and butyrate, the extent of their oxidation in colonocytes affects their capacity to modulate gene expression in these cells. Modifications of the luminal Bacterial Metabolite concentrations may, in addition, affect the colonic pH and osmolarity, which are known to affect colonocyte biology per se. Although the colonic epithelium appears able to face, up to some extent, changes in its Luminal environment, notably by developing a metabolic adaptive response, some of these modifications may likely affect the homeostatic process of colonic epithelium renewal and the epithelial barrier function. The contribution of major changes in the colonocyte luminal environment in pathological processes, like mucosaL inflammation, preneoplasia, and neoplasia, although suggested by several studies, remains to be precisely evaluated, particularly in a long-term perspective.

Young-joon Surh - One of the best experts on this subject based on the ideXlab platform.

  • antitumor promotional effects of a novel intestinal Bacterial Metabolite ih 901 derived from the protopanaxadiol type ginsenosides in mouse skin
    Carcinogenesis, 2004
    Co-Authors: Junwan Shin, Won Yoon Chung, Yung-jue Bang, Kwang Kyun Park, Kyung-soo Chun, Jong Hwan Sung, Young-joon Surh
    Abstract:

    Epidemiological studies have demonstrated that ginseng intake decreases the risk of cancer. Ginseng saponins (ginsenosides) have been regarded as principal components responsible for the majority of pharmacological activities exerted by ginseng. IH-901 [20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol], an intestinal Bacterial Metabolite derived from protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess antitumor effects, including inhibition of invasion, metastasis and angiogenesis and induction of tumor cell apoptosis. Tumor promotion often accompanies an elevated ornithine decarboxylase (ODC) activity, acute inflammation and induction of cyclooxygenase-2 (COX-2) activity. Here we examined the effects of IH-901 on tumor promotion and related molecular events in mouse skin in vivo. Mouse ear edema induced by the prototype tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) was repressed by IH-901 pre-treatment in a dose-dependent manner. Topical application of IH-901 onto shaven backs of female ICR mice led to the inhibition of TPA-induced expression of COX-2 and production of prostaglandin E 2 . The eukaryotic transcription factor NF-KB has been involved in intracellular signaling pathways associated with inflammation and carcinogenesis. IH-901 pre-treatment inhibited TPA-induced epidermal NF-κB DNA binding in mouse skin, which appeared to be mediated by blocking phosphorylation and subsequent degradation of IκBα. In an attempt to elucidate the molecular mechanisms by which IH-901 inactivates NF-KB, its effects on activation of upstream signaling kinases were explored. IH-901 also inhibited the activation of ERK1/2 and Akt signaling. When IH-901 was treated topically prior to TPA, expression and activity of ODC were inhibited dose-dependently. In addition, IH-901 given prior to each topical dose of TPA markedly lowered the number of papillomas in mouse skin induced by 7, 12-dimethylbenz[a]anthracene. Taken together, these findings suggest that IH-901 exerts anti-inflammatory effects by inhibiting TPA-induced COX-2 expression, which may contribute to its antitumor-promoting effects on mouse skin carcinogenesis.

  • Antitumor promotional effects of a novel intestinal Bacterial Metabolite (IH-901) derived from the protopanaxadiol-type ginsenosides in mouse skin.
    Carcinogenesis, 2004
    Co-Authors: Ji Yoon Lee, Junwan Shin, Won Yoon Chung, Yung-jue Bang, Kwang Kyun Park, Kyung-soo Chun, Jong Hwan Sung, Young-joon Surh
    Abstract:

    Epidemiological studies have demonstrated that ginseng intake decreases the risk of cancer. Ginseng saponins (ginsenosides) have been regarded as principal components responsible for the majority of pharmacological activities exerted by ginseng. IH-901 [20-O-beta-d-glucopyranosyl-20(S)-protopanaxadiol], an intestinal Bacterial Metabolite derived from protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess antitumor effects, including inhibition of invasion, metastasis and angiogenesis and induction of tumor cell apoptosis. Tumor promotion often accompanies an elevated ornithine decarboxylase (ODC) activity, acute inflammation and induction of cyclooxygenase-2 (COX-2) activity. Here we examined the effects of IH-901 on tumor promotion and related molecular events in mouse skin in vivo. Mouse ear edema induced by the prototype tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) was repressed by IH-901 pre-treatment in a dose-dependent manner. Topical application of IH-901 onto shaven backs of female ICR mice led to the inhibition of TPA-induced expression of COX-2 and production of prostaglandin E(2). The eukaryotic transcription factor NF-kappaB has been involved in intracellular signaling pathways associated with inflammation and carcinogenesis. IH-901 pre-treatment inhibited TPA-induced epidermal NF-kappaB DNA binding in mouse skin, which appeared to be mediated by blocking phosphorylation and subsequent degradation of IkappaBalpha. In an attempt to elucidate the molecular mechanisms by which IH-901 inactivates NF-kappaB, its effects on activation of upstream signaling kinases were explored. IH-901 also inhibited the activation of ERK1/2 and Akt signaling. When IH-901 was treated topically prior to TPA, expression and activity of ODC were inhibited dose-dependently. In addition, IH-901 given prior to each topical dose of TPA markedly lowered the number of papillomas in mouse skin induced by 7,12-dimethylbenz[a]anthracene. Taken together, these findings suggest that IH-901 exerts anti-inflammatory effects by inhibiting TPA-induced COX-2 expression, which may contribute to its antitumor-promoting effects on mouse skin carcinogenesis.