Biological activity of alginate and its effect on pancreatic lipase inhibition as a potential treatment for obesity

Alginates are classed as a dietary fibre and have been shown to inhibit digestive enzymes in vitro, and therefore could be used as an obesity treatment. The current study aims to assess whether alginate in a bread vehicle maintains its inhibition properties despite cooking and digestion, and may therefore be used as a potential treatment for obesity. After 180 min in a model gut that replicates digestion in the mouth, stomach and small intestines alginate bread (AB), control bread (CB), CB with Manucol® DM alginate, free DM alginate and model gut solution were collected. DM, LFR 5/60 and SF200 were heated at 37 °C and 200 °C, with DM also heated at 50, 100 and 150 °C. Samples from the model gut and heated alginate were assessed for molecular size and inhibition properties using viscosity, gel filtration and a lipase turbidity assay. AB does not significantly increase viscosity in the model gut. Viscosity of alginate reduces beyond 100 °C, although alginate retains its inhibition properties up to 150 °C. Cooking into the bread does not reduce the molecular size of the alginate or affect its inhibition properties. These data demonstrate the robustness of alginates lipase inhibition despite the cooking process and digestion. Therefore adding alginate to a bread vehicle may have the potential in the treatment for obesity

Acceptability of alginate enriched bread and its effect on fat digestion in humans

Lifestyle interventions and physical activity remain the cornerstone of obesity management, as pharmacological therapies (orlistat) are associated with gastrointestinal (GI) side effects. Combining orlistat with fibers can reduce side effects, improving compliance. Therefore, a fiber that inhibits lipase without side effects could help treat obesity. The aims of the present work were to assess whether alginate enriched bread could inhibit fat digestion, and assess the acceptability of alginate bread and its effect on GI wellbeing. A double-blind, randomised, controlled cross-over pilot study (NCT03350958) assessed the impact of an alginate bread meal on; lipid content in ileal effluent and circulating triacylglycerol levels. This was compared against the same meal with non-enriched (control) bread. GI wellbeing and acceptability of alginate bread was compared to control bread through daily wellbeing questionnaires and food diaries (NCT03477981). Control bread followed by alginate bread were consumed for two weeks respectively. Consumption of alginate bread reduced circulating triacylglycerol compared to control (2% reduction in AUC) and significantly increased lipid content in ileal effluent (3.8 g ± 1.6 after 210 min). There were no significant changes to GI wellbeing when comparing alginate bread to control bread. A significant increase in the feeling of fullness occurred with alginate bread compared to baseline and the first week of control bread consumption. This study showed that sustained consumption of alginate enriched bread does not alter GI wellbeing and can decrease lipolysis, increasing lipid leaving the small intestine. Further studies are required to demonstrate that reduced fat digestion through the action of alginate can reduce fat mass or body weight

Pepsin properties, structure, and its accurate measurement: a narrative review

Pepsin is an aspartate protease that is generated from its proenzyme, pepsinogen by autocatalysis initiated by a fall in pH below 5. Human gastric juice contains eight isoenzymes of pepsin. The peptides released on conversion of pepsinogen to pepsin of which there are potentially five, have been shown to have antimicrobial activity against a wide range of bacteria including Escherichia coli, Pseudomonas and Staphylococcus which have also been shown to have biofilm formation inhibiting properties. The stability in response to changes in pH varies between pepsin and pepsinogen. Pepsinogen is stable up to pH 10, pepsin is only stable to pH just above 7.0 and is completely denatured at pH 8.0. Many diseases of the aerodigestive tract have been linked to reflux and the presence of pepsin. Therefore, the measurement of pepsin in tissue and lavages or in saliva or sputum, could be a good screening tool for the diagnosis of reflux related disease. However, there is no current consensus as to the best methods to measure it or the best time to sample it. For an effective pepsin ELISA, the following is required; a monoclonal/monospecific polyclonal antibody with a good lowest level of detection (LLOD) and sensitivity 1–25 ng/mL (depending on dilution) and an adequate supply of purified human pepsin as a standard for antibody-based assays. If possible, an activity assay for pepsin should also be used as the presence of pepsin protein does not indicate it is capable of damaging activity. Finally, if pepsin is associated with a disease large studies are required to confirm it with multiple samples. This review deals with several studies where pepsin quantitation is attempted, and their measurement techniques assessed

Prominent members of the human gut microbiota express endo-acting O-glycanases to initiate mucin breakdown

Epithelial cells that line the gut secrete complex glycoproteins that form a mucus layer to protect the gut wall from enteric pathogens. Here, the authors provide a comprehensive characterisation of endo-acting glycoside hydrolases expressed by mucin-degrading members of the microbiome that are able to cleave the O-glycan chains of a range of different animal and human mucins

Dietary fibre and weight loss: Where are we now?

“Dietary fibre” represents a wide spectrum of polysaccharides that escape digestion in the human gastrointestinal tract. The term has been widely associated with positive health outcomes, with the fibre content of food products being a potential basis for nutritional composition claims in many parts of the world. The current review aims to evaluate the current evidence from human trials on the impact of fibre-rich foods and isolated dietary fibre on body weight management. Evidence from observational studies consistently demonstrates that habitual increased intake of fruits, vegetables and whole grains is associated with lower body weight increase over time. Adherence to healthier dietary templates (including incorporation of higher amounts of plant-based foods) in intervention studies also tend to evidence greater weight loss than control diets. This further highlights the importance of fruits, vegetables and whole grains as the foundation of positive dietary habit. In contrast, randomised, controlled trials based on increase of fruit/vegetable or wholegrain food intake alone tend to show no impact on body weight or body fat outcomes, suggesting either that the length of previous studies is not long enough to observe measurable effects or that such dietary changes alone do not benefit these outcomes. While individual intervention studies suggest potential benefits of some fibre isolates on weight loss, there only appears to be reproducible evidence of efficacy for glucomannan. The limited amount of available evidence suggests a need for further, well-designed and appropriately targeted intervention studies in the future

Starch digestion in the upper gastrointestinal tract of humans

Starch provides a large proportion of the dietary energy consumed worldwide. The breakdown of dietary starch is driven by α‐amylase produced by the salivary glands and pancreatic acini and is completed by a range of brush‐border bound enzymes. This enzymatic digestion is aided by mechanical and secretory actions of the gastrointestinal tract. The absorption of the resultant glucose in the small intestine is primarily driven by two separate transport proteins − SGLT1 and GLUT2. The control of processes that govern starch digestion is complex and still not fully understood, although it appears that the human gut has the ability to sense both glucose and non‐sweet glucose oligomers. Recent work has also suggested that variations in the genes encoding for α‐amylase also appear to be associated with health outcomes. The authors consider the physiological factors that govern starch digestion and absorption, consider other dietary factors that may impact on this process and attempt to highlight the limitations in current knowledge to help focus future research needs in relation to starch digestion the upper gastrointestinal tract

The impact of dietary fibres on the physiological processes of the large intestine

No endogenous secretion of digestive enzymes occurs within the human large intestine, yet this region of the gut still has an important role in the absorption of water and a range of nutrients. In parallel, the large intestine must also cope with a high load of micro-organisms and an increasing concentration of potentially toxic agents. The duality of these roles (facilitating absorption while effectively partitioning damaging luminal agents) is vital to the proper functioning of the large intestine. The effectors of these roles are the smooth muscle that drives a complex motility and the epithelial lining. The epithelium is arranged in crypts that contain a variety of different cell types whose roles help effect absorption, protection and self-maintenance of the large intestinal epithelium. Digesta remains within the large intestine for much longer than other gastrointestinal compartments and so the composition of the luminal contents may have a greater potential to positively or negatively impact on gastrointestinal and systemic health. The current review aims to consider recent evidence that dietary fibres may impact on the physiological processes of the large intestine, with particular reference to the interplay of fibres with the resident microbiota

A Pilot Pre and Post 4 Week Intervention Evaluating the Effect of a Proprietary, Powdered, Plant Based Food on Micronutrient Status, Dietary Intake, and Markers of Health in a Healthy Adult Population

Background: A “balanced, adequate, and varied diet” is recommended as the basis of nutritionally sound diet by the World Health Organisation and national public health agencies. Huel is a proprietary, on-the-go, powdered, plant based food, providing all 26 essential vitamins and minerals, protein, essential fats, carbohydrate, fibre, and phytonutrients. Objectives: Assessing the effect of solely consuming Huel on micronutrient status, dietary intake and markers of health was achieved through a 4-week intervention of solely Huel powder. Methods: Habitual energy intake was assessed through a one-week lead in period with healthy adult participants (aged 18 or over) logging their food intake, after which only Huel was consumed for 4 weeks. Blood samples and body composition was assessed before and after the lead in week as well the end of the intervention. Thirty participants were recruited with 20 (11 females, median age 31, range 22–44) completing the study, 19 sets of blood samples were collected. 22 blood markers were analysed along with weight, BMI, waist circumference, visceral adipose tissue (VAT), and body composition. All blood micronutrients, except for Thyroid Stimulating Hormone and choline were sent to Royal Victoria Infirmary NHS, Newcastle Laboratory (Newcastle upon Tyne, United Kingdom) for analysis. Results: Fourteen of the parameters significantly changed over the course of the study with circulating haemoglobin, iron, vitamins B12 and D as well as selenium significantly increasing (p < 0.05). HbA1c, total and non-HDL cholesterol, vitamins A and E, potassium, BMI, VAT, and waist circumference all significantly decreased (p < 0.05) post intervention. Conclusion: Although energy intake decreased during the intervention period, the adherence to recommended micronutrient intake, as quantified by the dietary Total Adherence Score, significantly increased which tallies with the preservation or improvement of micronutrient status. This study potentially demonstrates that consuming only Huel for 4 weeks does not negatively affect micronutrient status

The <i>MUC2</i> Gene Product: Polymerisation and Post-Secretory Organisation—Current Models

MUC2 mucin, the primary gel-forming component of intestinal mucus, is well researched and a model of polymerisation and post-secretory organisation has been published previously. Recently, several significant developments have been made which either introduce new ideas or challenge previous theories. New ideas include an overhaul of the MUC2 C-terminal globular structure which is proposed to harbour several previously unobserved domains, and include a site for an extra intermolecular disulphide bridge dimer between the cysteine 4379 of adjacent MUC2 C-termini. MUC2 polymers are also now thought to be secreted attached to the epithelial surface of goblet cells in the small intestine and removed following secretion via a metalloprotease meprin β-mediated cleavage of the von Willebrand D2 domain of the N-terminus. It remains unclear whether MUC2 forms intermolecular dimers, trimers, or both, at the N-termini during polymerisation, with several articles supporting either trimer or dimer formation. The presence of a firm inner mucus layer in the small intestine is similarly unclear. Considering this recent research, this review proposes an update to the previous model of MUC2 polymerisation and secretion, considers conflicting theories and data, and highlights the importance of this research to the understanding of MUC2 mucus layers in health and disease