Gastrointestinal organic acid production and metabolism

胃肠道有机酸的产生和代谢

• 批准号: 138042-2007
• 负责人: Zello, GordonAlexander
• 金额: $ 1.42万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Group
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=361887
• 关键词: Gastrointestinal; organic; acid; production; metabolism

Diarrhea causes significant illness and death, especially in young animals and children. Two complications of diarrhea are dehydration and metabolic acidosis. Metabolic acidosis causes problems when blood pH decreases below the range at which the body functions best, and various problems including death can result. The development of acidosis in diarrhea is not well understood.  We have recently shown that an acid, D-lactate, is present in the blood at high levels and contributes to acidosis in diarrheic calves. This acid is produced only by bacteria in the gut.  In diarrheic calves, injury to the gut results in D-lactate passing into the blood causing the harmful acidosis.  We believe a similar mechanism occurs in many other species, including humans.   Our objectives for this grant cycle are: 1) To determine the presence of D-lactate and D-lactic acidosis, in species other than the calf, in both healthy and diseased conditions, 2) to determine whether additional compounds contribute to the acidosis present in severe diarrhea, 3) to determine the effect of acidosis on brain and kidney function, 4) to evaluate the current therapies used in reversing acidosis, and 5) to treat D-lactic acidosis by feeding bacteria (probiotics) that do not produce D-lactate or compounds (prebiotics) which help in decreasing the production of D-lactate, as alternatives to antibiotic therapy.  This research will help further our understanding of metabolic acidosis, especially D-lactic acidosis, in diarrhea, which is both a cause of great economic loss in the agricultural industry in Canada and a disease that afflicts many children worldwide.

腹泻会导致严重的疾病和死亡，特别是在年幼的动物和儿童中。腹泻的两个并发症是脱水和代谢性酸中毒。当血液pH值降低到身体功能最佳的范围以下时，代谢性酸中毒会引起问题，并可能导致包括死亡在内的各种问题。腹泻时酸中毒的发生还不清楚，我们最近发现，血液中存在一种高水平的D-乳酸酸，它会导致腹泻小牛的酸中毒。这种酸只由肠道中的细菌产生。在消化不良的小牛中，肠道损伤导致D-乳酸盐进入血液，导致有害的酸中毒。我们相信类似的机制发生在许多其他物种中，包括人类。 我们在这个赠款周期的目标是：1）确定在健康和患病条件下，小牛以外的物种中是否存在D-乳酸盐和D-乳酸酸中毒，2）确定其他化合物是否导致严重腹泻中存在的酸中毒，3）确定酸中毒对脑和肾功能的影响，4）评价目前用于逆转酸中毒的疗法，（5）通过喂菌治疗D-乳酸酸中毒（益生菌）不产生D-乳酸盐或化合物（益生元），这有助于减少生产的D-乳酸，作为替代抗生素治疗。这项研究将有助于进一步了解代谢性酸中毒，特别是D-乳酸酸中毒，在腹泻，这既是加拿大农业中巨大经济损失的原因，也是折磨世界各地许多儿童的疾病。