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.

Abstract White kidney bean extract (WKBE) is a nutraceutical often advocated as an anti-obesity agent. The main proposed mechanism for these effects is alpha-amylase inhibition, thereby slowing carbohydrate digestion and absorption. Thus, it is possible that WKBE could impact the gut microbiota and modulate gut health. We investigated the effects of supplementing 20 healthy adults with WKBE for 1 week in a randomised, placebo-controlled crossover trial on the composition of the gut microbiota, gastrointestinal (GI) inflammation (faecal calprotectin), GI symptoms, and stool habits. We conducted in vitro experiments and used a gut model system to explore potential inhibition of alpha-amylase. We gained qualitative insight into participant experiences of using WKBE via focus groups. WKBE supplementation decreased the relative abundance of Bacteroidetes and increased that of Firmicutes, however, there were no significant differences in post-intervention gut microbiota measurements between the WKBE and control. There were no significant effects on GI inflammation or symptoms related to constipation, or stool consistency or frequency. Our in vitro and gut model system analyses showed no effects of WKBE on alpha-amylase activity. Our findings suggest that WKBE may modulate the gut microbiota in healthy adults, however, the underlying mechanism is unlikely due to active site inhibition of alpha-amylase.

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.

Background: Satiety in the stomach is often caused by distension and the satiating feeling is triggered through afferent vagal signals. Increasing or prolonging the distension of the stomach with a low-calorie agent would be beneficial in reducing the energy intake and potentially aid in the management of weight. The aim of this work was to quantify the rheological properties of an alginate formulation to induce satiety (AFIS) as it passes through a physiologically relevant model of human digestive tract. Methods: A physiologically relevant model of oral, gastric and small intestinal digestion was used to simulate in vivo conditions, including digestive capacity and physical forces. Samples were taken from the model and the rheological properties and viscosity of them assessed. This was repeated in the presence of a mixed meal. Results: The addition of the AFIS gelled strongly in the gastric phase of the model gut system and reformed the gel after shear stress disrupted the gel network. The inclusion of the formulation to induce satiety with a mixed meal to the model gut system increased the viscosity in the gastric phase to a greater extent than just the formulation alone. Conclusions: The forces generated by the stomach in vivo would be sufficient to eventually overcome the gelled formulation and with the repeated breakdown and additional gastric secretions would eventually allow passage into the small intestine. The synergistic increase in viscosity seen with the mixed meal and the formulation indicated an interaction between the formulation and the meal. The AFIS would potentially increase the retention time of gastric contents as well as gelling strongly. However, the forces generated by the stomach in vivo would eventually be sufficient to breakdown the formulation, and with the additional gastric secretion, allow it to pass into the small intestine, avoiding indefinite retention.

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.

This review discusses the utility and limitations of model gut systems in accurately modelling the mucosa of the digestive tract from both an anatomical and functional perspective, with a particular focus on the oesophagus and the upper digestive tract, and what this means for effective in vitro modelling of oesophageal pathology. Disorders of the oesophagus include heartburn, dysphagia, eosinophilic oesophagitis, achalasia, oesophageal spasm and gastroesophageal reflux disease. 3D in vitro models of the oesophagus, such as organotypic 3D culture and spheroid culture, have been shown to be effective tools for investigating oesophageal pathology. However, these models are not integrated with modelling of the upper digestive tract—presenting an opportunity for future development. Reflux of upper gastrointestinal contents is a major contributor to oesophageal pathologies like gastroesophageal reflux disease and Barratt’s oesophagus, and in vitro models are essential for understanding their mechanisms and developing solutions. The limitations of current model gut systems in modelling the mucosa is not only limited to the oesophagus. Integration of modelling of the mucus covered epithelia of the stomach and small intestine in to upper digestive tract models is limited and often not considered at all. In this paper we discuss mucus structure and function and current approaches to modelling of the mucus layer in isolation, and in integrated systems with cell culture systems and digestive models. We identify a need for relevant modelling of the viscoelastic properties of mucus and its protective function to allow complete integration in modelling. Addressing limitations of current in vitro models and integrating upper gastrointestinal models with those of the oesophagus presents an opportunity for better understanding oesophageal physiology and pathophysiology where reflux of digestive fluids is involved.