Colonic lactate metabolism andd-lactic acidosis

Abstract

D-Lactic acidosis is seen in patients with intestinal bypass or short bowels in whom colonic produced D-lactate accumulates. An intestinal bypassed patient with D-lactic acidosis had higher fecal D-lactate (122.4 mmol/liter) and L-lactate (90.1 mmol/liter) than described before in humans. D-Lactate fluctuated between 0.5 and 3.1 mmol/liter in plasma (normal < 0.1 mmol/liter) and between 1.1 and 52.8 mmol/liter in urine (normal < 0.7 mmol/liter) within a few hours, indicating that the human organism do metabolize and excrete D-lactate. The patient with D-lactic acidosis had a 10-fold increased DL-lactate production from glucose in fecal homogenates compared to 14 healthy controls and a patient with intestinal bypass, who did not have D-lactic acidosis. A 67% carbohydrate (starch)-enriched diet resulted in a minor elevation of fecal and plasma lactate, whereas 50 + 100 + 150 g of ingested lactose increased D-lactate in feces (84.0 mmol/liter) and plasma (2.3 mmol/liter) considerably in the patient with D-lactic acidosis. Intestinal prolongation (22 cm ileum) had a temporary effect on fecal and plasma D-lactate, but intestinal continuity was reestablished 26 months later because D-lactic acidosis recurred (plasma 8.6 mmol/liter, urine 101.3 mmol/liter). Large amounts of lactulose (160 g/day) to 12 normal individuals increased D-lactate to 13.6 +/- 3.5 mmol/liter in feces, but never increased D-lactate in plasma or urine. The in vitro fermentation of glucose in fecal homogenates increased DL-lactate, which disappeared after complete metabolization of the glucose. L-Lactate was converted to D-lactate and vice versa, and both were degraded to the short-chain fatty acids acetate, propionate, and butyrate. An infrequent, but elevated ability of the colonic flora to produce lactate may be a prerequisite for D-lactic acidosis to occur and may explain why the syndrome is so seldom seen even in patients with intestinal bypass or short bowels. The suggestion that D-lactate is not metabolized and hence accumulates is probably not valid.

Impact of the Metabolic Activity of Streptococcus thermophilus on the Colon Epithelium of Gnotobiotic Rats

“…Our observation is in accord with pre- vious reports suggesting that monocarboxylic acid transporters provide a link between bacteria and the host (47)(48)(49). In human healthy adults, no or low (0 -2 mM) lactate is detected in fecal samples (50,51) because the luminal lactate is absorbed by host and is also used as an energy source by other commensal bacteria (52)(53)(54). However, increased fecal lactate has been associated with intestinal malabsorption and colitis (55).…”

Addition of a Gastrointestinal Microbiome Modulator to Metformin Improves Metformin Tolerance and Fasting Glucose Levels

“…Additional colonic contributions of d-lactate are from organisms such as Lactobacillus species, Streptococcus bovis, Bifidobacterium species, and Eubacterium species that utilize sugars present in the colon. 15,16 Furthermore, d-lactate can convert to l-lactate by some colon microbiota, which could contribute to the plasma lactate pool. 16 Bile acids are well known to promote colonic fluid and electrolyte secretion, thereby causing diarrhea associated with bile acid malabsorption.…”

“…15,16 Furthermore, d-lactate can convert to l-lactate by some colon microbiota, which could contribute to the plasma lactate pool. 16 Bile acids are well known to promote colonic fluid and electrolyte secretion, thereby causing diarrhea associated with bile acid malabsorption. 17 Metformin may cause GI disturbances by reducing ileal bile salt reabsorption leading to elevated colonic bile salt concentrations.…”

Lactic acidosis: an update

“…L-LDH is the only form of the enzyme present in mammals; many carbohydratefermenting bacteria, including Lactobacillus sp. and Bifidobacterium sp., possess both forms of the enzyme and are able to produce both stereoisomers in varying proportions [86].…”