Erratum: Massive Gravitons as Feebly Interacting Dark Matter Candidates [Phys. Rev. Lett. 128, 081806 (2022)].

This corrects the article DOI: 10.1103/PhysRevLett.128.081806.

A comprehensive review of medium chain monoglycerides on metabolic pathways, nutritional and functional properties, nanotechnology formulations and applications in food system.

A large and growing body of literature has investigated the broad antibacterial spectrum and strong synergistic antimicrobial activity of medium chain monoglycerides (MCMs) have been widely investigated. Recently, more and more researches have focused on the regulation of MCMs on metabolic health and gut microbiota both in vivo and in vitro. The current review summarizes the digestion, absorption and metabolism of MCMs. Subsequently, it focuses on the functional and nutritional properties of MCMs, including the antibacterial and antiviral characteristics, the modulation of metabolic balance, the regulation of gut microbiota, and the improvement in intestinal health. Additionally, we discuss the most recent developments and application of MCMs using nanotechnologies in food industry, poultry and pharmaceutical industry. Additionally, we analyze recent application examples of MCMs and their nanotechnology formation used in food. The development of nanotechnology platforms facilitating molecular encapsulation and functional presentation contribute to the application of hydrophobic fatty acids and monoglycerides in food preservation and their antibacterial effectiveness. This study emphasizes the metabolic mechanisms and biological activity of MCMs by summarizing the prevailing state of knowledge on this topic, as well as providing insights into prospective techniques for developing the beneficial applications of MCMs to realize the industrialized production.

Evaluating early apoptosis-related cellular MiRNAs with an ultrasensitive electrochemiluminescence nanoplatform.

It is known that the abnormal expression of specific cellular miRNAs is closely related to cell apoptosis, and so monitoring the level change of these miRNAs can in principle be used to evaluate the process of apoptosis stimulated by drugs. Towards this goal, here we construct an ultrasensitive electrochemiluminescence (ECL) nanoplatform via the target miRNA-triggered immobilization of spherical nucleic acid enzymes (SNAzymes) onto tetrahedral DNA nanostructures on the electrode surface, which catalyzes the luminol-H2O2 reaction to output an ECL signal. This enables the sensitive and specific detection of two apoptosis-related miRNAs, miR-21 and miR-133a, with a detection limit of 33 aM. Furthermore, we employed the developed ECL nanoplatform to monitor the levels of these two miRNAs inside cancer cells stimulated by DOX, showing that the level of miR-21 decreases, while that of miR-133a increases in the early apoptotic cells. This difference highlights the distinct roles of the two target miRNAs, where miR-21 promotes the early apoptosis of cancer cells, whereas miR-133a suppresses it, providing new insight into cell physiological processes.

Proximity-Enhanced Electrochemiluminescence Sensing Platform for Effective Capturing of Exosomes and Probing Internal MicroRNAs Involved in Cancer Cell Apoptosis.

Exosomal microRNAs (miRNAs) play critical regulatory roles in many cellular processes, and so how to probe them has attracted increasing interest. Here we propose an aptamer-functionalized dimeric framework nucleic acid (FNA) nanoplatform for effective capture of exosomes and directly probing internal miRNAs with electrochemiluminescence (ECL) detection, not requiring RNA extraction in conventional counterparts. A CD63 protein-binding aptamer is tethered to one of the FNA structures, allowing exosomes to be immobilized there and release internal miRNAs after lysis. The target miRNA induces the formation of a Y-shaped junction on another FNA structure in a close proximity state, which benefits the loading of covalently hemin-modified spherical nucleic acid enzymes for enhanced ECL readout in the luminol-H2O2 system. In this facile way, the ultrasensitive detection of exosomal miR-21 from cancer cells is accomplished and then used for cell apoptosis analysis, indicating that the oncogene miR-21 negatively participates in the regulation of the apoptotic process; namely, downregulating the miR-21 level is unbeneficial for cancer cell growth.

Evaluation of meibomian gland dysfunction in type 2 diabetes with dry eye disease: a non-randomized controlled trial.

BACKGROUND: The purpose of this investigation was to evaluate the morphology and physiological function of the meibomian glands between type 2 diabetics with dry eye disease (DED) and control subjects. Doing so will help to better reveal the pathologic mechanisms of meibomian gland dysfunction (MGD) and DED in type 2 diabetes mellitus (T2DM). METHODS: Ninety subjects were divided into the following four groups: DM-DED group: T2DM patients with DED (n = 30); DM control group: DM patients without DED (n = 18); DED group: DED patients without DM (n = 26); and normal control group: normal subjects (n = 16). All participants administered the ocular surface disease index (OSDI) questionnaire, tear meniscus height (TMH), noninvasive Keratograph tear film break-up time (NIKBUT), Schirmer I test (SIT), corneal fluorescein staining (CFS), eyelid margin abnormality examinations, meibum quality and meibomian gland (MG) dropout evaluations. RESULTS: The percentage of MG dropout in the upper and lower lids was significantly higher in the DM-DED group than the DED group (P < 0.05 or P < 0.01). However, there was no significant difference in other MG parameters between these two groups. Oppositely, Significant difference was observed in all of MG parameters except MG dropout in the lower lids comparing DM group with normal controls (P < 0.05 or P < 0.01). While the SIT values decreased in the DM-DED group compared to the DED group (P < 0.05), no significant differences were found in the values of other tear parameters. CONCLUSIONS: The higher prevalence and increased severity of MGD was found in patients with both T2DM and DED compared to those only with DED. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800019939, date of registration December 9, 2018, prospectively registered.

Massive Gravitons as Feebly Interacting Dark Matter Candidates.

We detail our discovery of a chiral enhancement in the production cross sections of massive spin-2 gravitons, below the electroweak symmetry breaking scale, that makes them ideal dark matter candidates for the freeze-in mechanism. The result is independent of the physics at high scales and points toward masses in the keV-MeV range. The graviton is, therefore, a sub-MeV dark matter particle, as favored by the small scale galaxy structures. We apply the novel calculation to a Randall-Sundrum model with multiple branes, showing a significant parameter space where the first two massive gravitons saturate the dark matter relic density.

Computer-Assisted Recombination (CompassR) Teaches us How to Recombine Beneficial Substitutions from Directed Evolution Campaigns.

A main remaining challenge in protein engineering is how to recombine beneficial substitutions. Systematic recombination studies show that poorly performing variants are usually obtained after recombination of 3 to 4 beneficial substitutions. This limits researchers in exploiting nature's potential in generating better enzymes. The Computer-assisted Recombination (CompassR) strategy provides a selection guide for beneficial substitutions that can be recombined to gradually improve enzyme performance by analysis of the relative free energy of folding (ΔΔGfold ). The performance of CompassR was evaluated by analysis of 84 recombinants located on 13 positions of Bacillus subtilis lipase A. The finally obtained variant F17S/V54K/D64N/D91E had a 2.7-fold improved specific activity in 18.3 % (v/v) 1-butyl-3-methylimidazolium chloride ([BMIM][Cl]). In essence, the deducted CompassR rule allows recombination of beneficial substitutions in an iterative manner and empowers researchers to generate better enzymes in a time-efficient manner.

Dietary glycerol monolaurate supplementation for the modification of functional properties of egg white protein.

BACKGROUND: Understanding the interactions between feed additives and the functional properties of egg white protein (EWP) may offer novel insights into the effects of feed additives on laying hens and may provide an alternative for modification of the functional properties of EWP by using laying hens as bioreactors. Glycerol monolaurate (GML) is widely used in the food industry as an effective antibacterial emulsifier. In this work, the effects of three doses of dietary GML supplementation (150, 300, and 450 mg kg-1 hen) on the functional properties of EWP were investigated. RESULTS: The hardness of EWP gels was significantly improved by 300 and 450 mg kg-1 GML supplementation. Foaming capacity (FC) and foaming stability (FS) were increased after GML treatment; 450 mg kg-1 GML supplementation showed the most significant improvements, with 44.82% in FC and 23.39% in FS. Stabilization of EWP-oil emulsions was also improved, supported by a slowed creaming process and the formation of smaller oil droplets. The heat denaturation temperature and rheological properties were also modified by dietary GML supplementation, implying improved thermal stability. CONCLUSION: Our study demonstrated that GML supplementation has the potential to modify the functional properties of EWP, broadening the application of GML and providing a new perspective for evaluation of the efficacy of feed additives. © 2019 Society of Chemical Industry.

Microbial diversity and chemical analysis of the starters used in traditional Chinese sweet rice wine.

Chinese sweet rice wine (CSRW) is a popular alcoholic drink in China. To investigate the effect of the microbial composition in CSRW starters on the final quality of the alcoholic drink, high-throughput sequencing on the fungal internal transcribed spacer II and bacterial 16S rRNA gene of the microflora in 8 starter samples was performed. The sequencing data analysis showed that 10 genera of yeasts and mold, and 11 genera of bacteria were identified. Fungal diversity analyses showed the significant variances in the fungal compositions among the starter samples. Starter microbiota were dominated by the Rhizopus genus in SZ5, LS6, NN8, QD9, DZ10 and DZ11, indicating its important role in starch hydrolysis during CSRW brewing. According to principal coordinate analyses, the bacterial composition had even less similarity among the 8 starter samples. The chemical determination of CSRW fermented with the 8 starters demonstrated that the CSRW quality and flavor were drastically influenced by the taxonomic composition and metabolism of the microbes in the starters. This study suggests it is necessary to standardize rice wine manufacturing and flavor classification by specifying starter and fermentation techniques.

[Medicinal laws and application examples of traditional Chinese medicine prescriptions for multiple aorto-arteritis].

To collect the literature on traditional Chinese medicine treatment for multiple aorto-arteritis from China National Knowledge Infrastructure(CNKI), establish prescriptions database after screening and normalizing the prescriptions reported in these literature, and analyze their medicinal rules by using traditional Chinese medicine inheritance support system. A total of 126 prescriptions for multiple aorto-arteritis were screened, containing 212 kinds of Chinese herbs. 26 core herb combinations were obtained by analysis of the commonly used herbs and their use frequencies. The treatment for multiple aorto-arteritis was manly of tonifying qi to nourish blood, promoting blood circulation to remove blood stasis, warming yang to dredge collaterals, and four new prescriptions were obtained. On this basis, two clinical cases were taken as the examples by analyzing the medicinal rules and the features of multiple aorto-arteritis. The first case showed that the herb combination of this study conformed to the basic core drug application mode and the core pathogenesis of multiple aorto-arteritis. The second case reflected the characteristics of the new prescriptions' herb combinations based on entropy hierarchical clustering. The practical analysis of the two clinical cases further indicated the reliability of the results. This study has certain guiding significance and reference value on new medicine research and development as well as clinical traditional Chinese medicine treatment for multiple aorto-arteritis.

Palmitoleic Acid Ameliorates Metabolic Disorders and Inflammation by Modulating Gut Microbiota and Serum Metabolites.

SCOPE: Palmitoleic acid (POA) is an omega-7 monounsaturated fatty acid that has been suggested to improve metabolic disorders. However, it remains unclear whether gut microbiota plays a role in the amelioration of metabolic disorders by POA. This study aims to investigate the regulation of POA on metabolism, as well as systemic inflammation in HFD-fed mice from the perspective of serum metabolome and gut microbiome. METHODS AND RESULTS: Thirty-six C57BL/6 male mice are randomly assigned to either a normal chow diet containing 1.9% w/w lard or an HFD containing 20.68% w/w lard or 20.68% w/w sea buckthorn pulp oil for 16 weeks. The study finds that POA significantly attenuated hyperlipidemia, insulin resistance, and inflammation in HFD-fed mice. POA supplementation significantly alters the composition of serum metabolites, particularly lipid metabolites in the glycerophospholipid metabolism pathway. POA obviously increases the abundance of Bifidobacterium and decreases the abundance of Allobaculum. Importantly, the study finds that glycerophosphocholine mediates the effect of Bifidobacterium on LDL-C, sphingomyelin mediates the effect of Bifidobacterium on IL-6, and maslinic acid mediates the effect of Allobaculum on IL-6. CONCLUSION: The results suggest that exogenous POA can improve metabolic disorders and inflammation in HFD-fed mice, potentially by modulating the serum metabolome and gut microbiome.

High-Fat Diet-Induced Decreased Circulating Bile Acids Contribute to Obesity Associated with Gut Microbiota in Mice.

The altered circulating bile acids (BAs) modulate gut microbiota, energy metabolism and various physiological functions. BA profiles in liver, serum, ileum and feces of HFD-fed mice were analyzed with normal chow diet (NCD)-fed mice after 16-week feeding. Furthermore, gut microbiota was analyzed and its correlation analysis with BA was performed. The result showed that long-term HFD feeding significantly decreased hepatic and serum BA levels, mainly attributed to the inhibition of hepatic BA synthesis and the reduced reabsorption efficiency of BAs in enterohepatic circulation. It also significantly impaired glucose and lipid homeostasis and gut microbiota in mice. We found significantly higher bile salt hydrolase activity in ileal microbes and a higher ratio of free BAs to conjugated BA content in ileal contents in HFD groups compared with NCD group mice, which might account for the activated intestinal farnesoid X receptor signaling on liver BA synthesis inhibition and reduced ileal reabsorption. The decreased circulating BAs were associated with the dysregulation of the lipid metabolism according to the decreased TGR5 signaling in the ileum and BAT. In addition, it is astonishing to find extremely high percentages of taurocholate and 12-OH BAs in liver and serum BA profiles of both groups, which was mainly attributed to the high substrate selectivity for 12-OH BAs of the intestinal BAs transporter during the ileal reabsorption of enterohepatic circulation. This study revealed a significant effect of long-term HFD feeding on the decreased circulating BA pool in mice, which impaired lipid homeostasis and gut microbiota, and collectively resulted in metabolic disorders and obesity.

Single-Cell Transcriptome Analysis Identified Core Genes and Transcription Factors in Mesenchymal Cell Differentiation during Liver Cirrhosis.

BACKGROUND: Mesenchymal cells, including hepatic stellate cells (HSCs), fibroblasts (FBs), myofibroblasts (MFBs), and vascular smooth muscle cells (VSMCs), are the main cells that affect liver fibrosis and play crucial roles in maintaining tissue homeostasis. The dynamic evolution of mesenchymal cells is very important but remains to be explored for researching the reversible mechanism of hepatic fibrosis and its evolution mechanism of hepatic fibrosis to cirrhosis. METHODS: Here, we analysed the transcriptomes of more than 50,000 human single cells from three cirrhotic and three healthy liver tissue samples and the mouse hepatic mesenchymal cells of two healthy and two fibrotic livers to reconstruct the evolutionary trajectory of hepatic mesenchymal cells from a healthy to a cirrhotic state, and a subsequent integrative analysis of bulk RNA sequencing (RNA-seq) data of HSCs from quiescent to active (using transforming growth factor ß1 (TGF-ß1) to stimulate LX-2) to inactive states. RESULTS: We identified core genes and transcription factors (TFs) involved in mesenchymal cell differentiation. In healthy human and mouse livers, the expression of NR1H4 and members of the ZEB families (ZEB1 and ZEB2) changed significantly with the differentiation of FB into HSC and VSMC. In cirrhotic human livers, VSMCs transformed into HSCs with downregulation of MYH11, ACTA2, and JUNB and upregulation of PDGFRB, RGS5, IGFBP5, CD36, A2M, SOX5, and MEF2C. Following HSCs differentiation into MFBs with the upregulation of COL1A1, TIMP1, and NR1H4, a small number of MFBs reverted to inactivated HSCs (iHSCs). The differentiation trajectory of mouse hepatic mesenchymal cells was similar to that in humans; however, the evolution trajectory and proportion of cell subpopulations that reverted from MFBs to iHSCs suggest that the mouse model may not accurately reflect disease progression and outcome in humans. CONCLUSIONS: Our analysis elucidates primary genes and TFs involved in mesenchymal cell differentiation during liver fibrosis using scRNA-seq data, and demonstrated the core genes and TFs in process of HSC activation to MFB and MFB reversal to iHSC using bulk RNA-seq data of human fibrosis induced by TGF-ß1. Furthermore, our findings suggest promising targets for the treatment of liver fibrosis and provide valuable insights into the molecular mechanisms underlying its onset and progression.

Discovery of Potent STT3A/B Inhibitors and Assessment of Their Multipathogen Antiviral Potential and Safety.

In the aftermath of the COVID-19 pandemic, opportunities to modulate biological pathways common to the lifecycles of viruses need to be carefully considered. N-linked glycosylation in humans is mediated exclusively by the oligosaccharyltransferase complex and is frequently hijacked by viruses to facilitate infection. As such, STT3A/B, the catalytic domain of the OST complex, became an intriguing drug target with broad-spectrum antiviral potential. However, due to the critical role N-linked glycosylation plays in a number of fundamental human processes, the toxicological ramifications of STT3A/B inhibition required attention commensurate to that given to antiviral efficacy. Herein, we describe how known STT3A/B inhibitor NGI-1 inspired the discovery of superior tool compounds which were evaluated in in vitro efficacy and translational safety (e.g., CNS, cardiovascular, liver) studies. The described learnings will appeal to those interested in the therapeutic utility of modulating N-linked glycosylation as well as the broader scientific community.

Dietary additive octyl and decyl glycerate modulates metabolism and inflammation under different dietary patterns with the contribution of the gut microbiota.

Octyl and decyl glycerate (ODG), a medium-chain triglyceride (MCT), is widely used as a food additive. Medium-chain monoglycerides, such as glycerol monolaurate and glycerol monocaprylate, were found to change the composition of the gut microbiota and influence glucose and lipid metabolism and inflammation. However, whether ODG influences the gut microbiota and whether the alteration in the gut microbiota contributes to the metabolic phenotype remain unknown. Under a normal-chow diet, mice were treated with or without different dosages of ODG (150, 800, 1600 mg kg-1) for 22 weeks. All doses of ODG significantly decreased the ratio of HDL to LDL cholesterol, improved the inflammation and insulin resistance, and increased the α-diversity of the gut microbiota and the abundance of Bifidobacterium and Turicibacter. Under a high-fat diet, mice were treated with or without 1600 mg kg-1 ODG for 16 weeks. The results demonstrated that ODG significantly alleviated the increase in the ratio of HDL to LDL cholesterol, insulin resistance, and inflammation caused by HFD. The expression of related genes was consistent with the above observations. ODG also altered the composition of the gut microbiota and increased the Bifidobacterium abundance under HFD. Our findings indicated that ODG similarly improved glucose metabolism and inflammation but exhibited differential effects on lipid metabolism under different dietary patterns. Furthermore, changes in the gut microbiota caused by ODG supplementation might contribute to the alteration in glucose and lipid metabolism and inflammation, which might be influenced by dietary patterns.

Food additive glycerol monocaprylate modulated systemic inflammation and gut microbiota without stimulating metabolic dysfunction in high-fat diet fed mice.

Recent findings imply that great consideration should be given to the potential health risks of food additives on gut microbiota. Glycerol monocaprylate (GMC) is a widely consumed food preservative and emulsifier. Our results indicated that GMC significantly ameliorated visceral fat accumulation and systemic inflammation in high-fat diet (HFD)-fed mice. Furthermore, GMC induced improvements on the composition and function of gut microbiota, resulting in increased beneficial gut bacteria (Bifidobacterium and Lactobacillus) and promoted production of short chain fatty acids. Notably, GMC-induced metabolic amelioration is closely related to the regulation in gut microbiota. Overall, our findings supported that unlike the emulsifiers previously reported to damage intestinal health, GMC performed the potential on attenuating HFD-induced metabolic disorders and gut microbiota dysbiosis, which also refined on the safety evaluation of GMC on gut microbiota. Our findings suggest that when evaluating the safety of food additives with regards to gut microbiota, it is important to take into account the specific characteristics of the additive in question, rather than simply relying on its classification.

Daily point-of-care ultrasound-assessment of central venous catheter-related thrombosis in critically ill patients: a prospective multicenter study.

PURPOSE: Central venous catheter (CVC)-related thrombosis (CRT) is a known complication in critically ill patients. However, its clinical significance remains unclear. The objective of the study was to evaluate the occurrence and evolution of CRT from CVC insertion to removal. METHODS: A prospective multicenter study was conducted in 28 intensive care units (ICUs). Duplex ultrasound was performed daily from CVC insertion until at least 3 days after CVC removal or before patient discharge from the ICU to detect CRT and to follow its progression. CRT diameter and length were measured and diameter > 7 mm was considered extensive. RESULTS: The study included 1262 patients. The incidence of CRT was 16.9% (95% confidence interval 14.8-18.9%). CRT was most commonly found in the internal jugular vein. The median time from CVC insertion to CRT onset was 4 (2-7) days, and 12% of CRTs occurred on the first day and 82% within 7 days of CVC insertion. CRT diameters > 5 mm and > 7 mm were found in 48% and 30% of thromboses. Over a 7-day follow-up, CRT diameter remained stable when the CVC was in place, whereas it gradually decreased after CVC removal. The ICU length of stay was longer in patients with CRT than in those without CRT, and the mortality was not different. CONCLUSION: CRT is a frequent complication. It can occur as soon as the CVC is placed and mostly during the first week following catheterization. Half of the thromboses are small but one-third are extensive. They are often non-progressive and may be resolved after CVC removal.

Dietary emulsifier glycerol monodecanoate affects the gut microbiota contributing to regulating lipid metabolism, insulin sensitivity and inflammation.

Glycerol monodecanoate (GMD) is a medium-chain monoacylglycerol that possesses emulsifying and antibacterial properties. The common emulsifiers carboxymethylcellulose and polysorbate-80 have been reported to cause intestinal microbiota dysbiosis and metabolic disturbances. Glycerol monolaurate (GML), another medium-chain monoacylglycerol, is often used as an emulsifier and could improve metabolism by regulating the gut microbiota. However, research on the effects of GMD on the metabolism and gut microbiota remains scarce. Mice were fed a normal chow diet with or without GMD (150, 800, and 1600 mg kg-1) for 22 weeks. Metabolism indicators and related genes, gut microbiota, and fecal SCFAs were analyzed. The results demonstrated that GMD significantly improved insulin sensitivity, reduced the serum LPS level, and decreased pro-inflammation cytokines including IL-1ß, tumor necrosis factor (TNF), and monocyte chemotactic protein 1 (MCP-1). Additionally, 150 and 1600 mg kg-1 GMD could significantly lower the blood glucose content. 1600 mg kg-1 GMD improved cholesterol metabolism and related gene expression compared to 150 and 800 mg kg-1 GMD. Moreover, 150 and 800 mg kg-1 GMD up-regulated the abundance of Lactobacillus and Turicibacter, while 1600 mg kg-1 GMD significantly up-regulated the abundance of Bifidobacterium. Our findings indicated that different doses of GMD had inconsistent effects on lipid metabolism by differentially altering the gut microbiota composition. Meanwhile, all doses of GMD showed excellent effects on increasing insulin sensitivity and improving inflammation.

Deoxynivalenol Degradation by Various Microbial Communities and Its Impacts on Different Bacterial Flora.

Deoxynivalenol, a mycotoxin that may present in almost all cereal products, can cause huge economic losses in the agriculture industry and seriously endanger food safety and human health. Microbial detoxifications using microbial consortia may provide a safe and effective strategy for DON mitigation. In order to study the interactions involving DON degradation and change in microbial flora, four samples from different natural niches, including a chicken stable (expJ), a sheep stable (expY), a wheat field (expT) and a horse stable (expM) were collected and reacted with purified DON. After being co-incubated at 30 °C with 130 rpm shaking for 96 h, DON was reduced by 74.5%, 43.0%, 46.7%, and 86.0% by expJ, expY, expT, and expM, respectively. After DON (0.8 mL of 100 µg/mL) was co-cultivated with 0.2 mL of the supernatant of each sample (i.e., suspensions of microbial communities) at 30 °C for 96 h, DON was reduced by 98.9%, 99.8%, 79.5%, and 78.9% in expJ, expY, expT, and expM, respectively, and was completely degraded after 8 days by all samples except of expM. DON was confirmed being transformed into de-epoxy DON (DOM-1) by the microbial community of expM. The bacterial flora of the samples was compared through 16S rDNA flux sequencing pre- and post the addition of DON. The results indicated that the diversities of bacterial flora were affected by DON. After DON treatment, the most abundant bacteria belong to Galbibacter (16.1%) and Pedobacter (8.2%) in expJ; Flavobacterium (5.9%) and Pedobacter (5.5%) in expY; f_Microscillaceae (13.5%), B1-7BS (13.4%), and RB41 (10.5%) in expT; and Acinetobacter (24.1%), Massilia (8.8%), and Arthrobacter (7.6%) in expM. This first study on the interactions between DON and natural microbial flora provides useful information and a methodology for further development of microbial consortia for mycotoxin detoxifications.

Consumption of Wheat Peptides Improves Functional Constipation: A Translational Study in Humans and Mice.

SCOPE: Wheat peptides (WP) are rich in glutamic acid, glutamine, and other bioactive compounds that may benefit gut function and health. This study aims to evaluate the effects of regular consumption of WP on constipation-induced complications and gut microbiota in humans and mice. METHODS AND RESULTS: A randomized trial of 49 functional constipation participants is conducted. The weekly amount of spontaneous bowel movements (SBM) increases by 2.09 per week after WP treatment, and by 0.40 per week among the placebo group (PL). Concomitantly, the secondary outcomes show significant improvements in the quality of life-related to constipation (PAC-QOL), constipation severity, and satisfaction with the intervention. In the animal study, WP effectively alleviates constipation symptoms and affects the secretion of intestinal mobility-related neurotransmitters and gastrointestinal hormones in loperamide-induced constipation mice. Additionally, WP regulates the gene and protein expression levels of water-electrolyte metabolism and intestinal mobility. Furthermore, WP treatment decreases the abundance of several gut microbiota positively correlated to constipation (Turicibacter, Bacteroides_f_Bacteroidaceae, and Streptococcus) in mice. CONCLUSION: WP ameliorates constipation in humans and mice, which could be partly explained by improving water-electrolyte metabolism, boosting intestinal motility, and reshaping gut microbiota.