Intestinal Disaccharidase Deficiency in Adults: Evaluation and Treatment.

PURPOSE OF REVIEW: Disaccharidase deficiency in adults causes carbohydrate malabsorption, resulting in symptoms which significantly overlap with irritable bowel syndrome (IBS). This article discusses the diagnosis and treatment of disaccharidase deficiency within the context of recent literature. RECENT FINDINGS: Disaccharidase deficiency in adults is more common than previously thought, which includes lactase, sucrase, maltase and isomaltase enzymes. Deficiency in disaccharidases, which are produced by the intestinal brush border, will interfere with the breakdown and absorption of carbohydrates and may result in abdominal pain, gas, bloating and diarrhea. Patients deficient in all 4 disaccharidases are known as having "pan-disaccharidase" deficiency, which has a distinct phenotype with more reported weight loss than patients deficient in one enzyme. IBS patients who do not respond to low FODMAP dietary restriction may have undiagnosed disaccharidase deficiency and may benefit from testing. Diagnostic testing methods are limited to duodenal biopsies, which is the gold standard, and breath testing. Dietary restriction and enzyme replacement therapy have been shown to be effective treatments in these patients. Disaccharidase deficiency is an underdiagnosed condition in adults with chronic GI symptoms. Patients who do not respond to traditional treatment strategies for DBGI may benefit from testing for disaccharidase deficiency. Further studies delineating the distinctions between disaccharidase deficient patients and those with other motility disorders are needed.

Biomarkers for Bile Acid Malabsorption in Diarrhea-predominant Irritable Bowel Syndrome: A Systematic Review and Meta-analysis.

BACKGROUND AND AIM: A clear relationship of biological indexes between bile acid malabsorption (BAM) and diarrhea-predominant irritable bowel syndrome (IBS-D) has not been well analyzed. This meta-analysis aimed to establish a more convenient method to diagnose BAM in IBS-D patients by comparing the differences in biomarkers between IBS-D patients and healthy people. METHODS: Multiple databases were searched for relevant case-control studies. Indicators used to diagnose BAM included 75 Se-homocholic acid taurine (SeHCAT), 7α-hydroxy-4-cholesten-3-one(C4), fibroblast growth factor-19 and 48-hour fecal bile acid (48FBA). The rate of BAM (SeHCAT) was calculated by using a random-effect model. The levels of C4, FGF19, and 48FBA were compared, and the overall effect size was combined by a fixed effect model. RESULTS: The search strategy identified 10 relevant studies comprising 1034 IBS-D patients and 232 healthy volunteers. The pooled rate of BAM in IBS-D patients was 32% (according to SeHCAT; 95% CI: 24%-40%). The level of C4 in IBS-D patients was significantly higher than that in the control group (2.86 ng/mL; 95% CI: 1.09, 4.63); The level of FGF19 was significantly lower than that in the control group (-33.97 pg/mL; 95% CI: -51.13, -16.82); The level of 48FBA was significantly higher than that in the control group (0.059; 95% CI: 0.41, 0.77). CONCLUSIONS: The results mainly concluded serum C4 and FGF19 levels in IBS-D patients. Most of the studies have different normal cutoff points of serum C4 and FGF19 levels; the performance of each test should be further estimated. By comparing the levels of these biomarkers, BAM in patients with IBS-D could be identified more accurately, which would lead to more effective treatment.

Gastrointestinal Conditions: Malabsorption Syndromes.

Malabsorption syndromes are a heterogenous group of conditions that can cause distressing gastrointestinal symptoms. Celiac disease is most common and is triggered by exposure to gluten. Tissue transglutaminase immunoglobulin A is the diagnostic test of choice; management is gluten avoidance. Lactose intolerance is caused by absence or declining levels of the enzyme lactase. Diagnosis typically is clinical, but breath tests can be helpful if diagnosis is uncertain. Management is lactose avoidance. Bile acid malabsorption results in unabsorbed bile acids in the colon, leading to diarrhea. The 75selenium homotaurocholic acid test is most accurate but is not widely available. Therefore, a trial of bile acid sequestrants (typically cholestyramine) is a reasonable alternative when the diagnosis is suspected. Exocrine pancreatic insufficiency is caused by decreased production of pancreatic enzymes, typically occurring in patients with preexisting pancreatic damage from alcohol, surgery, radiation, diabetes, or cystic fibrosis. Diagnosis involves fecal fat or fecal elastase-1 tests. Management is pancreatic enzyme replacement. Small intestinal bacterial overgrowth is caused by pathologic overgrowth of the small bowel microbiome. Diagnosis is by jejunal biopsy or, more commonly, breath tests. Antibiotics (typically rifaximin) are the initial management. Other options include dietary changes, probiotics, and prokinetic drugs.

Incidence, Diagnosis and Management of Malabsorption Following Oesophagectomy: a Systematic Review.

BACKGROUND: Survival following oesophagectomy for cancer is improving, resulting in increased focus on quality of life and survivorship. Malabsorption syndrome is multifactorial and includes exocrine pancreatic insufficiency (EPI), small intestinal bacterial overgrowth (SIBO) and bile acid malabsorption (BAM). The aim of this study was to evaluate the reported incidence and management of malabsorption syndromes post-oesophagectomy. METHODS: A systematic search of PubMed, EMBASE, MEDLINE, Scopus and the Cochrane Library evaluating incidence, diagnosis and management of malabsorption was performed for studies published until December 2021. RESULTS: Of 464 identified studies, eight studies (n = 7 non-randomised longitudinal studies) were included where patients were identified with malnutrition following oesophagectomy. Studies included a combined sample of 328 (range 7-63) patients. Malabsorption syndromes including EPI, SIBO and BAM occurred in 15.9-100%, 37.8-100% and 3.33-100% over 21 days-60 months, 1-24 months and 1-24 months respectively. There was no consensus definition for EPI, SIBO or BAM, and there was variation in diagnostic methods. Diagnostic criteria varied from clinical (gastrointestinal symptoms or weight loss), or biochemical (faecal elastase, hydrogen breath test and Selenium-75-labelled synthetic bile acid measurements). Treatment modalities using pancreatic enzyme replacement, rifaximin or colesevelam showed improvement in symptoms and weight in all studies, where investigated. CONCLUSIONS: Malabsorption syndromes following oesophagectomy are under-recognised, and thus under-reported. The resultant gastrointestinal symptoms may have a negative effect on post-operative quality of life. Current literature suggests benefit with outlined therapies; however, greater understanding of these conditions, their diagnosis and management is required to further understand which patients will benefit from treatment.

Malabsorption Spectrums in India.

Among the causes of malabsorption, tropical sprue is one of the leading cause.Several reports indicating that celiac disease, now being recognised more frequently. MATERIAL: 94 patients, aged more than 12 years, presenting with Chronic diarrhoea and malabsorption syndrome were analyzed by clinical presentation, endoscopic and histopathological examination.The spectrum of disease in these patients and features differentiating celiac disease and tropical sprue are reported here. OBSERVATION: Most common cause was Celiac Disease (65%), followed by Tropical Sprue (21%), common variable immunodeficiency (2%), lymphangiectasia (1%), idiopathic (3%). Patients with celiac disease were younger,having anemia, scalloping of folds,moderate or severe villous atrophy, crypt hyperplasia, diffuse epithelial damage. Patients with tropical sprue were older and more often normal duodenal epithelium. CONCLUSION: Malabsorption, a disease which is often missed and not recognised by clinicians. A meticulous search for diagnosis is required.

Two cases of microvillus inclusion disease caused by MYO5B deficiency with prenatal abnormalities.

BACKGROUNDS: Microvillus inclusion disease (MVID) characterizes as intractable life-threatening watery diarrhea malnutrition after birth. MATERIALS & METHODS: Here we describe two patients with prenatal ultrasound findings of bowel dilation or increased amniotic fluid volume presented intractable diarrhea after birth. Exome sequencing and Intestinal biopsy were performed for the patients and their parents to reveal the underlying causes. The mutations were verified by Sanger sequencing and quantitative polymerase chain reaction. RESULTS: Exome sequencing revealed that both of the patients carrying MYO5B compound heterozygote mutations that were inherited from their parents. CONCLUSION: Here we describe two cases with MVID caused by MYO5B deficiency, which was the most common caused with prenatal ultrasound findings of bowel dilation and increased amniotic fluid volume. Due to the lack of effective curative therapies, early diagnosis even in prenatal of MVID can provide parents with better genetic counseling on the fetal prognosis.

Fructose malabsorption: causes, diagnosis and treatment.

This review intends to act as an overview of fructose malabsorption (FM) and its role in the aetiology of diseases including, but not limited to, irritable bowel syndrome (IBS) and infantile colic and the relationship between fructose absorption and the propagation of some cancers. IBS results in a variety of symptoms including stomach pains, cramps and bloating. Patients can be categorised into two groups, depending on whether the patients' experiences either constipation (IBS-C) or diarrhoea (IBS-D). FM has been proposed as a potential cause of IBS-D and other diseases, such as infantile colic. However, our knowledge of FM is limited by our understanding of the biochemistry related to the absorption of fructose in the small intestine and FM's relationship with small intestinal bacterial overgrowth. It is important to consider the dietary effects on FM and most importantly, the quantity of excess free fructose consumed. The diagnosis of FM is difficult and often requires indirect means that may result in false positives. Current treatments of FM include dietary intervention, such as low fermentable oligo-, di-, monosaccharides and polyols diets and enzymatic treatments, such as the use of xylose isomerase. More research is needed to accurately diagnose and effectively treat FM. This review is designed with the goal of providing a detailed outline of the issues regarding the causes, diagnosis and treatment of FM.

Ophthalmologic evaluation in vitamin-E deficiency: A case report.

A 41-year-old woman has come to our attention complaining of decreased visual acuity and monocular diplopia associated with upper and lower limb hypoesthesia. Malabsorption syndrome with vitamin A and E deficiency developed after a bariatric biliopancreatic diversion. The clinical ophthalmological signs and symptoms improved after oral vitamin supplementation therapy. The past medical history is essential in the case of a patient complaining of visual symptoms compatible with vitamin deficiency in order to detect the cause and to start a prompt therapy to avoid irreversible neurological and visual sequelae. The clinical features of our case closely resemble other cases described in the literature of patients affected by vitamin A and E deficiency secondary to malabsorption syndrome.

Bile Acid Malabsorption in Patients with Neuroendocrine Tumors.

BACKGROUND: Chronic diarrhea in patients with neuroendocrine tumors (NET) may be caused by bioactive products of NET, bile acid malabsorption (BAM), ileal resection (IR) or steatorrhea. AIM: To quantitate BA and fat malabsorption in NET with diarrhea. METHODS: Part of evaluation in medical oncology clinical practice, 67 patients [42F, 25 M; median age 64.0 y (17.0 IQR)] with well-differentiated NET and diarrhea underwent clinically indicated measurements of 48-h fecal BA [(FBA), fecal weight (normal < 400 g/48 h), fecal fat (normal < 7 g/day) in n = 52] and fasting serum 7αC4 (marker of hepatic BA synthesis, n = 30) between 01/2018 and 11/2020. IR had been performed in 45 patients. BAM diagnosis was based on FBA criteria: elevated total FBA (> 2337 µmol/48 h) or > 10% primary FBA or combination > 4% primary FBA plus > 1000 µmol total FBA/48 h. We also measured fecal elastase (for pancreatic insufficiency) in 13 patients. RESULTS: BAM was present in 48/52 (92%) patients with NET. There were significant correlations between total FBA and 48-h fecal weight (Rs = 0.645, P < 0.001). Mean length of IR was 47 cm; in patients with IR < 25 cm, total FBA was elevated in 85% and primary FBA > 10% in 69%. In 22 patients with no IR, 13/15 tested (87%) had BAM. Among 6 patients with pancreatic NET and no IR, 80% had BAM. Fecal fat was ≥ 15 g/day in 18/42 (43%). In 4/17 (24%) with IR < 25 cm and 8/19 (42%) patients with IR > 25 cm fecal fat was 44.0 (40.5) and 38.0 (38.0)g/day, respectively. CONCLUSION: A majority of patients with NET and diarrhea had BAM, even with < 25 cm or no IR.

Aberrant Epithelial Differentiation Contributes to Pathogenesis in a Murine Model of Congenital Tufting Enteropathy.

BACKGROUND & AIMS: Congenital tufting enteropathy (CTE) is an intractable diarrheal disease of infancy caused by mutations of epithelial cell adhesion molecule (EpCAM). The cellular and molecular basis of CTE pathology has been elusive. We hypothesized that the loss of EpCAM in CTE results in altered lineage differentiation and defects in absorptive enterocytes thereby contributing to CTE pathogenesis. METHODS: Intestine and colon from mice expressing a CTE-associated mutant form of EpCAM (mutant mice) were evaluated for specific markers by quantitative real-time polymerase chain reaction, Western blotting, and immunostaining. Body weight, blood glucose, and intestinal enzyme activity were also investigated. Enteroids derived from mutant mice were used to assess whether the decreased census of major secretory cells could be rescued. RESULTS: Mutant mice exhibited alterations in brush-border ultrastructure, function, disaccharidase activity, and glucose absorption, potentially contributing to nutrient malabsorption and impaired weight gain. Altered cell differentiation in mutant mice led to decreased enteroendocrine cells and increased numbers of nonsecretory cells, though the hypertrophied absorptive enterocytes lacked key features, causing brush border malfunction. Further, treatment with the Notch signaling inhibitor, DAPT, increased the numbers of major secretory cell types in mutant enteroids (graphical abstract 1). CONCLUSIONS: Alterations in intestinal epithelial cell differentiation in mutant mice favor an increase in absorptive cells at the expense of major secretory cells. Although the proportion of absorptive enterocytes is increased, they lack key functional properties. We conclude that these effects underlie pathogenic features of CTE such as malabsorption and diarrhea, and ultimately the failure to thrive seen in patients.

Effect of Gluten Ingestion and FODMAP Restriction on Intestinal Epithelial Integrity in Patients with Irritable Bowel Syndrome and Self-Reported Non-Coeliac Gluten Sensitivity.

SCOPE: Since epithelial barrier dysfunction has been associated with gluten and fermentable oligosaccharide, disaccharide, monosaccharide, and polyols (FODMAPs), the effect of alterations in FODMAP a gluten intake on epithelial barrier function in patients with irritable bowel syndrome (IBS) who self-reported gluten sensitivity. METHODS AND RESULTS: Circulating concentrations of markers of epithelial injury (syndecan-1 and intestinal fatty acid-binding protein) and bacterial translocation (lipopolysaccharide-binding protein and soluble CD14) are measured while consuming habitual gluten-free diet and during blinded challenges with gluten or placebo on a background of low FODMAP intake. In 33 patients, only syndecan-1 concentrations during their habitual diet are elevated (median 43 ng mL-1 ) compared with 23 ng mL-1 in 49 healthy subjects (p < 0.001). On a low FODMAP diet, symptoms are reduced and levels of syndecan-1 (but not other markers) fell by a median 3335% (p < 0.001) irrespective of whether gluten is present or not. CONCLUSION: Gluten ingestion has no specific effect on epithelial integrity or symptoms in this cohort, but reducing FODMAP intake concomitantly reduces symptoms and reverses apparent colonic epithelial injury. These findings highlight the heterogeneity of populations self-reporting gluten sensitivity and implicate FODMAPs in colonic injury in IBS.

Choice of Lipid Emulsion Determines Inflammation of the Gut-Liver Axis, Incretin Profile, and Insulin Signaling in a Murine Model of Total Parenteral Nutrition.

SCOPE: The aim of this study is to test whether the choice of the lipid emulsion in total parenteral nutrition (TPN), that is, n-3 fatty acid-based Omegaven versus n-6 fatty acid-based Intralipid, determines inflammation in the liver, the incretin profile, and insulin resistance. METHODS AND RESULTS: Jugular vein catheters (JVC) are placed in C57BL/6 mice and used for TPN for 7 days. Mice are randomized into a saline group (saline infusion with oral chow), an Intralipid group (IL-TPN, no chow), an Omegaven group (OV-TPN, no chow), or a chow only group (without JVC). Both TPN elicite higher abundance of lipopolysaccharide binding protein in the liver, but only IL-TPN increases interleukin-6 and interferon-γ, while OV-TPN reduces interleukin-4, monocyte chemoattractant protein-1, and interleukin-1α. Insulin plasma concentrations are higher in both TPN, while glucagon and glucagon-like peptide-1 (GLP-1) were higher in IL-TPN. Gluconeogenesis is increased in IL-TPN and the nuclear profile of key metabolic transcription factors shows a liver-protective phenotype in OV-TPN. OV-TPN increases insulin sensitivity in the liver and skeletal muscle. CONCLUSION: OV-TPN as opposed to IL-TPN mitigates inflammation in the liver and reduces the negative metabolic effects of hyperinsulinemia and hyperglucagonemia by "re-sensitizing" the liver and skeletal muscle to insulin.

Common Diarrheal Illnesses in the Elderly.

Diarrhea is a fairly common problem among the elderly that has a higher morbidity and mortality compared with the general population. There are multiple reasons for diarrhea in the elderly that can be stratified by different mechanisms: infectious, osmotic, secretory, inflammatory, and malabsorptive. Oral hydration and dietary management are the basic management principles for all forms of diarrhea but specific treatment should address the root cause of diarrhea in order to improve outcomes.

Fructose Malabsorption in Chilean Children Undergoing Fructose Breath Test at a Tertiary Hospital.

ABSTRACT: Fructose is a highly abundant carbohydrate in western diet and may induce bowel symptoms in children as in adults. The main objective of this study is to describe the frequency of fructose malabsorption (FM) in symptomatic patients 18 years or younger undergoing fructose breath test in a single tertiary center between 2013 and 2018, and to evaluate whether certain symptoms are related to positivity of the test. Out of 273 tests 183 (67%) were compatible with FM. The most frequent pretest symptom in the overall study population was bloating (83%), followed by abdominal pain (73%). Patients with positive test were younger than those with a negative test (median 5 vs 8 years, P < 0.001). In multivariate analysis, which included age, sex, and symptoms (diarrhea, abdominal pain, bloating, nausea), only age <6 years (odds ratio 2.93, 95% confidence interval 1.64-5.23) and absence of nausea (odds ratio = 3.32, 95% confidence interval 1.56-7.05) were associated with FM.

Is Gluten the Only Culprit for Non-Celiac Gluten/Wheat Sensitivity?

The gluten-free diet (GFD) has gained increasing popularity in recent years, supported by marketing campaigns, media messages and social networks. Nevertheless, real knowledge of gluten and GF-related implications for health is still poor among the general population. The GFD has also been suggested for non-celiac gluten/wheat sensitivity (NCG/WS), a clinical entity characterized by intestinal and extraintestinal symptoms induced by gluten ingestion in the absence of celiac disease (CD) or wheat allergy (WA). NCG/WS should be regarded as an "umbrella term" including a variety of different conditions where gluten is likely not the only factor responsible for triggering symptoms. Other compounds aside from gluten may be involved in the pathogenesis of NCG/WS. These include fructans, which are part of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), amylase trypsin inhibitors (ATIs), wheat germ agglutinin (WGA) and glyphosate. The GFD might be an appropriate dietary approach for patients with self-reported gluten/wheat-dependent symptoms. A low-FODMAP diet (LFD) should be the first dietary option for patients referring symptoms more related to FODMAPs than gluten/wheat and the second-line treatment for those with self-reported gluten/wheat-related symptoms not responding to the GFD. A personalized approach, regular follow-up and the help of a skilled dietician are mandatory.

[Moderate anaemia refractory to oral iron in a pregnant woman with a history of bariatric surgery]. / Anemia moderada refractaria al hierro oral en una gestante con antecedente de cirugía bariátrica.

INTRODUCTION: Introduction: bariatric surgery involves nutritional and trace element deficiencies that may have a negative impact if not treated properly, especially in situations such as pregnancy. Case report: a patient who underwent biliopancreatic diversion surgery without subsequent therapeutic adherence consults due to edema; findings included 29-week gestation (type 1 intrauterine growth restriction) and moderate anemia. Vitamin supplementation, oligoelements, enteral nutrition, and intravenous iron were restarted. Due to poor hemoglobin response with repleted iron deposits, recombinant human erythropoietin was associated. Discussion: the most frequent nutritional deficiencies after malabsorptive bariatric surgery are sideropenia and hypoproteinemia. Sideropenia and anemia increase the risk of preterm delivery, low weight, and perinatal mortality. In patients with inadequate response to intravenous iron, treatment with recombinant human erythropoietin may be considered, although its use in pregnant women without chronic renal failure has no indication in the prescribing information of this drug.

INTRODUCCIÓN: Introducción: la cirugía bariátrica (CB) implica déficits nutricionales y de oligoelementos que pueden tener una repercusión negativa en caso de no tratarse adecuadamente, especialmente en situaciones como la gestación. Caso clínico: paciente sometida a CB del tipo de la derivación biliopancreática, sin adherencia terapéutica posterior, que acude por edemas, confirmándose la presencia de una gestación de 29 semanas (feto CIR de tipo I) y de anemia moderada. Se reinició la suplementación de vitaminas, oligoelementos, nutrición enteral y hierro intravenoso (FEIV). Debido a la escasa respuesta de la hemoglobina con depósitos de hierro repletados, se asoció eritropoyetina humana recombinante (rHuEPO). Discusión: los déficits nutricionales más frecuentes tras una CB malabsortiva son la ferropenia y la hipoproteinemia. La ferropenia y la anemia incrementan el riesgo del parto pretérmino, el bajo peso y la mortalidad perinatal. En las pacientes sin adecuada respuesta al FEIV puede plantearse el tratamiento con rHuEPO, aunque su uso en gestantes sin insuficiencia renal crónica no dispone de indicación en la ficha técnica.

Primary eosinophilic gastroenteritis: A case series from western India.

Primary eosinophilic gastroenteritis is a rare inflammatory disorder of gastrointestinal tract characterized by symptoms like abdominal pain, diarrhea, vomiting, weight loss, and eosinophilic infiltration of the intestinal wall with or without peripheral eosinophilia. We found four cases with different causes of eosinophilic enteritis with varying manifestations ranging from chronic diarrhea with malabsorption, dysphagia, and gastric outlet obstruction due to mass-like lesions.

Revisión del manejo del síndrome diarreico después de una cirugía bariátrica / Review of the management of diarrhea syndrome after a bariatric surgery

La obesidad es un problema de salud frecuente en nuestra población. La cirugía bariátrica es el tratamiento de elección en los casos graves, es muy efectiva (junto con una adecuada modificación de los hábitos de vida), pero también se asocia a múltiples efectos secundarios. Uno de los más frecuentes y que puede reducir marcadamente la calidad de vida es la diarrea. La diarrea que aparece posterior a una cirugía bariátrica puede ser de distintas causas y mecanismos fisiopatogénicos que van a depender, en parte, del tipo de cirugía realizada. Las causas más frecuentes son el síndrome de dumping, la diarrea por vagotomía, el síndrome de intestino corto, la malabsorción de hidratos de carbono, la malabsorción proteica, las alteraciones de la microbiota, la infección por Clostridium difficile, el sobrecrecimiento bacteriano, la malabsorción de sales biliares, la insuficiencia pancreática, trastornos endocrinológicos, trastornos adictivos y otros trastornos digestivos no necesariamente relacionados con la cirugía

Obesity is a prevalent health problem in our population. Bariatric surgery is the indicated treatment for severe cases. It is very effective (together with an adequate lifestyle modification) but it is also associated with frequent adverse events. One of the most frequent and disturbing adverse event is diarrhea. Diarrhea after bariatric surgery may be secondary to multiple causes and the physiopathogenic mechanisms may depend on the type of surgery performed. The most frequent diarrhea mechanisms are dumping syndrome, vagotomy, short bowel syndrome, carbohydrate malabsorption, protein malabsorption, alterations of the microbiota, Clostridium difficile infection, bacterial overgrowth, bile salt malabsorption, pancreatic insufficiency, endocrinological disorders, addictive disorders, and other digestive disorders not necessarily related to surgery