Simulating human digestion: developing our knowledge to create healthier and more sustainable foods

The gold standard for nutrition studies is clinical trials but they are expensive and variable, and do not always provide the mechanistic information required, hence the increased use of in vitro and increasingly in silico simulations of digestion. In this review, we give examples of the main simulations being used to model upper gastrointestinal tract digestion. This review ranges from the selection of enzymes to the interpretation of results from static models to fully dynamic models. We describe the modifications made to accommodate different demographic groups (infants, the elderly, etc.). We list examples of the application of the different models as well as giving the advantages and disadvantages. A model is only useful if it predicts or aids the understanding of physiological behaviour. Thus, the final section of the review makes a comparison of results obtained from experiments undertaken using in vitro simulations with those obtained in vivo. This comparison will help the reader understand the appropriateness of each model for the type of measurement to be undertaken. In particular, human studies tend to measure bioactive concentrations in blood and not in the gastrointestinal tract whereas in vitro studies often only produce data on release of nutrients into the gut lumen. This is the difficulty of comparing bioaccessibility as generated in vitro with bioavailability as generated in vivo. It is apparent that the models being used are increasingly being validated with in vivo data and this bodes well for the future

Bile salts in digestion and transport of lipids

Because of their unusual chemical structure, bile salts (BS) play a fundamental role in intestinal lipid digestion and transport. BS have a planar arrangement of hydrophobic and hydrophilic moieties, which enables the BS molecules to form peculiar self-assembled structures in aqueous solutions. This molecular arrangement also has an influence on specific interactions of BS with lipid molecules and other compounds of ingested food and digestive media. Those comprise the complex scenario in which lipolysis occurs. In this review, we discuss the BS synthesis, composition, bulk interactions and mode of action during lipid digestion and transport. We look specifically into surfactant-related functions of BS that affect lipolysis, such as interactions with dietary fibre and emulsifiers, the interfacial activity in facilitating lipase and colipase anchoring to the lipid substrate interface, and finally the role of BS in the intestinal transport of lipids. Unravelling the roles of BS in the processing of lipids in the gastrointestinal tract requires a detailed analysis of their interactions with different compounds. We provide an update on the most recent findings concerning two areas of BS involvement: lipolysis and intestinal transport. We first explore the interactions of BS with various dietary fibres and food emulsifiers in bulk and at interfaces, as these appear to be key aspects for understanding interactions with digestive media. Next, we explore the interactions of BS with components of the intestinal digestion environment, and the role of BS in displacing material from the oil-water interface and facilitating adsorption of lipase. We look into the process of desorption, solubilisation of lipolysis, products and formation of mixed micelles. Finally, the BS-driven interactions of colloidal particles with the small intestinal mucus layer are considered, providing new findings for the overall assessment of the role of BS in lipid digestion and intestinal transport. This review offers a unique compilation of well-established and most recent studies dealing with the interactions of BS with food emulsifiers, nanoparticles and dietary fibre, as well as with the luminal compounds of the gut, such as lipase-colipase, triglycerides and intestinal mucus. The combined analysis of these complex interactions may provide crucial information on the pattern and extent of lipid digestion. Such knowledge is important for controlling the uptake of dietary lipids or lipophilic pharmaceuticals in the gastrointestinal tract through the engineering of novel food structures or colloidal drug-delivery systems

In vitro digestibility of O/W emulsions co-ingested with complex meals: Influence of the food matrix

Oil-in-water (O/W) emulsions are promising delivery systems of lipophilic bioactive compounds into meals composed mainly of water. The colloidal stability of β-carotene-loaded O/W emulsion incorporated into whole milk, oatmeal and whole milk-oatmeal meals. Their subsequent gastric emptying rate, lipid digestibility and β-carotene retention during in vitro gastrointestinal digestion were evaluated using a semi-dynamic gastric model followed by a static small intestinal model. The dispersed particles within the meals, lipid droplets, casein micelles as well as protein and β-glucan aggregates, were responsible for the bigger average particle sizes of both O/W-oatmeal and O/W-whole milk-oatmeal (13.07 ± 1.81 and 7.60 ± 1.21 μm, respectively) compared to the O/W emulsions and O/W-whole milk (0.56 ± 0.03 and 0.44 ± 0.04 μm, respectively). Semi-dynamic in vitro gastric digestion of O/W-whole milk showed lipid droplets embedded into an insoluble protein network emptied earlier than the O/W emulsion. Conversely, O/W-oatmeal and O/W-whole milk-oatmeal had delayed lipid emptying, probably because of the gelation of the β-glucan from oats. During the in vitro small intestinal digestion, the rate of the FFA release was linked to the gastric emptying rate. Indeed, both O/W emulsion and O/W-whole milk presented an exponential increase in the FFA release, whereas the O/W-oatmeal and O/W-whole milk-oatmeal followed a stepwise trend. The β-carotene retention during in vitro gastrointestinal digestion depended on the lipid amount at each digestion time moment. Hence, this work provides valuable insight into the behaviour of O/W emulsions incorporated into meals and during their subsequent in vitro gastrointestinal digestion

Chloroplast-rich material from the physical fractionation of pea vine ( Pisum sativum ) postharvest field residue (Haulm)

An innovative procedure for plant chloroplasts isolation has been proposed, which consists of juice extraction by physical fractionation from plant material and recovery of its chloroplast-rich fraction (CRF) by centrifugation. This simple method has been applied to pea vine haulm subjected to different post-harvest treatments: blanching, storage at different relative humidity values and fermentation. Additionally, freeze storage of the extracted juice was carried out. The macronutrient (total lipids, proteins, ash and carbohydrates) and micronutrient (fatty acids, chlorophylls, β-carotene, α-tocopherol and ascorbic acid) content and composition of the CRF have been determined. The CRF isolated from fresh pea vine haulm is a potential source of essential micronutrients (α-linolenic acid, β-carotene, α-tocopherol) and carbohydrates, whereas the post-harvest treatments trialled have a detrimental effect on the nutritional content. Industrial applications for the recovered nutritionally rich fraction, such as food supplement ingredient or animal feeding, are likely envisaged, while optimising the use of green haulm

Interactions of bile salts with a dietary fibre, methylcellulose, and impact on lipolysis

Methylcellulose (MC) has a demonstrated capacity to reduce fat absorption, hypothetically through bile salt (BS) activity inhibition. We investigated MC cholesterol-lowering mechanism, and compared the influence of two BS, sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC), which differ slightly by their architecture and exhibit contrasting functions during lipolysis. BS/MC bulk interactions were investigated by rheology, and BS behaviour at the MC/water interface studied with surface pressure and ellipsometry measurements. In vitro lipolysis studies were performed to evaluate the effect of BS on MC-stabilised emulsion droplets microstructure, with confocal microscopy, and free fatty acids release, with the pH-stat method. Our results demonstrate that BS structure dictates their interactions with MC, which, in turn, impact lipolysis. Compared to NaTC, NaTDC alters MC viscoelasticity more significantly, which may correlate with its weaker ability to promote lipolysis, and desorbs from the interface at lower concentrations, which may explain its higher propensity to destabilise emulsions

Influence of the particle size of encapsulated chia oil on the oil release and bioaccessibility during <i>in vitro</i> gastrointestinal digestion

Among vegetable oils, chia oil has been gaining interest in recent years due to its high linolenic acid content (ALA, 18:3 ω3). The aim of this work was to study the influence of the particle size of encapsulated purified chia oil (PCO) on the encapsulation efficiency and PCO release during in vitro digestion. PCO micro- and nano-sized particles with sodium alginate (SA) as an encapsulating agent (ME-PCO-SA and NE-PCO-SA) were designed by micro and nano spray-drying, respectively, applying a central composite plus star point experimental design. NE-PCO-SA showed a smaller particle size and higher encapsulation efficiency of PCO than ME-PCO-SA (0.16 μm vs. 3.5 μm; 98.1% vs. 92.0%). Emulsions (NE-PCO and ME-PCO) and particles (NE-PCO-SA and ME-PCO-SA) were subjected to in vitro static gastrointestinal digestion. ME-PCO and NE-PCO showed sustained oil release throughout the three phases of digestion (oral, gastric and intestinal phases), whereas the PCO release from ME-PCO-SA and NE-PCO-SA occurred mainly in the intestinal phase, showing the suitability of sodium alginate as an intestine-site release polymer. Nano-sized particles showed a significantly higher PCO release after in vitro digestion (NE-PCO-SA, 78.4%) than micro-sized particles (ME-PCO-SA, 69.8%), and also higher bioaccessibility of individual free fatty acids, such as C18:3 ω-3 (NE-PCO-SA, 23.6%; ME-PCO-SA, 7.9%), due to their greater surface area. However, when ME-PCO-SA and NE-PCO-SA were incorporated into yogurt, the PCO release from both particle systems after the digestion of the matrix was similar (NE-PCO-SA, 58.8%; ME-PCO-SA-Y, 61.8%), possibly because the calcium ions contained in the yogurt induced partial ionic gelation of SA, impairing the PCO release. Sodium alginate spray-dried micro and nanoparticles showed great potential for vehiculation of omega-3 rich oils in the design of functional foods

The antibiotic vancomycin induces complexation and aggregation of gastrointestinal and submaxillary mucins

Vancomycin, a branched tricyclic glycosylated peptide antibiotic, is a last-line defence against serious infections caused by staphylococci, enterococci and other Gram-positive bacteria. Orally-administered vancomycin is the drug of choice to treat pseudomembranous enterocolitis in the gastrointestinal tract. However, the risk of vancomycin-resistant enterococcal infection or colonization is significantly associated with oral vancomycin. Using the powerful matrix-free assay of co-sedimentation analytical ultracentrifugation, reinforced by dynamic light scattering and environmental scanning electron microscopy, and with porcine mucin as the model mucin system, this is the first study to demonstrate strong interactions between vancomycin and gastric and intestinal mucins, resulting in very large aggregates and depletion of macromolecular mucin and occurring at concentrations relevant to oral dosing. In the case of another mucin which has a much lower degree of glycosylation (~60%) – bovine submaxillary mucin - a weaker but still demonstrable interaction is observed. Our demonstration - for the first time - of complexation/depletion interactions for model mucin systems with vancomycin provides the basis for further study on the implications of complexation on glycopeptide transit in humans, antibiotic bioavailability for target inhibition, in situ generation of resistance and future development strategies for absorption of the antibiotic across the mucus barrier

Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers

   This article reviews the efficacy and safety data of tirzepatide, a once-weekly, novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1) receptor agonist approved in the United States, the European Union, and other regions for the treatment of type 2 diabetes. All doses of tirzepatide demonstrated superiority in reducing A1C and body weight from baseline versus placebo or active comparators. The safety profile of tirzepatide was consistent with that of the GLP-1 receptor agonist class, with mild to moderate and transient gastrointestinal side effects being the most common adverse events. With clinically and statistically significant reductions in A1C and body weight without increased risk of hypoglycemia in various populations, tirzepatide has demonstrated potential as a first-in-class treatment option for many people with type 2 diabetes.</p