Study links collagen peptides to improved bone health in runners

Conventional pharmacological studies on spices have traditionally focused on secondary metabolites like polyphenols, alkaloids, and terpenes. More recently, food science research has also examined spice proteins and their enzymatic hydrolysates, using proteomic methods such as liquid chromatography–tandem mass spectrometry (LC-MS/MS) to identify short bioactive peptide sequences released from larger precursor proteins.6 Once released during food processing, fermentation, or gastrointestinal digestion, these functional peptides can act as metabolic regulators, antimicrobials, or antioxidants.1 Functional peptides refer to specific protein fragments that, once released from their parent proteins, exert biological activities.1,2 In the context of foods, these activities are most often demonstrated using in vitro biochemical or cell-based assays, and their physiological relevance depends on bioavailability and dose.2 Unlike intact proteins, which can have the potential to be allergenic or difficult to absorb due to their complex tertiary structures, functional peptides may exhibit improved bioaccessibility, and some small peptides can cross the intestinal epithelial barrier via peptide transport systems. However, absorption efficiency varies substantially by peptide sequence and digestive conditions.6 Nutriomics and mechanistic investigations have established that the bioactivity of a peptide is dictated by its physicochemical properties, particularly its amino acid composition, molecular weight, and net charge. For example, the presence of hydrophobic amino acids like proline, leucine, and valine often correlates with high antioxidant and enzyme-inhibitory activity.2,3 Smaller peptides, typically those less than three kilodaltons (kDa) in size, exhibit greater stability against proteolytic degradation in the gastrointestinal tract.3 Moreover, cationic peptides are particularly effective as antimicrobial agents through their electrostatic interactions with bacterial membranes.3

The study by Williams was looking for variations in hemoglobin, the oxygen-binding protein found in red blood cells. There are disorders which lead to abnormalities in hemoglobin, which can cause serious illness or even death. Identifying these variants would lead to a better prognosis for people with such abnormalities, and the study found a variant by having the ability to differentiate between leucine and isoleucine. Methylmalonic acidemia (MMA) and propionic acidemia (PA) are metabolic disorders resulting from an inability to break down isoleucine, valine, methionine, and threonine (which are also amino acids), odd-chain fatty acids, as well as cholesterol. These are rare diseases which are known as “inborn errors of metabolism” (IEM). The restriction of certain foods and the use of medical foods can form part of the treatment for IEM disorders. Leucine is added to a lot of these medical foods, and is hence selected for patients with MMA and PA. As patients with MMA and PA cannot break down isoleucine and valine, foods containing these amino acids should be avoided. However, it was previously reported that avoiding such amino acids can lead to an imbalance in the amounts of branched chain amino acids in the blood. More specifically, the ratio of leucine to isoleucine/valine was found to be increased. This could have dire consequences, potentially disrupting the synthesis of neurotransmitters due to impaired amino acid transport into the brain. In this case, it would be pivotal to distinguish between leucine and isoleucine, as the balance between these two amino acids needs to be restored to avoid potential damage.

Extensive data from the experiments have demonstrated that:

In the study, published in Scientific Reports, the researchers built on their earlier discovery of the peptide called AC253. This compound was tested in mice with AD. It was found to block the attachment of beta-amyloid to a brain cell receptor called the amylin receptor, and thus inhibit its toxic effects, as shown by an improvement in spatial memory. However, it is difficult to administer this compound because it doesn’t cross the blood-brain barrier in large amounts, and is quickly broken down in the blood. The dosage must therefore be massively increased, pushing up the amounts required for efficacy and increasing the difficulty of administration, besides enhancing the chances of an immune reaction. One way out is to convert the formulation into a pill rather than an injectable form. The complex structure of AC253 makes this difficult as well. Instead, the team devised an ingenious solution. They cleaved the compound into smaller amylin peptides, or chains of 12-14 amino acids, and tested each for its anti-amyloid activity in old mice which showed signs of AD. In this way, they found two short peptides that had the same effects as the larger compound. In particular, the researchers identified a segment that was common to both peptides, namely, SQELHRLQTY.

These seed epitopes are an exciting new addition to our understanding of oral tolerance. Scientists have already considered regulatory T cells as a promising immunotherapy route for people with severe food allergies. It may one day be possible to create regulatory T cells that are pre-programmed to tolerate certain foods and dampen immune responses to common allergens. "Diet is our most intimate interaction with our environment," says Blum. "Correctly recognizing foods as safe creates an anti-inflammatory environment to support nutrient acquisition and prevent allergy. Our research advances scientific understanding of the major dietary allergens, and points us toward future therapeutic interventions that could redirect allergic and autoimmune states." In the less-distant future, the researchers are excited to see their workflow for mapping proteins adapted to humans. The reagent they developed to track their proteins is now available for others to use, so they're hopeful that new insights into regulatory T cell-mediated oral tolerance are soon to come. Blum J. E., et al. (2026). Identification and characterization of dietary antigens in oral tolerance. Science Immunology. DOI: 10.1126/sciimmunol.aeb4684, https://www.science.org/doi/10.1126/sciimmunol.aeb4684.