Carbohydrate Malabsorption Research Articles

Is there dietary macronutrient malabsorption in children with environmental enteropathy?

Assessing the digestive and absorptive capacity of the gastro-intestinal tract (GIT) using minimally- or non-invasive methods, particularly in children, has been difficult owing to the complex physiology and variability in functional measurements. However, measuring GIT function is increasingly important with the emerging relevance of childhood environmental enteropathy (EE) as a mediating factor in linear growth faltering, severe acute malnutrition, poor oral vaccine uptake and impaired cognition. In EE, sub-optimal nutrient digestion and absorption (malabsorption) forms the critical link to the conditions mentioned above. The present narrative review discusses probable mechanisms that can cause malabsorption of macronutrients, along with mechanistic and experimental evidence, in children (if not, in adults) with EE. The strengths and limitations of the human experimental studies are examined in relation to a battery of existing and potential tests that are used to measure malabsorption. From the available studies conducted in children, lactose and fat malabsorption are more likely to occur in EE. Breath tests (non-invasive) measuring carbohydrate (13C-starch/sucrose/lactose), fat (13C-mixed triglyceride) and dipeptide (benzoyl-L-tyrosyl-L-1-13C-alanine) malabsorption with modifications to the existing protocols seem suitable for use in children with EE. Future research should focus on understanding the degree of macronutrient malabsorption using these tests, in different settings, and link them to functional outcomes (such as growth, muscle strength, cognition).

Contaminated well water driving d‐lactic acidosis in child with short bowel syndrome

Abstractd‐lactic acidosis is a rare type of lactic acidosis that typically presents in patients with short bowel syndrome (SBS). Clinical features include a high anion‐gap metabolic acidosis and acute onset of neurological impairment. The underlying pathology is thought to be due to altered gut flora and carbohydrate malabsorption in patients with altered gut anatomy. The treatment centers on correcting acid–base derangements, dietary modifications to decrease carbohydrate intake and antibiotics. We present a case of recurrent d‐lactic acidosis in a patient with SBS. In this unique case, we highlight the importance of considering the home environment when developing a treatment plan.

590. RESOLUTION OF SYMPTOMS AFTER OESOPHAGO-GASTRIC CANCER RESECTION (RESTORED)–STANDARDISING GASTROINTESTINAL SYMPTOMS AND CONDITIONS AFTER SURGERY: A MULTI-DISCIPLINARY EXPERT DELPHI STUDY

Abstract Background Oesophago-gastric cancer surgery negatively affects quality of life with a high post-operative symptom burden. Several conditions that may be diagnosed and treated after surgery are recognised. However, consensus regarding their definition and management is lacking. We aimed to develop consensus regarding the definition, investigation and management of the common symptoms and conditions, and triggers to consider disease recurrence, as a foundation for improving management and quality of life in these patients. Design Modified 2-round Delphi consensus study of a multidisciplinary expert panel. Results 86/127(67.7%) and 77/100(77.0%) responses were received in rounds 1 and 2. Consensus was achieved in defining 26 symptoms. For 10 conditions (anastomotic stricture, acid reflux, non-acid reflux, biliary gastritis, delayed gastric emptying, dumping syndrome, exocrine pancreatic insufficiency, bile acid diarrhoea, small intestinal bacterial overgrowth and carbohydrate malabsorption), definitions, diagnostic criteria, first and second-line investigation and first-line treatments were agreed. Consensus was not reached for third line investigation of some conditions, nor for second, third or fourth-line treatments for others. 12 of 14(85.7%) symptoms were agreed as triggers to consider cancer recurrence, during the early (< 1 year) and late (> 1 year) post-operative periods. Conclusion Expert consensus regarding symptoms, conditions and triggers to consider investigation for recurrence after oesophago-gastric cancer surgery was achieved. This will allow standardisation and timely diagnosis and treatment of post-operative conditions, reducing variation in care. It will facilitate comparative, prospective research to establish the incidence and response to treatment of these conditions, helping develop robust evidence to optimise patients’ quality of life.

Hydrogen breath test as a diagnostic tool

Introduction and Purpose: Hydrogen breath tests serve the crucial purpose of evaluating the absorption of nutrients in the small intestine, particularly when carbohydrates are not properly absorbed, leading to bacterial overgrowth. These tests are non-invasive, cost-effective, and widely accessible diagnostic tools used to assess various gastrointestinal disorders. The objective of this review is to evaluate the effectiveness and methodology of Hydrogen breath testing (HBT). State of knowledge: The disposal of hydrogen gas is essential for maintaining efficient microbial fermentation processes in the gut. Hydrogenotrophic microbes, including acetogens, methanogenic archaea, and sulfate-reducing bacteria, are responsible for this process. Hydrogen breath tests, conducted with substrates like glucose and lactulose, aid in diagnosing conditions such as small intestinal bacterial overgrowth (SIBO), lactose and fructose intolerance, and other carbohydrate absorption disorders. These tests generate a large volume of data, which can be analyzed using data mining techniques to uncover new hypotheses. Conclusions: Hydrogen breath tests, using various substrates, are effective in diagnosing gastrointestinal disorders such as SIBO and carbohydrate malabsorption. They offer valuable insights into microbial processes in the gut and can inform individualized treatment strategies. However, careful consideration of contraindications and proper test administration protocols is essential for accurate diagnosis and interpretation of results.

The role of carbohydrate malabsorption syndrome in the pathogenesis of rotavirus diarrhea (a literature review)

The aim – to summarize literature data on the pathogenetic mechanisms of the diarrheal syndrome development in children with rotavirus infection and to determine the role of carbohydrate malabsorption syndrome in it through a complex analysis of literature reviews and empirical studies. Rotavirus infection (RVI) remains the main cause of severe dehydrating gastroenteritis in children under five years of age. One of the most important pathogenetic links of rotavirus gastroenteritis is the development of osmotic diarrhea induced by carbohydrate malabsorption syndrome. Its development is associated with disaccharidase insufficiency and impaired absorption of monosaccharides in the small intestine. Carbohydrate malabsorption syndrome is found in 67.0–98.3 % of children with RVI. Its laboratory manifestations (an increase in levels of fecal carbohydrates and lactose) are observed starting from the first days of the disease, and the maximum indicators are recorded in the period from the fifth to the seventh day. Conclusions. Carbohydrate malabsorption syndrome is observed in the absolute majority of children with RVI, and its maximum severity is noted from the fifth to the seventh day of the disease, being realized mainly due to lactase deficiency. The severity of carbohydrate malabsorption syndrome can be influenced by concomitant pathological conditions, that lead to a decrease in the activity of disaccharidases in the small intestine, and the metabolic activity of the intestinal microbiota.

Algorithms or biomarkers in patients with lower DGBI?

Several organizations have proposed guidelines or clinical decision tools for the management of patients with disorders of gut-brain interactions (DGBI) affecting the lower digestive tract including irritable bowel syndrome and chronic idiopathic constipation. Such algorithms are based on sequential therapeutic trials and modifying the treatment strategy based on efficacy and adverse events. The aims of this review are to evaluate the evidence for efficacy of second- and third-line pharmacotherapies and to assess the evidence for the alternative option to manage subgroups of patients with symptoms suggestive of lower DGBI based on diagnostic tests or documented dysfunctions. The preeminent tests to identify such subgroups that present with symptoms that overlap with lower DGBI are detailed: digital rectal examination as well as anorectal manometry and balloon expulsion for evacuation disorders, detailed measurements of colonic transit, and diagnosis of bile acid diarrhea or carbohydrate malabsorption based on biochemical measurements. The review also addresses the cost implications of screening to exclude alternative diagnoses and the costs of therapy associated with the therapeutic options following an algorithmic approach to treatment from the perspective of society, insurer, or patient. Finally, the costs of the diagnostic tests to identify actionable biomarkers and the evidence of efficacy of individualized therapy based on formal diagnosis or documentation of abnormal functions are detailed in the review.

Total fermentable oligo-, di-, monosaccharides and polyols intake, carbohydrate malabsorption and gastrointestinal symptoms during a 56 km trail ultramarathon event.

To explore the relationship between nutritional intake, fermentable oligo-, di, monosaccharides and polyols, and carbohydrate malabsorption, with gastrointestinal symptoms during a 56 km trail ultramarathon event and identify differences in nutritional intake between runners with severe and non-severe gastrointestinal symptoms. Forty-four ultramarathoners recorded and self-reported dietary intake 3 days before, morning of, and during the ultramarathon with gastrointestinal symptoms obtained retrospectively and nutrient analysis via FoodWorks. Carbohydrate malabsorption was determined via breath hydrogen content pre- and post-race. Spearman's rank-order and Mann-Whitney U-tests were used to identify relationships and differences between groups. Total fermentable oligo-, di, monosaccharides and polyols intake were not associated with gastrointestinal symptoms, but weak associations were observed for lower energy (rs = -0.302, p = 0.044) and fat intake (rs = -0.340, p = 0.024) 3 days before with upper gastrointestinal symptoms and higher caffeine intake 3 days before with overall gastrointestinal symptoms (rs = 0.314, p = 0.038). Total fermentable oligo-, di-, monosaccharides and polyols intake and breath hydrogen were not different between those with severe versus non-severe symptoms (p > 0.05). Although those with severe symptoms had higher caffeine (p = 0.032), and total polyols intake (p = 0.031) 3 days before, and higher % energy from fat (p = 0.043) and sorbitol intake (p = 0.026) during the race, and slower ultramarathon finish times (p = 0.042). Total fermentable oligo-, di-, and monosaccharides intake and carbohydrate malabsorption were not associated with gastrointestinal symptoms. Additional research on the effect of fat, caffeine, and polyol intake on exercise-associated gastrointestinal symptoms is warranted and presents new nutritional areas for consideration when planning nutritional intake for ultramarathoners.

Congenital sucrase–isomaltase deficiency in Türkiye; a single center experience

Background Congenital sucrase–isomaltase deficiency (CSID) is a rare inherited carbohydrate malabsorption disorder caused by sucrase–isomaltase (SI) gene variants. In CSID, an autosomal recessively inherited disease, symptoms can also be seen in individuals with heterozygous mutations. Methods The variant spectrum was evaluated retrospectively in individuals who presented with chronic diarrhea between 2014 and 2022 and had undergone genetic testing of the SI gene considering CSID due to diet-related complaints. Results Ten patients with chronic diarrhea were genetically evaluated with SI gene sequencing. In patients diagnosed with CSID and whose symptoms improved with enzyme replacement therapy, the genetic mutation zygosity was found to be heterozygous at a rate of 90%. In 10% of the patients, the mutation was homozygous. Limiting consuming sucrose and isomaltose foods reduced the patients’ complaints, but the symptoms did not disappear completely. With the initiation of sacrosidase enzyme replacement therapy, the patient’s complaints completely disappeared. Conclusion In CSID, defined as an autosomal recessive disease, clinical symptoms can also be seen in heterozygous cases previously described as carriers, and these patients also benefit from sacrosidase enzyme replacement therapy. In light of these findings, the autosomal recessive definition of CSID does not fully characterize the disease. What is Known: CSID is a rare inherited carbohydrate malabsorption disorder caused by sucrase–isomaltase gene variants. In congenital sucrase–isomaltase deficiency, an autosomal recessively inherited disorder, symptoms can also be seen in individuals with heterozygous mutations. What is new: Severe disease symptoms can also be seen in heterozygous cases, which were thought to be carriers because the disease was previously described as autosomal recessive. Sacrosidase enzyme replacement therapy also eliminates the disease symptoms in patients with heterozygous CSID mutations. This is the second study on sucrase–isomaltase enzyme deficiency pediatric groups in Türkiye and Europe.

Nutrition and Disorders of Gut-Brain Interaction.

Disorders of gut-brain interaction (DGBIs) have a complex pathophysiology that is often characterized by a relationship between food ingestion and triggering of symptoms. Understanding of the underlying mechanisms and the role of nutrients as a therapeutic target are rapidly evolving. We performed a narrative review of the literature using the following keywords, their acronyms, and their associations: nutrients, disorders of gut-brain interaction; functional dyspepsia; malabsorption; irritable bowel syndrome; diarrhea; constipation. Functional dyspepsia displayed a significant correlation between volume, fat and/or wheat abundance, chemical composition of ingested food and symptoms of early satiety, fullness and weight loss. Carbohydrate malabsorption is related to enzyme deficiency throughout the GI tract. Food composition and richness in soluble vs. non-soluble fibers is related to constipation and diarrhea. The elimination of fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) has a significant and non-unidirectional impact on irritable bowel syndrome (IBS) symptoms. Food volume, nutritive and chemical composition, and its malabsorption are associated with symptom generation in DGBIs. Further multicenter, randomized-controlled clinical trials are needed to clarify the underlying pathophysiology.

Genetics of sucrose metabolism disorders in different population groups

The study of the genetic determinants of the disaccharidase activity opens up new prospects for improving diagnostics and choosing medical tactics in gastroenterology. The aim of the study was to systematize the data on the role of the sucrase-isomaltase gene (SI) in regulating sucrose metabolism and the contribution of SI mutations to the prevalence of sucrose malabsorption disorders (sucrase-isomaltase deficiency, SID) and certain forms of enterological pathology in different population groups. Material and methods. A review of the peer-reviewed scientific literature, mainly in the PubMed database (https://pubmed.ncbi.nlm.nih.gov) and eLibrary (https://elibrary.ru), was conducted using key words: carbohydrate malabsorption, sucrase, sucrase-isomaltase deficiency, sucrase-isomaltase SI gene. The search depth was not specified, but particular attention was paid to recent publications. The gnomAD database (https://www.ncbi.nlm. nih.gov/snp/rs781470490) was also used. Results. According to the review results, 37 out of 150 known SI gene mutations have been confirmed to contribute to reduced sucrase activity or restricted sucrase production. The prevalence of point mutations in the SI gene is estimated at 0.0006%, but carrier rates of the SI delAG deletion (rs781470490), manifested as homozygosity in SID, are very high (5-21%) in indigenous populations of Arctic regions in East Asia and America. Medicalgenetic research methods improve the accuracy of differential diagnosis of primary and secondary SID and other forms of disaccharide and polysaccharide malabsorption. The formation of databases on the prevalence of genetic determinants of sucrase-isomaltase insufficiency is a promising way to refine the epidemiology of SID. There is an increased (0.2-2.3%) risk of clinical manifestations of SID in homozygous carriers of the SI delAG mutation in the Chukotka, Kamchatka, and Northern Priochotye populations. Verification of reports on a less pronounced tendency to lipid metabolism disorders in SI delAG carriers compared with the control group is recommended. Conclusion. Manifestations of mutant SI variants in the phenotype are associated with the presence of accompanying carbohydrate malabsorption variants and specific gut microbiota. The SI 15Phe variant (rs9290264) may contribute to the development of irritable bowel syndrome.

Ulcerative Colitis with Henoch Schonlein Purpura in Pediatric Patient: A Case-Report

Background: Inflammatory bowel disease (IBD) is defined as idiopathic disorder which associated with inflammation of gastrointestinal tract. Ulcerative colitis (UC) and Chron's disease are the predominant forms of IBD. Henoch Schonlein Purpura and UC share some similar symptoms and can mimic each other especially in children. In this case report, we present an eight-year-old boy who had main complaint of recurrent bloody stools and abdominal pain. Diagnosis was made through history taking, physical examination, laboratory examination and colonoscopy in this patient. Case: A boy aged 8 years and 1 month had main complaint of bloody stools with fluid consistency. This complaint was accompanied by abdominal pain all over the abdominal region and vomiting. Upon physical examination, the child was in pain. The vital signs were within normal limits. Laboratory examination showed leukocytosis. The routine stool examination showed malabsorption of fat, protein, and carbohydrates, followed with positive erythrocytes, leukocytes, epithelium, bacteria, and yeast cells; but the stool culture was sterile. Gastroscopy and colonoscopy were performed which showed erosive gastritis, duodenitis, and proctitis. Discussion: The relationship between ulcerative colitis and HSP remains unknown. Recent research showed overproduction of IgA may induce chronic inflammation in the intestinal. While HSP is IgA/immune complex mediated, IBD is thought to be predominantly T-cell driven. Recently, in IBD patients especially those with ulcerative colitis, IgA were found in their histopathologic biopsy result. Conclusion: The relationship between ulcerative colitis and HSP remains unknown. Recent research has shown that the overproduction of IgA may induce chronic inflammation in the intestinal. As such, symptoms of both diseases may mimic each other as seen in our patients.

OGC P28 Gastrointestinal symptoms and disorders after oesophago-gastric cancer surgery: The RESTORE modified Delphi survey

Abstract Background Oesophago-gastric (OG) cancer surgery is life-changing with a significant impact on quality of life (QOL). OG cancer surgery reconfigures the upper gastrointestinal (GI) tract altering its physiological function. Certain disorders such as anastomotic stricture are well recognised whereas others, such as small intestinal bacterial overgrowth, are increasingly being diagnosed. As multimodality treatment improves survival, more poly-symptomatic patients are living with these disorders as a consequence of surgery. We aimed to establish consensus on the definitions of relevant symptoms and disorders, as well as appropriate investigation and treatment. Standardisation will form a foundation for optimising QOL in this growing patient group. Methods This on-line modified Delphi study focused on patients after oesophagectomy, gastrectomy or subtotal gastrectomy for cancer (OG cancer surgery). The survey covered symptoms, common conditions, and symptoms triggering investigation for recurrence. The survey was designed using non-systematic reviews and expert opinion. Items were rated from 1 (completely disagree) to 9 (absolutely agree). Multi-disciplinary experts were identified through word of mouth and expressions of interest at previous conferences. Two rounds were completed, with some revisions after first round review. Median ratings were determined. Consensus agreement was judged as 70% or more respondents in agreement (7-9) and less than 15% disagreement (1-3). Results 86 and 77 complete surveys were received in rounds 1 and 2. Respondents were multidisciplinary, including OG surgeons, oncologists, gastroenterologists, radiologists, dietitians and nurse specialists. 7 upper GI, 13 non-specific and 6 lower GI symptom definitions were agreed. Clinical definitions, diagnostic criteria, first line investigations and treatments were agreed for 10 conditions: anastomotic stricture, acid reflux, non-acid reflux oesophagitis, biliary gastritis, delayed gastric emptying, dumping syndrome, exocrine pancreatic insufficiency, bile acid diarrhoea, small intestinal bacterial overgrowth and carbohydrate malabsorption. Agreement was also reached across many second-line investigations and treatments, and 12 of 14 (86%) symptom triggers to investigate for recurrence. Conclusions The RESTORE multidisciplinary consensus study has established a foundation for assessing and treating 10 conditions negatively affecting QOL after OG cancer surgery. Standardised symptom definitions will guide diagnostic assessments. Agreed condition definitions and diagnostic criteria will allow robust measurement of their incidence, and evaluation of treatment effects. Future work will aim to develop algorithms for managing these conditions. This work will raise standards of diagnosis and treatment of conditions that affect patients after OG cancer surgery, allowing collection of robust data to evaluate improvements in symptoms and QOL.

Interaction between the α-glucosidases, sucrase-isomaltase and maltase-glucoamylase, in human intestinal brush border membranes and its potential impact on disaccharide digestion.

The two major intestinal α-glycosidases, sucrase-isomaltase (SI) and maltase-glucoamylase (MGAM), are active towards α-1,4 glycosidic linkages that prevail in starch. These enzymes share striking structural similarities and follow similar biosynthetic pathways. It has been hypothesized that starch digestion can be modulated via "toggling" of activities of these mucosal α-glycosidases, suggesting a possible interaction between these two enzyme complexes in the intestinal brush border membrane (BBM). Here, the potential interaction between SI and MGAM was investigated in solubilized BBMs utilizing reciprocal pull down assays, i.e., immunoprecipitation with anti-SI antibody followed by Western blotting with anti-MGAM antibody and vice versa. Our results demonstrate that SI interacts avidly with MGAM concomitant with a hetero-complex assembly in the BBMs. This interaction is resistant to detergents, such as Triton X-100 or Triton X-100 in combination with sodium deoxycholate. By contrast, inclusion of sodium deoxycholate into the solubilization buffer reduces the enzymatic activities towards sucrose and maltose substantially, most likely due to alterations in the quaternary structure of either enzyme. In view of their interaction, SI and MGAM regulate the final steps in starch digestion in the intestine, whereby SI assumes the major role by virtue of its predominant expression in the intestinal BBMs, while MGAM acts in auxiliary supportive fashion. These findings will help understand the pathophysiology of carbohydrate malabsorption in functional gastrointestinal disorders, particularly in irritable bowel syndrome, in which gene variants of SI are implicated.

Sucraid (sacrosidase) is the only treatment for CSID: should there be a better option?

Sucraid (sacrosidase) is the only treatment for CSID: should there be a better option?

Comparison of Therapeutic Feed (Different recipes) during Stabilization Phase for the management of Children with Severe Acute Malnutrition (SAM)

Objective: To compare the feeding of sugar based F75, Cooked rice based F75 and Enhanced cooked rice based modified F75 during stabilization phase for the management of children with SAM (Severe Acute Malnutrition) aged 6-60 months presented with diarrhea. Study Design: An open-label randomized controlled trial. Place and Duration: Stabilization center, Children’s Hospital and Institute of Child Health Multan from 1st January 2018 to 30th November 2019. Methodology: The total 270 children, (who were under 5 years of age and admitted to the stabilization center for complicated Severe Acute Malnutrition (SAM) during study duration) were divided into three groups of 90 patients each. Group A was given Standard sugar-based F75, Group B was given Cooked Rice based F75 and Group C was given Enhanced cooked rice based modified F75. Clinical and biochemical parameters of patients were analyzed at day 1, day 3 and day 7 after admission. Results: The age of our patients was 16.7 ± 12.2 months with male to female ratio of 1.2:1. The mid upper arm circumference (MUAC) of cases was 10.07±0.86 cm. More than half of the children had diarrhea at admission. During the initial stabilization phase (day 1 to day 7), number of patients with complains of diarrhea increased from 57.78% to 65.54% in group A while it reduced from 52.22% to 15.54% in group B and from 62.16% to 7.77% in group C. Conclusion: Modified rice base therapeutic feeding is more effective for treatment of SAM with diarrhea as compared to standard sugar based F75 formula. Keywords: Children, Diarrhoea, Severe Acute Malnutrition, Stabilization Phase, Carbohydrate Malabsorption, Diarrhea, F75 Rice Based Therapeutic Feed How to Cite This: Khan S, Iqbal I, Ali I, Batool N, Abbas A, Arshad R. Comparison of Therapeutic feed (different recipes) during Stabilization Phase for the management of Children with Severe Acute Malnutrition (SAM). Isra Med J. 2022; 14(3): 108-112. DOI: https://doi.org/10.55282/imj.oa1140

Long-term Gastrointestinal Sequelae Following COVID-19: A Prospective Follow-up Cohort Study

Background and AimsCOVID-19 is associated with long-term gastrointestinal sequelae; however, prospective longitudinal data are sparse. We prospectively studied the frequency, spectrum and risk factors of post infection functional gastro-intestinal disorders/disorders of gut-brain interaction (PI-FGID/DGBI) following COVID-19.Methods320 cases with COVID-19 and two control groups: (Group-A) 320 healthy spouses/family controls and (Group B) 280 healthy COVID serology-negative controls were prospectively followed up at 1,3 and 6 months using validated Rome IV criteria to evaluate the frequency of PI-FGID/DGBI.ResultsOf 320 cases, at 1 month, 36 (11.3%) developed FGID symptoms. Persistent symptoms were noted in 27 (8.4%) at 3 months, and in 21 (6.6%) at 6 months. At 3 months, 8 (2.5%) had irritable bowel syndrome, 7 (2.2%) had functional diarrhea, 6 (1.9%) had functional dyspepsia, 3 (0.9%) had functional constipation, 2 (0.6%) had FD-IBS overlap, and 1 (0.3%) had functional abdominal bloating/distension. Among symptomatic individuals at 3 months, 8 (29.6%) were positive for isolated carbohydrate malabsorption, 1 (3.7%) was positive for post infection malabsorption syndrome (PI-MAS) and 1 (3.7%) was positive for Intestinal methanogen overgrowth (IMO). None of the healthy controls developed FGID up to 6 months of follow up (p<0.01). Predictive factors at 3 and 6 months were severity of infection (p<0.01) and presence of GI symptoms at the time of infection (p<0.01).ConclusionCOVID-19 led to significantly higher number of new onset PI-FGID/DGBI compared to healthy controls at 3 and 6 months of follow-up. If further investigated some patients can be diagnosed with underlying malabsorption.

Supervised Machine Learning for Predicting Carbohydrate Malabsorptions Using Hydrogen Breath Tests

Abstract Introduction: Carbohydrate malabsorptions symptoms include intestinal fluid retention, causing diarrhea and abdominal distention. The aim of this work is to create a machine learning model that predicts carbohydrate malabsorption using H2 measurements from lactose and fructose tolerance tests. Methods: We compare the predictive ability of popular classifiers with classifiers that are specifically designed for time series data. Our approach was implemented using sklearn and sktime Python machine learning libraries. Results: The highest predictive ability for the fructose dataset was achieved using a Random Forest Classifier (balanced accuracy = 0.91). In contrast, the highest predictive ability (balanced accuracy = 0.81) for the lactose dataset was obtained using an IndividualTDE time classifier. Conclusion: Our results indicate a high predictive ability for distinguishing between carbohydrate malabsorptions. However, the detection of SIBO is challenging but adapted time classifier models could reach higher performances compared to standard methods. Our results could establish the basis of an expert system for diagnosing carbohydrate malabsorptions and SIBO, respectively.

Sucrose intolerance in adults with common functional gastrointestinal symptoms

Sucrose intolerance is a form of carbohydrate malabsorption caused by sucrase-isomaltase deficiency that is more common than recognized. Its symptoms include postprandial cramping, bloating, gas, and diarrhea, which are difficult to distinguish from irritable bowel syndrome. The gold standard test for diagnosing sucrase deficiency is a sucrase enzyme assay of duodenal biopsies obtained by endoscopy. Hydrogen-methane or 13C-sucrose breath tests are noninvasive methods to screen for sucrose malabsorption. This chart review included 258 consecutive adults (47 men and 211 women) with chronic unexplained gastrointestinal symptoms and suspected sucrose intolerance who were screened with a hydrogen-methane or 13C-sucrose breath test. The incidence of sucrose malabsorption with two different hydrogen-methane breath tests was 34.4% (21/61) (Commonwealth Diagnostics International, Inc., Salem, MA) and 40% (20/50) (Aerodiagnostics, Concord, MA). The incidence of sucrose malabsorption with the 13C-sucrose breath test was 26.5% (39/147). In a subgroup of patients with positive breath tests and clinical follow-up, counseling regarding diet and/or enzyme replacement led to symptomatic improvement in 26/43 (60%). In conclusion, sucrose malabsorption may present with irritable bowel syndrome symptoms in a proportion of adult patients, and breath tests may be useful in identifying sucrose malabsorption and differentiating it from other gastrointestinal disorders.

Loss of Serum Glucocorticoid-Inducible Kinase 1 SGK1 Worsens Malabsorption and Diarrhea in Microvillus Inclusion Disease (MVID)

Microvillus inclusion disease (MVID), a lethal congenital diarrheal disease, results from loss of function mutations in the apical actin motor myosin VB (MYO5B). How loss of MYO5B leads to both malabsorption and fluid secretion is not well understood. Serum glucocorticoid-inducible kinase 1 (SGK1) regulates intestinal carbohydrate and ion transporters including cystic fibrosis transmembrane conductance regulator (CFTR). We hypothesized that loss of SGK1 could reduce CFTR fluid secretion and MVID diarrhea. Using CRISPR-Cas9 approaches, we generated R26CreER;MYO5Bf/f conditional single knockout (cMYO5BKO) and R26CreER;MYO5Bf/f;SGK1f/f double knockout (cSGK1/MYO5B-DKO) mice. Tamoxifen-treated cMYO5BKO mice resulted in characteristic features of human MVID including severe diarrhea, microvillus inclusions (MIs) in enterocytes, defective apical traffic, and depolarization of transporters. However, apical CFTR distribution was preserved in crypts and depolarized in villus enterocytes, and CFTR high expresser (CHE) cells were observed. cMYO5BKO mice displayed increased phosphorylation of SGK1, PDK1, and the PDK1 target PKCι in the intestine. Surprisingly, tamoxifen-treated cSGK1/MYO5B-DKO mice displayed more severe diarrhea than cMYO5BKO, with preservation of apical CFTR and CHE cells, greater fecal glucose and reduced SGLT1 and GLUT2 in the intestine. We conclude that loss of SGK1 worsens carbohydrate malabsorption and diarrhea in MVID.

Congenital Rare Diseases Causing Persistent Diarrhea in the Newborn: A Single Center Experience.

Congenital diarrheal disorders (CDDs) are a heterogeneous group of inherited diseases that typically occur in the first weeks of life or can present later in life after the introduction of different nutrients; they can cause life-threatening severe dehydration and electrolyte disturbances. This study was conducted to characterize the causes of monogenic CDDs, and their clinical consequences. Clinical characteristics of 31 patients with CDDs that occurred in the first month of life and lasted more than 2 weeks were analyzed retrospectively. The patients were divided into groups according to the current CDD classification. The rate of consanguinity among parents was 77.4%. Of the patients, 16 (51.6%) were female and 15 (48.4%) were male. The underlying genetic defect was determined in 26 (83.9%) patients. The most common etiologic factors were digestive disorders of food and absorption and transport of electrolytes (58.1%, 18/31) (most of them being carbohydrate malabsorption disorders, 12/18) and intestinal immune system disorders (9.6%, 3/31). Total parenteral nutrition (TPN) was given to 45.2% (14/31) of the patients. Mortality rate was 28.5% (8/28). In conclusion, early diagnosis and treatment of CDDs with high morbidity and mortality is extremely important in terms of prognosis. Clinical and laboratory findings, stool characteristics, histopathological findings and the effects of dietary therapy are the primary and most important steps that lead to accurate diagnosis. In addition, advanced diagnostic possibilities, including genetic analyses, are essential for diagnosing underlying diseases.