Dysbiosis in the intestinal microflora can affect the gut production of microbial metabolites,and toxic substances can disrupt the barrier function of the intestinal wall,leading to the development of various diseases...Dysbiosis in the intestinal microflora can affect the gut production of microbial metabolites,and toxic substances can disrupt the barrier function of the intestinal wall,leading to the development of various diseases.Decreased levels of Clostridium subcluster XIVa(XIVa)are associated with the intestinal dysbiosis found in inflammatory bowel disease(IBD)and Clostridium difficile infection(CDI).Since XIVa is a bacterial group responsible for the conversion of primary bile acids(BAs)to secondary BAs,the proportion of intestinal XIVa can be predicted by determining the ratio of deoxycholic acid(DCA)/[DCA+cholic acid(CA)]in feces orserum.For example,serum DCA/(DCA+CA)was significantly lower in IBD patients than in healthy controls,even in the remission period.These results suggest that a low proportion of intestinal XIVa in IBD patients might be a precondition for IBD onset but not a consequence of intestinal inflammation.Another report showed that a reduced serum DCA/(DCA+CA)ratio could predict susceptibility to CDI.Thus,the BA profile,particularly the ratio of secondary to primary BAs,can serve as a surrogate marker of the intestinal dysbiosis caused by decreased XIVa.展开更多
The anti-cancer therapy of irinotecan (CPT-11) is often limited due to severe late-onset diarrhea. Because the higher toxic form of CPT-11/its active metabolite (SN-38) is produced at acidification, the usefulness of ...The anti-cancer therapy of irinotecan (CPT-11) is often limited due to severe late-onset diarrhea. Because the higher toxic form of CPT-11/its active metabolite (SN-38) is produced at acidification, the usefulness of oral sodium bicarbonate treatment against the CPT-11/SN-38-induced intestinal injuries and diarrhea has been confirmed. However, the roles of bicarbonate have been suggested to affect not only intestinal pH environment but also intracellular pH and CPT-11/SN-38 dynamics. The present study proposed to clarify the hypothesis in CPT-11/SN-38-exposed colon cell line in various pH conditions adjusted by bicarbonate. HT29 cell pre-exposed to ~1.0 μM SN-38 lactone or carboxylate forms was incubated at different pH adjusted by either bicarbonate or HCl/NaOH. The degrees of SN-38-induced cell injury depended on the higher proportion of the toxic form (lactone) of SN-38 rather than mere pH condition of medium. Apoptosis and cell injury induced by SN-38 were significantly inhibited by bicarbonate in a dose-dependent manner. Intercellular pH acidification induced by SN-38 was significantly prevented by 30 mM bicarbonate. Cell cytotoxicity of SN-38 depended on not only extracellular but also intracellular pH that converts the SN-38 form, while the intracellular acidification was prevented by bicarbonate. The multiple regulations of bicarbonate on both exracellular and intracellular pH would be essential mechanism against intestinal cell injury by CPT-11/SN-38.展开更多
文摘Dysbiosis in the intestinal microflora can affect the gut production of microbial metabolites,and toxic substances can disrupt the barrier function of the intestinal wall,leading to the development of various diseases.Decreased levels of Clostridium subcluster XIVa(XIVa)are associated with the intestinal dysbiosis found in inflammatory bowel disease(IBD)and Clostridium difficile infection(CDI).Since XIVa is a bacterial group responsible for the conversion of primary bile acids(BAs)to secondary BAs,the proportion of intestinal XIVa can be predicted by determining the ratio of deoxycholic acid(DCA)/[DCA+cholic acid(CA)]in feces orserum.For example,serum DCA/(DCA+CA)was significantly lower in IBD patients than in healthy controls,even in the remission period.These results suggest that a low proportion of intestinal XIVa in IBD patients might be a precondition for IBD onset but not a consequence of intestinal inflammation.Another report showed that a reduced serum DCA/(DCA+CA)ratio could predict susceptibility to CDI.Thus,the BA profile,particularly the ratio of secondary to primary BAs,can serve as a surrogate marker of the intestinal dysbiosis caused by decreased XIVa.
文摘The anti-cancer therapy of irinotecan (CPT-11) is often limited due to severe late-onset diarrhea. Because the higher toxic form of CPT-11/its active metabolite (SN-38) is produced at acidification, the usefulness of oral sodium bicarbonate treatment against the CPT-11/SN-38-induced intestinal injuries and diarrhea has been confirmed. However, the roles of bicarbonate have been suggested to affect not only intestinal pH environment but also intracellular pH and CPT-11/SN-38 dynamics. The present study proposed to clarify the hypothesis in CPT-11/SN-38-exposed colon cell line in various pH conditions adjusted by bicarbonate. HT29 cell pre-exposed to ~1.0 μM SN-38 lactone or carboxylate forms was incubated at different pH adjusted by either bicarbonate or HCl/NaOH. The degrees of SN-38-induced cell injury depended on the higher proportion of the toxic form (lactone) of SN-38 rather than mere pH condition of medium. Apoptosis and cell injury induced by SN-38 were significantly inhibited by bicarbonate in a dose-dependent manner. Intercellular pH acidification induced by SN-38 was significantly prevented by 30 mM bicarbonate. Cell cytotoxicity of SN-38 depended on not only extracellular but also intracellular pH that converts the SN-38 form, while the intracellular acidification was prevented by bicarbonate. The multiple regulations of bicarbonate on both exracellular and intracellular pH would be essential mechanism against intestinal cell injury by CPT-11/SN-38.
