D-lactic Acidosis Research Articles

P145 D-Lactic acidosis in children with short bowel syndrome: comparison between children who underwent or not lengthening surgery

P145 D-Lactic acidosis in children with short bowel syndrome: comparison between children who underwent or not lengthening surgery

The Gut Microbiome in Patients with Intestinal Failure: Current Evidence and Implications for Clinical Practice.

Intestinal failure (IF) is the reduction of gut function or mass below a minimum needed to absorb nutrients and fluids, such that patients are dependent on parenteral nutrition (PN). Patients with IF have an altered gut microbiome. Our aim was to review and evaluate the current evidence on gut microbiome and its metabolic activity, as well as its association with disease characteristics in adults and children with IF. We performed a PubMed literature search for articles published after 2000 using the following terms: intestinal, microbiome, microbiota, short-chain fatty acids, short bowel syndrome, and PN. Literature search was restricted to human studies only. The gut microbiome diversity is remarkably reduced, and community structure is altered with a noticeable overabundance of Proteobacteria, especially the Enterobacteriaceae family. A substantial increase in Lactobacillus level is often reported in patients with IF. Gut microbiome characteristics have been associated with poor growth, liver disease, D-lactic acidosis, and duration of intestinal adaptation. Differences in microbiome characteristics have been found between patients receiving PN and those whose guts have adapted and have been weaned off PN. Future research with prospective sample collection should explore the value of the gut microbiome as a biomarker to guide clinical practice and as a modifiable therapeutic target to optimize outcomes of patients with IF.

Brain fogginess, gas and bloating: a link between SIBO, probiotics and metabolic acidosis.

BackgroundD-lactic acidosis is characterized by brain fogginess (BF) and elevated D-lactate and occurs in short bowel syndrome. Whether it occurs in patients with an intact gut and unexplained gas and bloating is unknown. We aimed to determine if BF, gas and bloating is associated with D-lactic acidosis and small intestinal bacterial overgrowth (SIBO).MethodsPatients with gas, bloating, BF, intact gut, and negative endoscopic and radiological tests, and those without BF were evaluated. SIBO was assessed with glucose breath test (GBT) and duodenal aspiration/culture. Metabolic assessments included urinary D-lactic acid and rblood L-lactic acid, and ammonia levels. Bowel symptoms, and gastrointestinal transit were assessed.ResultsThirty patients with BF and 8 without BF were evaluated. Abdominal bloating, pain, distension and gas were the most severe symptoms and their prevalence was similar between groups. In BF group, all consumed probiotics. SIBO was more prevalent in BF than non-BF group (68 vs. 28%, p = 0.05). D-lactic acidosis was more prevalent in BF compared to non-BF group (77 vs. 25%, p = 0.006). BF was reproduced in 20/30 (66%) patients. Gastrointestinal transit was slow in 10/30 (33%) patients with BF and 2/8 (25%) without. Other metabolic tests were unremarkable. After discontinuation of probiotics and a course of antibiotics, BF resolved and gastrointestinal symptoms improved significantly (p = 0.005) in 23/30 (77%).ConclusionsWe describe a syndrome of BF, gas and bloating, possibly related to probiotic use, SIBO, and D-lactic acidosis in a cohort without short bowel. Patients with BF exhibited higher prevalence of SIBO and D-lactic acidosis. Symptoms improved with antibiotics and stopping probiotics. Clinicians should recognize and treat this condition.

Rapid review shows that probiotics and fermented infant formulas do not cause d-lactic acidosis in healthy children.

Extensive ongoing research on probiotics and infant formulas raises a number of safety questions. One concern is the potential influence of d-lactic acid-containing preparations on the health of infants and children. The aim of this review was to summarise the available knowledge on the ingestion of d-lactic acid-producing bacteria, acidified infant formulas and fermented infant formulas as a potential cause of paediatric d-lactic acidosis. A Medline database search was performed in July 2017, with no restrictions on the language, article type or publication date. The 1715 search results were screened for clinical trials, review articles, case series and case reports of relevance to the topic. We identified five randomised controlled trials from 2005 to 2017 covering 544 healthy infants and some case reports and experimental studies. No clinically relevant adverse effects of d-lactic acid-producing probiotics and fermented infant formulas were described in healthy children. However, a harmless, subclinical accumulation of d-lactate was theoretically possible. The only known cases of paediatric d-lactic acidosis occurred in patients with short bowel syndrome or, historically, in infants fed with acidified formulas. Our main finding was that probiotics and fermented formulas did not cause d-lactic acidosis in healthy children.

Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons

BackgroundPreliminary evidence suggests that the enteric microbiota may play a role in the expression of neurological symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Overlapping symptoms with the acute presentation of d-lactic acidosis has prompted the use of antibiotic treatment to target the overgrowth of species within the Streptococcus genus found in commensal enteric microbiota as a possible treatment for neurological symptoms in ME/CFS.MethodsAn open-label, repeated measures design was used to examine treatment efficacy and enable sex comparisons. Participants included 44 adult ME/CFS patients (27 females) from one specialist medical clinic with Streptococcus viable counts above 3.00 × 105 cfu/g (wet weight of faeces) and with a count greater than 5% of the total count of aerobic microorganisms. The 4-week treatment protocol included alternate weeks of Erythromycin (400 mg of erythromycin as ethyl succinate salt) twice daily and probiotic (d-lactate free multistrain probiotic, 5 × 1010 cfu twice daily). 2 × 2 repeated measures ANOVAs were used to assess sex-time interactions and effects across pre- and post-intervention for microbial, lactate and clinical outcomes. Ancillary non-parametric correlations were conducted to examine interactions between change in microbiota and clinical outcomes.ResultsLarge treatment effects were observed for the intention-to-treat sample with a reduction in Streptococcus viable count and improvement on several clinical outcomes including total symptoms, some sleep (less awakenings, greater efficiency and quality) and cognitive symptoms (attention, processing speed, cognitive flexibility, story memory and verbal fluency). Mood, fatigue and urine d:l lactate ratio remained similar across time. Ancillary results infer that shifts in microbiota were associated with more of the variance in clinical changes for males compared with females.ConclusionsResults support the notion that specific microorganisms interact with some ME/CFS symptoms and offer promise for the therapeutic potential of targeting gut dysbiosis in this population. Streptococcus spp. are not the primary or sole producers of d-lactate. Further investigation of lactate concentrations are needed to elucidate any role of d-lactate in this population. Concurrent microbial shifts that may be associated with clinical improvement (i.e., increased Bacteroides and Bifidobacterium or decreased Clostridium in males) invite enquiry into alternative strategies for individualised treatment.Trial Registration Australian and New Zealand Clinical Trial Registry (ACTRN12614001077651) 9th October 2014. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366933&isReview=true

D-lactic acidosis in humans: systematic literature review.

D-lactic acidosis is an uncommon and challenging form of metabolic acidosis that may develop in short bowel syndrome. It has been documented exclusively in case reports and small case series. We performed a review of the literature in the National Library of Medicine and Excerpta Medica databases. We identified 84 original reports published between 1977 and 2017. D-lactic acidosis was observed in 98 individuals ranging in age from 7months to 86years with short bowel syndrome. The clinical presentation included Kussmaul breathing, confusion, slurred speech, and gait disturbances. Furthermore, among 99 consecutive patients with short bowel syndrome, 21 reported having episodes with symptoms consistent with D-lactic acidosis. In addition, D-lactic acid might also contribute to acidosis in diabetes mellitus. Finally, abnormally high D-lactic acid was documented after administration or ingestion of large amounts of propylene glycol, as paraneoplastic phenomenon and perhaps also in a so far poorly characterized inherited inborn error of metabolism. In humans with short bowel syndrome (or carbohydrate malabsorption), D-lactic acidosis is likely rather common and under-recognized. This condition should be included in the differential diagnosis of unexplained high-gap metabolic acidosis where the anion causing the acidosis is not known. Furthermore, diabetic acidosis might be caused by accumulation of both ketone bodies and D-lactic acid. Finally, there are endogenous sources of D-lactic acid in subjects with propylene glycol intoxication.

Neurological disease in ruminants

Working up a neurological case in farm animals is not always an easy task. One of the most useful skills is a sound understanding of the principles of characterising the...

D-lactic acidosis in children with short bowel syndrome who underwent autologous bowel reconstruction: A retrospective study

Introduction: d-lactic acidosis (DLA) is an uncommon complication in children with Short Bowel Syndrome (SBS) with intestinal dilation. This condition is related to excess of production of d-lactate by intestinal bacteria when carbohydrates (CHO) are not completely absorbed in the small bowel. Our aim is to evaluate the DLA incidence in SBS children referred to our unit.

D-lactic Acidosis in Children with Short Bowel Syndrome

D-lactic Acidosis in Children with Short Bowel Syndrome

Fermentation characteristics of Megasphaera elsdenii J6 derived from pig feces on different lactate isomers

D-Lactate-utilizing bacteria play important roles in maintaining the balance of gut lactate; however, studies on gut D-lactate-utilizing bacteria have been limited. This study aimed to isolate and identify D-lactate-utilizing bacteria from pig gut using the Hungate roll-tube method, and to investigate their metabolic characteristics in vitro. Six different anaerobes were isolated from pig feces, which were identified as related to Bacteroides fragilis, Bacteroides acidifaciens, Veillonella denticariosi, Veillonella caviae, Bacteroides uniformis, and Megasphaera elsdenii based on the 16S rRNA gene sequences. All strains had a significant ability to utilize D-lactate, which was concluded after in vitro fermentation with 25 mmol L−1 D-lactate as the primary carbon source. Of all 6 strains, M. elsdenii J6 showed the highest efficiency of D-lactate utilization and produced a higher ratio of butyrate in total short chain fatty acids (SCFAs). Thus, the in vitro fermentation characteristics of this strain in D-, L-, and DL-lactate mixtures (D-lactate:L-lactate=1:1 or 1:2) were further studied. The results showed that M. elsdenii J6 preferred utilizing D-lactate, and produced more SCFA when using D-lactate as the primary carbon source. The findings suggest that the administration of D-lactate-utilizing bacteria such as M. elsdenii J6 may have a potential advantage in the alleviation of D-lactic acidosis in the animal gut.

Fecal Transplantation Successfully Treats Recurrent D‐Lactic Acidosis in a Child With Short Bowel Syndrome

D-lactic acidosis can occur in patients with short bowel syndrome (SBS) when excessive malabsorbed carbohydrate (CHO) enters the colon and is metabolized by colonic bacteria to D-lactate. D-lactate can be absorbed systemically, and increased serum levels are associated with central nervous system toxicity manifested by confusion, ataxia, and slurred speech. Current therapy, usually directed toward suppressing intestinal bacterial overgrowth and limiting ingested CHO, is not always successful. Fecal transplantation, the infusion of donor feces into a recipient's intestinal tract, has been used for decades to treat recurrent Clostridium difficile infection, and case reports document its use in the successful treatment of constipation, diarrhea, and abdominal pain. The exact mechanism of action is unknown, but it is surmised that the alteration of the intestinal microbiome, as well as the reintroduction of potential beneficial microbes, helps mediate disease. Here we present the case of a child with SBS and recurrent, debilitating D-lactic acidosis, which was successfully treated with fecal transplantation.

D-Lactic Acidosis Triggered by a Carbohydrate Load in a Patient With Crohnʼs Disease

D-Lactic Acidosis Triggered by a Carbohydrate Load in a Patient With Crohnʼs Disease

D-lactic acidosis: an underrecognized complication of short bowel syndrome.

D-lactic acidosis or D-lactate encephalopathy is a rare condition that occurs primarily in individuals who have a history of short bowel syndrome. The unabsorbed carbohydrates act as a substrate for colonic bacteria to form D-lactic acid among other organic acids. The acidic pH generated as a result of D-lactate production further propagates production of D-lactic acid, hence giving rise to a vicious cycle. D-lactic acid accumulation in the blood can cause neurologic symptoms such as delirium, ataxia, and slurred speech. Diagnosis is made by a combination of clinical and laboratory data including special assays for D-lactate. Treatment includes correcting the acidosis and decreasing substrate for D-lactate such as carbohydrates in meals. In addition, antibiotics can be used to clear colonic flora. Although newer techniques for diagnosis and treatment are being developed, clinical diagnosis still holds paramount importance, as there can be many confounders in the diagnosis as will be discussed subsequently.

D-lactic acidosis mediated neuronal encephalopathy in acute lymphoblastic leukemia patient: An under diagnosis

BackgroundD-lactic acidosis, also referred as D-lactate encephalopathy, has been reported in patients with short bowl syndrome (SBS). Case reportThe neurologic symptoms include altered mental status, slurred speech, and ataxia. Onset of neurological symptoms is accompanied by metabolic acidosis and high anion gap. We present here a case of D-lactic acidosis in a patient with acute lymphoblastic leukemia (ALL) who developed severe neurological symptoms and metabolic acidosis due to vancomycin-resistant enterococci (VRE) infection, and elevated D-lactic acid.

Duodenal lengthening in short bowel with dilated duodenum

Although duodenal dilatation occurs in children with short bowel syndrome (SBS) facilitating dismotility and bacterial overgrowth, the duodenum has been an untouchable intestinal segment for lengthening procedures owing to its close relationship with bilio-pancreatic structures and blood supply shared with the pancreas. Three children (age range, 0.5–7 years) with SBS and dilated duodenum underwent a novel surgical procedure of duodenal lengthening combined with a technical modification of serial transverse enteroplasty (STEP). Pre-STEP, jejunum length was 5, 35 and 45cm, respectively. Duodenal lengthening was performed with sequential transverse applications of an endoscopic stapler on the anterior and posterior wall of the duodenum to avoid bilio-pancreatic structure injury. Two patients underwent 3 duodenal firings (stapler of 35mm) and the third 5 firings (stapler of 45mm). Duodenal firings were 17%, 21% and 83% of the total firings. ResultsNo surgical complications occurred. One patient developed transient episodes of D-lactic acidosis. Two patients (5 and 45cm) were weaned off parenteral nutrition at 12months post-surgery and the remaining patient´s (35cm) parenteral calorie requirements have decreased by 60%. ConclusionDuodenal lengthening is effective since it tailors and increases the absorptive surface of the duodenum, even in cases of extreme SBS.

Pathophysiology of Short Bowel Syndrome

The human small intestine is organized with a proximal-to-distal gradient of mucosal structure and nutrient processing capacity. However, certain nutrients undergo site-specific digestion and absorption, such as iron and folate in the duodenum/jejunum vs vitamin B12 and bile salts in the ileum. Intestinal resection can result in short bowel syndrome (SBS) due to reduction of total and/or site-specific nutrient processing areas. Depending on the segment(s) of intestine resected, malabsorption can be nutrient specific (eg, vitamin B12 or fat) or sweeping, with deficiencies in energy, protein, and various micronutrients. Jejunal resections are generally better tolerated than ileal resections because of greater postresection adaptive capacity than that of the jejunum. Following intestinal resection, energy scavenging and fluid absorption become particularly important in the colon owing to loss of digestive and absorptive surface area in the resection portion. Resection-induced alterations in enteroendocrine cell abundance can further disrupt intestinal function. For example, patients with end jejunostomy have depressed circulating peptide YY and glucagon-like peptide 2 concentrations, which likely contribute to the rapid intestinal transit and blunted intestinal adaptation observed in this population. SBS-associated pathophysiology often extends beyond the gastrointestinal tract, with hepatobiliary disease, metabolic bone disease, D-lactic acidosis, and kidney stone formation being chronic complications. Clinical management of SBS must be individualized to account for the specific nutrient processing deficit within the remnant bowel and to mitigate potential complications, both inside and outside the gastrointestinal tract.

Gross and histopathology lesions of abomasum of kid died of Floppy kid syndrome

D-lactic acidosis or Floppy kid syndrome (FKS) is a disease condition in kids characterized by decline in blood pH and elevated anion gap resulting in metabolic acidosis. A case of six day old goat kid was reported at University Goat and Sheep farm with clinical signs and laboratory findings suggestive of FKS. In spite of intense therapy the kid succumbed to death on third day of treatment. Distended abomasum with hemorrhage was seen on gross observation. Histopathology revealed abomassitis with hemorrhagic streaks.

A Randomized Double Blind Controlled Safety Trial Evaluating d-Lactic Acid Production in Healthy Infants Fed a Lactobacillus reuteri-containing Formula.

BACKGROUNDd-Lactic acidosis in infants fed lactic acid bacteria-containing products is a concern.METHODSThe primary objective of this non-inferiority trial was to compare urinary d-lactic acid concentrations during the first 28 days of life in infants fed formula containing Lactobacillus reuteri (1.2 × 106 colony forming units (CFU)/ml) with those fed a control formula. The non-inferiority margin was set at a two-fold increase in d-lactic acid (0.7 mmol/mol creatinine, log-transformed). Healthy term infants in Greece were enrolled between birth and 72 hours of age, and block randomized to a probiotic (N = 44) or control (N = 44) group. They were exclusively fed their formulae until 28 days of age and followed up at 7, 14, 28, 112, and 168 ± 3 days. Anthropometric measurements were taken at each visit and tolerance recorded until 112 days. Urine was collected before study formula intake and at all visits up to 112 days and blood at 14 days.RESULTSd-Lactic acid concentration in the probiotic group was below the non-inferiority margin at 28 days: treatment effect −0.03 (95% confidence interval [CI]: [−0.48 to 0.41]) mmol/mol creatinine but was above the non-inferiority margin at 7 and 14 days—treatment effect 0.50 (95% CI: [0.05–0.96]) mmol/mol creatinine and 0.45 (95% CI: [0.00–0.90]) mmol/mol creatinine, respectively. Blood acid excess and pH, anthropometry, tolerance, and adverse events (AEs) were not significantly different between groups.CONCLUSIONIntake of L. reuteri-containing formula was safe and did not cause an increase in d-lactic acid beyond two weeks.

Formerly Obese, Now Thin and Confused: The Utility of Mnemonics in the Approach to Altered Mental Status

Altered mental status represents a common cause for admission to general medicine services. Often a significant workup ensues to define an underlying etiology. When a history of bariatric surgery with small bowel resection precedes the presentation, the differential diagnosis expands. We review a patient, having prior bariatric surgery and small bowel resection, who presents with altered mental status. After an extensive workup, she was diagnosed with a rare clinical problem, d-lactic acidosis. In presenting this case, we examine the use of mnemonics in medicine and how this can assist in solving clinical problems.

Successful correction of D-lactic acid neurotoxicity (drunken lamb syndrome) by bolus administration of oral sodium bicarbonate

Drunken lamb syndrome (DLS) has recently been described as lamb D-lactic acidosis syndrome (LDLAS). In 2012, 18 lambs aged between 7 days and 28 days with LDLAS were identified. Biochemically,...