PURPOSE:Superior metabolic flexibility, or the ability to efficiently switch between oxidation of carbohydrate and fat, is inversely associated with obesity and type 2 diabetes. The influence of dietary factors on metabolic flexibility is incompletely understood. This study examined the impact of dietary carbohydrate digestion rate on metabolic flexibility and metabolic substrate utilization. METHODS:We employed percent relative cumulative frequency (PRCF) analyses coupled with a new application of modeling using the Mixed Weibull Cumulative Distribution function to examine respiratory exchange ratio (RER) data from adult wild-type mice and mice lacking the mucosal maltase-glucoamylase enzyme (Mgam) under different dietary carbohydrate conditions, with diets matched for total carbohydrate contents and containing different ratios of slowly digestible starch (SDS) and resistant starch (RS), or that were high in sucrose or fat. Fungal amyloglucosidase (AMG) was administered in drinking water to increase carbohydrate digestion rate. We devised a Metabolic Flexibility Factor (MFF) to quantitate metabolic flexibility for each dietary condition and mouse genotype, with higher MFF indicating higher metabolic flexibility. RESULTS:Diets high in SDS exhibited lower average RER and higher metabolic flexibility (MFF) than diets high in resistant starch, sucrose, or fat. Diets containing high and intermediate amounts of SDS led to a more complete shift to fat oxidation. While mouse genotype had minimal effects on substrate oxidation and MFF, AMG supplementation shifted substrate utilization to carbohydrate oxidation and generally decreased MFF. CONCLUSIONS:Consumption of slowly digestible carbohydrates improved measures of metabolic substrate utilization at the whole-body level in adult mice.

Increasing the energy density of porridges could help meet the needs of moderately malnourished, stunted children. However, it is not clear whether stunted toddlers can adequately digest and obtain energy from energy-dense porridges with thick texture. A clinical study was conducted in Bamako, Mali, using 13C-labeled substrates and serial breath sampling to determine whether stunted toddlers differed from healthy toddlers in their capacity to digest thick and thin sorghum porridges. Experimental porridges, including a traditional porridge (control), a starch-enriched calorie-dense thick porridge, and an α-amylase-thinned calorie-dense porridge, were fed to stunted (n = 24) and healthy (n = 24) 18–30-month toddlers. Breath test results were expressed as Percent Dose Recovery and curve fit using the Weibull function to determine the kinetics of starch digestion. The stunted and healthy toddlers were able to digest and oxidize the starch from traditional porridge equally well, with no statistically significant differences between the kinetic parameters of the two groups. After consumption of thickened porridge, healthy toddlers had slightly faster starch digestion kinetics with PDR curves rising more rapidly (p < 0.05) and peaking earlier in the postprandial period (p < 0.01) for healthy individuals than for stunted individuals, yet these groups did not have differences in the overall extent of starch digestion, as their final CPDR values were not significantly different. Gastric emptying rate did not differ significantly between the healthy and stunted groups. Overall, we found that thick porridge supplied digestible carbohydrates to stunted and healthy toddlers, as well as thinned calorie-dense porridge.

Superior metabolic flexibility, or the ability to efficiently switch between oxidation of carbohydrate and fat, is inversely associated with obesity and type 2 diabetes. This study examined the impact of dietary carbohydrate digestion rate on metabolic substrate utilization and metabolic flexibility. We employed percent relative cumulative frequency (PRCF) analyses coupled with a new application of modeling using the Mixed Weibull Cumulative Distribution function to examine respiratory exchange ratio (RER) data from wild-type mice and mice lacking the mucosal maltase-glucoamylase enzyme (Mgam, null) under different dietary carbohydrate conditions. We further devised a Metabolic Flexibility Factor (MFF) to quantitate metabolic flexibility, with higher MFF indicating higher metabolic flexibility. The collective results indicated that a diet high in slowly digestible starch exhibited higher metabolic flexibility (MFF) than diets high in resistant starch, sucrose, or fat. These findings show a new-found benefit of consuming slowly digestible carbohydrates for improved metabolic health.

PURPOSE OF REVIEW:Disaccharidase testing, as applied to the evaluation of gastrointestinal disturbances is available but it is not routinely considered in the diagnostic work-up. The purpose of this review was to determine if disaccharidase testing is clinically useful and to consider how the results could alter patient management.RECENT FINDINGS:Indicate that carbohydrate maldigestion could contribute functional bowel disorders and negatively impact the fecal microbiome. Diagnostic techniques include enzyme activity assays performed on random endoscopically obtained small intestinal biopsies, immunohistochemistry, stable isotope tracer and nonenriched substrate load breath testing, and genetic testing for mutations. More than 40 sucrase--isomaltase gene variants coding for defective or reduced enzymatic activity have been reported and deficiency conditions are more common than previously thought.SUMMARY:The rationale for disaccharidase activity testing relates to a need to fully assess unexplained recurrent abdominal discomfort and associated symptoms. All disaccharidases share the same basic mechanism of mucosal expression and deficiency has far reaching consequences. Testing for disaccharidase expression appears to have an important role in symptom evaluation, but there are accuracy and logistical issues that should be considered. It is likely that specific recommendations for patient management, dietary modification, and enzyme supplementation would come from better testing methods.

Objectives: Maltase-glucoamylase (Mgam) and sucrase-isomaltase (Si) are mucosal alpha-glucosidases required for the digestion of starch to glucose. We hypothesized that a dietary approach to reduce Mgam and Si activities can reduce glucose generation and absorption, and improve glucose control. Methods: Rice starch was entrapped in alginate microspheres to moderate in vitro digestion properties. Three groups of 8-wk old mice (n = 8) were conditioned for 7 d with low C-13-starch-based materials differing in digestion rates (fast, slow, and slower), and then given a digestible C-13-labeled cornstarch test feeding to determine its digestion to glucose. Results: Conditioning of the small intestine with the slowly digestible starches for 7 d reduced jejunal alpha-glucosidase and sucrase activities, as well as glucose absorption for the slowly digestible starch slower group (P < 0.01). A correlative relationship was found between glucose absorption from a cornstarch test feeding given at d 7 and jejunal alpha-glucosidase and sucrase activities (R-2 = 0.64; 0.67). However, total prandial glucose levels during the 2-h feeding period did not differ. Conclusions: Decreased glucogenesis from a digestible starch feeding was found in mice conditioned on slowly digestible starch diets, suggesting that a dietary approach incorporating slowly digestible starches may change alpha-glucosidase activities to moderate glucose absorption rate. (C) 2020 Elsevier Inc. All rights reserved.

Background Disaccharides such as lactose and sucrose are sugars commonly found in human diet. They are broken down by mucosal disaccharidases in the duodenum. Previous small studies found no associations between gastrointestinal (GI) symptoms and combined low disaccharidase activity. We aim to explore the associations of low activity of disaccharidase and combinations of low activity of different disaccharidases with general GI symptom presentations in a large cohort of pediatric patients. Methods We examined a cohort (0–21 yrs.) who have undergone esophagogastroduodenoscopy and received disaccharidase activity assay from duodenal biopsy in the time period 2010 to 2012. Disaccharidase assays tested for activity of lactase, sucrase, maltase, and palatinase. GI symptoms were grouped into four categories, abdominal pain, diarrhea, weight loss, and gastroesophageal reflux. Results Of the 347 subjects, we found an association between low lactase activity and abdominal pain (OR = 1.78; 95% CI = 1.07–2.97; p < 0.05). Subjects with a lactase/sucrase ratio < 0.2 were found to be associated with abdominal pain (OR = 2.25; 95% CI = 1.25–4.04; p < 0.05), Subjects with low pandisaccharidase may be correlated with abdominal pain and have a unique frequency of GI symptoms due to low frequency of diarrhea and weight loss, but they were not statistically significant. Conclusions Low activities of certain disaccharidase combinations may be associated with GI symptoms in subjects; a prospective study may be needed to investigate further.

Human breath is an easily, noninvasively obtained substance. It offers insight into metabolism and is used to diagnose disaccharide malabsorption, infection, small bowel bacterial over growth, and transit times. Herein, we discuss the readily available clinical breath tests, how they function, how they are administered and interpreted and some pitfalls in their use.

BACKGROUND AND AIMS:Intestinal adaptation in short bowel syndrome (SBS) includes morphologic processes and functional mechanisms. This study investigated whether digestive enzyme expression in the duodenum and colon is upregulated in SBS patients.METHOD:Sucrase-isomaltase (SI), lactase-phlorizin hydrolase (LPH), and neutral Aminopeptidase N (ApN) were analyzed in duodenal and colonic biopsies from nine SBS patients in a late stage of adaptation as well as healthy and disease controls by immunoelectron microscopy (IEM), Western blots, and enzyme activities. Furthermore, proliferation rates and intestinal microbiota were analyzed in the mucosal specimen.RESULTS:We found significantly increased amounts of SI, LPH, and ApN in colonocytes in most SBS patients with large variation and strongest effect for SI and ApN. Digestive enzyme expression was only partially elevated in duodenal enterocytes due to a low proliferation level measured by Ki-67 staining. Microbiome analysis revealed high amounts of Lactobacillus resp. low amounts of Proteobacteria in SBS patients with preservation of colon and ileocecal valve. Colonic expression was associated with a better clinical course in single cases.CONCLUSION:In SBS patients disaccharidases and peptidases can be upregulated in the colon. Stimulation of this colonic intestinalization process by drugs, nutrients, and pre- or probiotics might offer better therapeutic approaches.

episodes (p> 0.88), number of pH only episodes (p>0.47),proximal BCT (p>0.32) or distal BCT (p>0.25).Conclusions: Reflux testing cannot predict which patients will have the greatest disability from their symptoms.Greater reflux burden on pH-MII testing is not associated with worse QOL.Children who have symptomatic improvement with a PPI trial have better QOL scores. Tu1305

F or human infants, supplementation of maternal nursing is called complementary feeding or beikost. The German word beikost translates as ‘‘infant foods other than milk or formula.’’ Starchy foods are the first offered in most cultures. The introduction of beikost begins the weaning process and introduces environmental vectors stressing the maternal-infant dyad. The presently recommended age for introduction of complementary feedings to the suckling infant is six months. One argument offered by learned committees for this recommendation is that amylase production and secretion in normal infants is physiologically delayed. Pediatricians worldwide, however, know that many mothers begin offering solids in the first months of life and that this common practice is usually rewarded by positive infant behavior. On the other hand, it is believed that in developing countries, stunting of infant growth might be due to nutritional quality and environmental contamination of complementary feedings. Studies of starch feeding show that both whole cereal starch and maltodextrin are digested and absorbed by the young infant. Feeding studies of nursing infants

Dietary starch is finally converted to glucose for absorption by the small intestine mucosal α-glucosidases (sucrase-isomaltase [SI] and maltase-glucoamylase), and control of this process has health implications. Here, the molecular mechanisms were analyzed associated with starch-triggered maturation and transport of SI. Biosynthetic pulse-chase in Caco-2 cells revealed that the high MW SI species (265 kDa) induced by maltose (an α-amylase starch digestion product) had a higher rate of early trafficking and maturation compared with a glucose-induced SI (245 kDa). The maltose-induced SI was found to have higher affinity to lipid rafts, which are associated with enhanced targeting to the apical membrane and higher activity. Accordingly, in situ maltose-hydrolyzing action was enhanced in the maltose-treated cells. Thus, starch digestion products at the luminal surface of small intestinal enterocytes are sensed and accelerate the intracellular processing of SI to enhance starch digestion capacity in the intestinal lumen.-Chegeni, M., Amiri, M., Nichols, B. L., Naim, H. Y., Hamaker, B. R. Dietary starch breakdown product sensing mobilizes and apically activates α-glucosidases in small intestinal enterocytes.

BACKGROUND:A subset of children with functional gastrointestinal disorders (FGIDs), which includes functional dyspepsia, may have duodenal disaccharidase deficiencies.OBJECTIVES:To determine the frequency, demographics, and clinical characteristics associated with duodenal disaccharidase deficiencies in children with functional dyspepsia.METHODS:Children ages 4 to 18 years undergoing esophagogastroduodenoscopy (EGD) evaluation for dyspepsia were enrolled in either a retrospective (study 1) or prospective (study 2) evaluation. Those with histologic abnormalities were excluded. Duodenal biopsies were obtained for disaccharidase enzyme analysis. In the retrospective study, both demographic and clinical characteristics were obtained via chart review. In the prospective study, parents completed the Rome II Questionnaire on Gastrointestinal Symptoms before the EGD.RESULTS:One hundred and twenty-nine children (n = 101, study 1; n = 28, study 2) were included. Mean age was 11.2 ± 3.8 (SD) years in study 1 and 10.6 ± 3.2 years in study 2. Forty-eight (47.5%) of subjects in study 1 and 13 (46.4%) of subjects in study 2 had at least 1 disaccharidase deficiency identified. All of those with a disaccharidase deficiency in both studies had lactase deficiency with 8 (7.9%) and 5 (17.9%) of those in studies 1 and 2, respectively, having an additional disaccharidase deficiency. The second most common disaccharidase deficiency pattern was that of pan-disaccharidase deficiency (PDD) in both studies. In study 1 (where both race and ethnicity were captured), self-identified Hispanic (vs non-Hispanic, P < 0.05) and non-white (vs white, P < 0.01) children were more likely to have lactase deficiency. Age, sex, and type of gastrointestinal symptom were not associated with presence or absence of a disaccharidase deficiency.CONCLUSIONS:Approximately half of children with functional dyspepsia undergoing EGD were identified as having a disaccharidase deficiency (predominantly lactase deficiency). Race/ethnicity may be associated with the likelihood of identifying a disaccharidase deficiency. Other clinical characteristics were not able to distinguish those with versus without a disaccharidase deficiency.

From anecdotal evidence that traditional African sorghum and millet foods are filling and provide sustained energy, we hypothesized that gastric emptying rates of sorghum and millet foods are slow, particularly compared to non-traditional starchy foods (white rice, potato, wheat pasta). A human trial to study gastric emptying of staple foods eaten in Bamako, Mali was conducted using a carbon-13 (13C)-labelled octanoic acid breath test for gastric emptying, and subjective pre-test and satiety response questionnaires. Fourteen healthy volunteers in Bamako participated in a crossover design to test eight starchy staples. A second validation study was done one year later in Bamako with six volunteers to correct for endogenous 13C differences in the starches from different sources. In both trials, traditional sorghum and millet foods (thick porridges and millet couscous) had gastric half-emptying times about twice as long as rice, potato, or pasta (p < 0.0001). There were only minor changes due to the 13C correction. Pre-test assessment of millet couscous and rice ranked them as more filling and aligned well with postprandial hunger rankings, suggesting that a preconceived idea of rice being highly satiating may have influenced subjective satiety scoring. Traditional African sorghum and millet foods, whether viscous in the form of a thick porridge or as non-viscous couscous, had distinctly slow gastric emptying, in contrast to the faster emptying of non-traditional starchy foods, which are popular among West African urban consumers.

Background and Hypotheses: Human starch digestion is a multienzyme process involving 6 different enzymes: salivary and pancreatic a-amylase; sucrase and isomaltase (from sucrose-isomaltase [SI]), and maltase and glucoamylase (from maltase-glucoamylase [MGAM]). Together these enzymes cleave starch to smaller molecules ultimately resulting in the absorbable monosaccharide glucose. Approximately 80% of all mucosal maltase activity is accounted for by SI and the reminder by MGAM. Clinical studies suggest that starch may be poorly digested in those with congenital sucrase-isomaltase deficiency (CSID). Poor starch digestion occurs in individuals with CSID and can be documented using a noninvasive C-13-breath test (BT). Methods: C-13-Labled starch was used as a test BT substrate in children with CSID. Sucrase deficiency was previously documented in study subjects by both duodenal biopsy enzyme assays and C-13-sucrose BT. Breath (CO2)-C-13 was quantitated at intervals before and after serial C-13-substrate loads (glucose followed 75minutes later by starch). Variations in metabolism were normalized against C-13-glucose BT (coefficient of glucose absorption). Control subjects consisted of healthy family members and a group of children with functional abdominal pain with biopsy-proven sucrase sufficiency. Results: Children with CSID had a significant reduction of C-13-starch digestion mirroring that of their duodenal sucrase and maltase activity and C-13-sucrase BT. Conclusions: In children with CSID, starch digestion may be impaired. In children with CSID, starch digestion correlates well with measures of sucrase activity.

The mucosal maltase enzymes are characterized by an activity that produces glucose from linear glucose polymers, assayed with the disaccharide maltose. The related enzyme isomaltase produces glucose from branched glucose polymers, assayed with palatinose. Maltase and isomaltase activities are part of the 4 disaccharidases assayed from clinical duodenal biopsy homogenates. The reported maltase activities are more difficult to interpret than lactase or sucrase activities because both the sucrase-isomaltase and maltase-glucoamylase proteins have overlapping maltase activities. The early work of Dahlqvist identified 4 maltase activities from human small intestinal mucosa. On one peptide, sucrase (maltase Ib) and isomaltase (maltase Ia) activities shared maltase activities but identified the enzymes as sucrase-isomaltase. On the other peptide, no distinguishing characteristics of the 2 maltase activities (maltases II and III) were detected and the activities identified as maltase-glucoamylase. The nutritional/clinical importance of small intestinal maltase and isomaltase activities are due to their crucial role in the digestion of food starches to absorbable free glucose. This review focuses on the interpretation of biopsy maltase activities in the context of reported lactase, sucrase, maltase, and palatinase biopsy assay activity patterns. We present a classification of mucosal maltase deficiencies and novel primary maltase deficiency (Ib, II, III) and provide a clarification of the role of maltase activity assayed from clinically obtained duodenal biopsies, as a path toward future clinical and molecular genomic investigations.

ABSTRACTBackground and Objective:Although named because of its sucrose hydrolytic activity, this mucosal enzyme plays a leading role in starch digestion because of its maltase and glucoamylase activities. Sucrase‐deficient mutant shrews, Suncus murinus, were used as a model to investigate starch digestion in patients with congenital sucrase‐isomaltase deficiency. Starch digestion is much more complex than sucrose digestion. Six enzyme activities, 2 α‐amylases (Amy), and 4 mucosal α‐glucosidases (maltases), including maltase‐glucoamylase (Mgam) and sucrase‐isomaltase (Si) subunit activities, are needed to digest starch to absorbable free glucose. Amy breaks down insoluble starch to soluble dextrins; mucosal Mgam and Si can either directly digest starch to glucose or convert the post‐α‐amylolytic dextrins to glucose. Starch digestion is reduced because of sucrase deficiency and oral glucoamylase enzyme supplement can correct the starch maldigestion. The aim of the present study was to measure glucogenesis in suc/suc shrews after feeding of starch and improvement of glucogenesis by oral glucoamylase supplements.Methods:Sucrase mutant (suc/suc) and heterozygous (+/suc) shrews were fed with 13C‐enriched starch diets. Glucogenesis derived from starch was measured as blood 13C‐glucose enrichment and oral recombinant C‐terminal Mgam glucoamylase (M20) was supplemented to improve starch digestion.Results:After feedings, suc/suc and +/suc shrews had different starch digestions as shown by blood glucose enrichment and the suc/suc had lower total glucose concentrations. Oral supplements of glucoamylase increased suc/suc total blood glucose and quantitative starch digestion to glucose.Conclusions:Sucrase deficiency, in this model of congenital sucrase‐isomaltase deficiency, reduces blood glucose response to starch feeding. Supplementing the diet with oral recombinant glucoamylase significantly improved starch digestion in the sucrase‐deficient shrew.

Diverse natural phenolic compounds show inhibition activity of intestinal α-glucosidases, which may constitute the molecular basis for their ability to control systemic glycemia. Additionally, phenolics can modify mRNA expression for proteins involved in nutritional, metabolic or immune processes. To explore the possibility that phenolics can regulate the mRNA expression, enzymatic activity, and protein synthesis/processing of intestinal Maltase-Glucoamylase (MGAM) and Sucrase-Isomaltase (SI), small intestinal explants from Balb/c mice were cultured for 24 h in the presence or absence of gallic acid, caffeic acid, and (+)-catechin at 0.1, 0.5, and 1 mM. We measured the levels of MGAM and SI mRNA expression by qRT-PCR, maltase and sucrase activities by a standard colorimetric method and the molecular size distribution of MGAM and SI proteins by western blotting. mRNA expression for MGAM was induced by the three phenolic compounds at 0.1 mM. mRNA expression for SI was induced by caffeic and gallic acids, but not by (+)-catechin. Caffeic acid was the most effective inducer of mRNA expression of these enzymes. Total maltase and sucrase activities were not affected by treatment with phenolics. The proportion of high molecular size forms of MGAM was significantly increased by two of the three phenolic compounds, but little effect was observed on SI proteins. Thus, changes in the protein synthesis/processing, affecting the proportions of the different molecular forms of MGAM, may account for the lack of correlation between mRNA expression and enzymatic activity.

Digestible glycemic carbohydrates are an important energy source to support the rapid growth and development of young children. The aim of this comprehensive review is to present up‐to‐date knowledge of starch digestion in the young child. Starchy foods are consumed uncooked (e.g., fruit or vegetable salad) or cooked (e.g., mashed potato), and in granule (insoluble) or gelatinized (soluble) forms. Various aspects of digestive enzymes in the young child are described, including pancreatic α‐amylase deficiency and the existence of salivary α‐amylase, milk α‐amylase, blood α‐amylase, and α‐glucosidases. The young child can digest starchy foods and absorb dietary glucose. Among the various sources of starches, rice maltodextrin is most digestible because of its unique structural characteristics. Common sources of complementary starches are also described. This review would benefit the food industry in designing complementary foods (also known as beikost), and also health providers, such as pediatricians and dietitians in understanding starch digestion and the difference between granule and gelatinized starch.