D-lactic acidosis: turning sugar into acids in the gastrointestinal tract.

While an appreciable quantity of organic acids is produced each day by bacterial metabolism in the gastrointestinal (GI) tract [1, 2], there is usually no acid-base consequence from this acid load because the rate of production of these acids does not exceed the capacity of the normal host to metabolize them. Nevertheless, after jejuninoileal bypass surgery or substantial small bowel resection, appreciable quantities of acids such as D-lactic acid may accumulate [3—12]. Hence the stage is set for the development of D-lactic acidosis when there is a combination of altered GI anatomy and a change in bacterial flora (such as the use of antibiotics). A less well recognized clinical association is the aggravation of the clinical picture when more glucose is supplied to these bacteria [13—16]. The extent to which production of organic acids will cause metabolic acidosis also depends on biochemical considerations. Not only must one consider whether the patient has the enzymatic machinery to metabolize each added acid, but one must also appreciate the limitations set by the overall rate of ATP turnover in cells [17] and the competition between fuels to be the substrate oxidized to regenerate the ATP needed to perform biologic work in individual cells [18]. Moreover, there is a quantitative relationship between H removal and ATP regeneration that differs between individual organic acids [19]. This manuscript is divided into two sections: first we shall discuss the normal metabolism and functions of organic acids produced in the GI tract; second, we shall consider the different types of presentation of organic acidosis where GI bacteria might have played a central role, highlighting biochemical aspects so that a more rational design for therapy can be suggested.