Genetic and structural basis of the human anti-α-galactosyl antibody response.

Humans lack the capacity to produce the Galα1-3Galß1-4GlcNAc (α-gal) glycan, and produce anti-α-gal antibodies upon exposure to the carbohydrate on a diverse set of immunogens, including commensal gut bacteria, malaria parasites, cetuximab, and tick proteins. Here we use X-ray crystallographic analysis of antibodies from α-gal knockout mice and humans in complex with the glycan to reveal a common binding motif, centered on a germline-encoded tryptophan residue at Kabat position 33 (W33) of the complementarity-determining region of the variable heavy chain (CDRH1). Immunoglobulin sequencing of anti-α-gal B cells in healthy humans and tick-induced mammalian meat anaphylaxis patients revealed preferential use of heavy chain germline IGHV3-7, encoding W33, among an otherwise highly polyclonal antibody response. Antigen binding was critically dependent on the presence of the germline-encoded W33 residue for all of the analyzed antibodies; moreover, introduction of the W33 motif into naive IGHV3-23 antibody phage libraries enabled the rapid selection of α-gal binders. Our results outline structural and genetic factors that shape the human anti-α-galactosyl antibody response, and provide a framework for future therapeutics development.

Opportunities to produce food from substantially less land.

The vast majority of the food we eat comes from land-based agriculture, but recent technological advances in agriculture and food technology offer the prospect of producing food using substantially less or even virtually no land. For example, indoor vertical farming can achieve very high yields of certain crops with a very small area footprint, and some foods can be synthesized from inorganic precursors in industrial facilities. Animal-based foods require substantial land per unit of protein or per calorie and switching to alternatives could reduce demand for some types of agricultural land. Plant-based meat substitutes and those produced through fermentation are widely available and becoming more sophisticated while in the future cellular agricultural may become technically and economical viable at scale. We review the state of play of these potentially disruptive technologies and explore how they may interact with other factors, both endogenous and exogenous to the food system, to affect future demand for land.

Transcriptomic analysis of the longissimus thoracis muscle in pigs has identified molecular regulatory patterns associated with meat quality.

Meat quality is a critical aspect of pig breeding. In addition to genetics, meat quality is also influenced by nutritional and environmental factors. In this study, three pig breeds, Shengxianhua, Jiaxing, and Qinglian Black (SXH, JXB and QLB), were used as experimental animals. Transcriptional analysis was performed on the longissimus thoracis (LT) muscle to investigate variations in intramuscular fat (IMF), inosine monophosphate (IMP), amino acids, and muscle fiber morphology across different breeds. Ingenuity canonical pathway analysis (IPA) identified biological processes and key driver genes related to metabolism and muscle development. Additionally, weighted gene co-expression network analysis (WGCNA) revealed gene modules associated with IMP. KEGG and GO analyses identified specific biological processes and signaling pathways related to IMP, including the Oxidative Phosphorylation pathway and rRNA Metabolic Processes. These findings provide novel insights into the molecular regulatory mechanisms underlying meat quality variations among pig breeds.

Transcriptomic analysis of different intramuscular fat contents on the flavor of the longissimus dorsi tissues from Guangling donkey.

BACKGROUND: In this study, researchers aimed to explore the impact of intramuscular fat (IMF) concentration on the flavor of donkey meat, specifically in the longissimus dorsi muscle of Guangling donkeys. The internal volatile organic compounds that cause the flavor differences between donkey muscles are not clear at present. Transcriptomic technologies were utilized to analyze gene expression and its relationship to donkey meat flavor. METHOD: Thirty Guangling donkeys had their IMF content evaluated in the longissimus dorsi muscle. Based on IMF content, 16 donkeys of similar ages were divided into two groups: low-fat (L) and high-fat (H). Headspace solid-phase microextraction Gas chromatography-mass spectrometry (HS-SPME-GC-MS) and headspace solid phase microextraction mass spectrometry were used to identify potential flavor components that differed between the two groups. RESULTS: Five key volatile substances were identified, and WGCNA and KEGG analysis was conducted to analyze the genes associated with these substances. The results showed that pathways like PPAR signaling, nucleotide excision repair, glucagon signaling, arachidonic acid metabolism, and glycolysis/glycogenesis were involved in lipid deposition. Additionally, a gene-gene interaction network map was constructed, highlighting the importance of hub genes such as EEF2, DDX49, GAP43, SNAP25, NDUFS8, MRPS11, RNASEH2A, POLR2E, POLR2C and ALB in regulating key flavor substances. CONCLUSION: This study provided valuable insights into the regulation of genes and protein expression related to flavor substances in donkey meat. It also deepened understanding of the influence of IMF on flavor and laid a foundation for future molecular breeding improvements in Guangling donkeys.

IgE and anaphylaxis specific to the carbohydrate alpha-gal depend on IL-4.

BACKGROUND: Alpha-gal (Galα1-3Galß1-4GlcNAc) is a carbohydrate with the potential to elicit fatal allergic reactions to mammalian meat and drugs of mammalian origin. This type of allergy is induced by tick bites, and therapeutic options for this skin-driven food allergy are limited to the avoidance of the allergen and treatment of symptoms. Thus, a better understanding of the immune mechanisms resulting in sensitization through the skin is crucial, especially in the case of a carbohydrate allergen for which underlying immune responses are poorly understood. OBJECTIVE: We aimed to establish a mouse model of alpha-gal allergy for in-depth immunologic analyses. METHODS: Alpha-galactosyltransferase 1-deficient mice devoid of alpha-gal glycosylations were sensitized with the alpha-gal-carrying self-protein mouse serum albumin by repetitive intracutaneous injections in combination with the adjuvant aluminum hydroxide. The role of basophils and IL-4 in sensitization was investigated by antibody-mediated depletion. RESULTS: Alpha-gal-sensitized mice displayed increased levels of alpha-gal-specific IgE and IgG1 and developed systemic anaphylaxis on challenge with both alpha-gal-containing glycoproteins and glycolipids. In accordance with alpha-gal-allergic patients, we detected elevated numbers of basophils at the site of sensitization as well as increased numbers of alpha-gal-specific B cells, germinal center B cells, and B cells of IgE and IgG1 isotypes in skin-draining lymph nodes. By depleting IL-4 during sensitization, we demonstrated for the first time that sensitization and elicitation of allergy to alpha-gal and correspondingly to a carbohydrate allergen is dependent on IL-4. CONCLUSION: These findings establish IL-4 as a potential target to interfere with alpha-gal allergy elicited by tick bites.

RNA sequencing identifies key genes involved in intramuscular fat deposition in chickens at different developmental stages.

BACKGROUND: Intramuscular fat (IMF) is an important factor in meat quality, and triglyceride (TG) and Phospholipids (PLIP), as the main components of IMF, are of great significance to the improvement of meat quality. RESULTS: In this study, we used 30 RNA sequences generated from the transcriptome of chicken breast muscle tissues at different developmental stages to construct a gene expression matrix to map RNA sequence reads to the chicken genome and identify the transcript of origin. We used weighted gene co-expression network analysis (WGCNA) and identified 27 co-expression modules, 10 of which were related to TG and PLIP. We identified 150 highly-connected hub genes related to TG and PLIP, respectively, which were found to be mainly enriched in the adipocytokine signaling pathway, MAPK signaling pathway, mTOR signaling pathway, FoxO signaling pathway, and TGF-beta signaling pathway. Additionally, using the BioMart database, we identified 134 and 145 candidate genes related to fat development in the TG-related module and PLIP-related module, respectively. Among them, RPS6KB1, BRCA1, CDK1, RPS3, PPARGC1A, ACSL1, NDUFAB1, NDUFA9, ATP5B and PRKAG2 were identified as candidate genes related to fat development and highly-connected hub genes in the module, suggesting that these ten genes may be important candidate genes affecting IMF deposition. CONCLUSIONS: RPS6KB1, BRCA1, CDK1, RPS3, PPARGC1A, ACSL1, NDUFAB1, NDUFA9, ATP5B and PRKAG2 may be important candidate genes affecting IMF deposition. The purpose of this study was to identify the co-expressed gene modules related to chicken IMF deposition using WGCNA and determine key genes related to IMF deposition, so as to lay a foundation for further research on the molecular regulation mechanism underlying chicken fat deposition.

Transcriptomic analysis reveals differentially expressed genes associated with meat quality in Chinese Dagu chicken and AA+ broiler roosters.

BACKGROUND: With the improvement of living standards, the quality of chicken has become a significant concern. Chinese Dagu Chicken (dual-purpose type) and Arbor Acres plus broiler (AA+ broiler) (meat-type) were selected as the research subjects in this study, the meat quality of the breast and leg muscles were measured. However, the molecular mechanism(s) underlying regulation of muscle development are not yet fully elucidated. Therefore, finding molecular markers or major genes that regulate muscle quality has become a crucial breakthrough in chicken breeding. Unraveling the molecular mechanism behind meat traits in chicken and other domestic fowl is facilitated by identifying the key genes associated with these developmental events. Here, a comparative transcriptomic analysis of chicken meat was conducted on breast muscles (BM) and leg muscles (LM) in AA+ broilers (AA) and Dagu chicken (DG) to explore the differences in their meat traits employing RNA-seq. RESULTS: Twelve cDNA libraries of BM and LM from AA and DG were constructed from four experimental groups, yielding 14,464 genes. Among them, Dagu chicken breast muscles (DGB) vs AA+ broilers breast muscles (AAB) showed 415 upregulated genes and 449 downregulated genes, Dagu chicken leg muscles (DGL) vs AA+ broilers leg muscles (AAL) exhibited 237 upregulated genes and 278 downregulated genes, DGL vs DGB demonstrated 391 upregulated genes and 594 downregulated genes, and AAL vs AAB displayed 122 upregulated genes and 154 downregulated genes. 13 genes, including nine upregulated genes (COX5A, COX7C, NDUFV1, UQCRFS1, UQCR11, BRT-1, FGF14, TMOD1, MYOZ2) and four downregulated genes (MYBPC3, MYO7B, MTMR7, and TNNC1), were found to be associated with the oxidative phosphorylation signaling pathway. Further analysis revealed that the differentially expressed genes (DEGs) from muscle were enriched in various pathways, such as metabolic pathways, oxidative phosphorylation, carbon metabolism, glycolysis, extracellular matrix-receptor interaction, biosynthesis of amino acids, focal adhesion, vascular smooth muscle contraction, and cardiac muscle contraction, all of which are involved in muscle development and metabolism. This study also measured the meat quality of the breast and leg muscles from the two breeds, which demonstrated superior overall meat quality in Chinese Dagu Chicken compared to the AA+ broiler. CONCLUSIONS: Our findings show that the meat quality of dual-purpose breeds (Chinese Dagu chicken) is higher than meat-type (AA+ broiler), which may be related to the DEGs regulating muscle development and metabolism. Our findings also provide transcriptomic insights for a comparative analysis of molecular mechanisms underlying muscle development between the two breeds, and have practical implications for the improvement of chicken breeding practices.

Transcriptomic and metabolomic dissection of skeletal muscle of crossbred Chongming white goats with different meat production performance.

BACKGROUND: The transcriptome and metabolome dissection of the skeletal muscle of high- and low- growing individuals from a crossbred population of the indigenous Chongming white goat and the Boer goat were performed to discover the potential functional differentially expressed genes (DEGs) and differential expression metabolites (DEMs). RESULTS: A total of 2812 DEGs were detected in 6 groups at three time stages (3,6,12 Month) in skeletal muscle using the RNA-seq method. A DEGs set containing seven muscle function related genes (TNNT1, TNNC1, TNNI1, MYBPC2, MYL2, MHY7, and CSRP3) was discovered, and their expression tended to increase as goat muscle development progressed. Seven DEGs (TNNT1, FABP3, TPM3, DES, PPP1R27, RCAN1, LMOD2) in the skeletal muscle of goats in the fast-growing and slow-growing groups was verified their expression difference by reverse transcription-quantitative polymerase chain reaction. Further, through the Liquid chromatography-mass spectrometry (LC-MS) approach, a total of 183 DEMs in various groups of the muscle samples and these DEMs such as Queuine and Keto-PGF1α, which demonstrated different abundance between the goat fast-growing group and slow-growing group. Through weighted correlation network analysis (WGCNA), the study correlated the DEGs with the DEMs and identified 4 DEGs modules associated with 18 metabolites. CONCLUSION: This study benefits to dissection candidate genes and regulatory networks related to goat meat production performance, and the joint analysis of transcriptomic and metabolomic data provided insights into the study of goat muscle development.

Genomic exploration of the fermented meat isolate Staphylococcus shinii IMDO-S216 with a focus on competitiveness-enhancing secondary metabolites.

BACKGROUND: Staphylococcus shinii appears as an umbrella species encompassing several strains of Staphylococcus pseudoxylosus and Staphylococcus xylosus. Given its phylogenetic closeness to S. xylosus, S. shinii can be found in similar ecological niches, including the microbiota of fermented meats where the species may contribute to colour and flavour development. In addition to these conventional functionalities, a biopreservation potential based on the production of antagonistic compounds may be available. Such potential, however, remains largely unexplored in contrast to the large body of research that is available on the biopreservative properties of lactic acid bacteria. The present study outlines the exploration of the genetic basis of competitiveness and antimicrobial activity of a fermented meat isolate, S. shinii IMDO-S216. To this end, its genome was sequenced, de novo assembled, and annotated. RESULTS: The genome contained a single circular chromosome and eight plasmid replicons. Focus of the genomic exploration was on secondary metabolite biosynthetic gene clusters coding for ribosomally synthesized and posttranslationally modified peptides. One complete cluster was coding for a bacteriocin, namely lactococcin 972; the genes coding for the pre-bacteriocin, the ATP-binding cassette transporter, and the immunity protein were also identified. Five other complete clusters were identified, possibly functioning as competitiveness factors. These clusters were found to be involved in various responses such as membrane fluidity, iron intake from the medium, a quorum sensing system, and decreased sensitivity to antimicrobial peptides and competing microorganisms. The presence of these clusters was equally studied among a selection of multiple Staphylococcus species to assess their prevalence in closely-related organisms. CONCLUSIONS: Such factors possibly translate in an improved adaptation and competitiveness of S. shinii IMDO-S216 which are, in turn, likely to improve its fitness in a fermented meat matrix.

Integrated analysis strategy of genome-wide functional gene mining reveals DKK2 gene underlying meat quality in Shaziling synthesized pigs.

BACKGROUND: Shaziling pig is a well-known indigenous breed in China who has superior meat quality traits. However, the genetic mechanism and genomic evidence underlying meat quality characteristics of Shaziling pigs are still unclear. To explore and investigate the germplasm characteristics of Shaziling pigs, we totally analyzed 67 individual's whole genome sequencing data for the first time (20 Shaziling pigs [S], 20 Dabasha pigs [DBS], 11 Yorkshire pigs [Y], 10 Berkshire pigs [BKX], 5 Basha pigs [BS] and 1 Warthog). RESULTS: A total of 2,538,577 SNPs with high quality were detected and 9 candidate genes which was specifically selected in S and shared in S to DBS were precisely mined and screened using an integrated analysis strategy of identity-by-descent (IBD) and selective sweep. Of them, dickkopf WNT signaling pathway inhibitor 2 (DKK2), the antagonist of Wnt signaling pathway, was the most promising candidate gene which was not only identified an association of palmitic acid and palmitoleic acid quantitative trait locus in PigQTLdb, but also specifically selected in S compared to other 48 Chinese local pigs of 12 populations and 39 foreign pigs of 4 populations. Subsequently, a mutation at 12,726-bp of DKK2 intron 1 (g.114874954 A > C) was identified associated with intramuscular fat content using method of PCR-RFLP in 21 different pig populations. We observed DKK2 specifically expressed in adipose tissues. Overexpression of DKK2 decreased the content of triglyceride, fatty acid synthase and expression of relevant genes of adipogenic and Wnt signaling pathway, while interference of DKK2 got contrary effect during adipogenesis differentiation of porcine preadipocytes and 3T3-L1 cells. CONCLUSIONS: Our findings provide an analysis strategy for mining functional genes of important economic traits and provide fundamental data and molecular evidence for improving pig meat quality traits and molecular breeding.

Identification and characterization of structural variants related to meat quality in pigs using chromosome-level genome assemblies.

BACKGROUND: Many studies have been performed to identify various genomic loci and genes associated with the meat quality in pigs. However, the full genetic architecture of the trait still remains unclear in part because of the lack of accurate identification of related structural variations (SVs) which resulted from the shortage of target breeds, the limitations of sequencing data, and the incompleteness of genome assemblies. The recent generation of a new pig breed with superior meat quality, called Nanchukmacdon, and its chromosome-level genome assembly (the NCMD assembly) has provided new opportunities. RESULTS: By applying assembly-based SV calling approaches to various genome assemblies of pigs including Nanchukmacdon, the impact of SVs on meat quality was investigated. Especially, by checking the commonality of SVs with other pig breeds, a total of 13,819 Nanchukmacdon-specific SVs (NSVs) were identified, which have a potential effect on the unique meat quality of Nanchukmacdon. The regulatory potentials of NSVs for the expression of nearby genes were further examined using transcriptome- and epigenome-based analyses in different tissues. CONCLUSIONS: Whole-genome comparisons based on chromosome-level genome assemblies have led to the discovery of SVs affecting meat quality in pigs, and their regulatory potentials were analyzed. The identified NSVs will provide new insights regarding genetic architectures underlying the meat quality in pigs. Finally, this study confirms the utility of chromosome-level genome assemblies and multi-omics analysis to enhance the understanding of unique phenotypes.

A historical cohort study with 27,754 individuals on the association between meat consumption and gastrointestinal tract and colorectal cancer incidence.

In order to explore the association between meat consumption and gastrointestinal/colorectal cancer (CRC) risk and to estimate the Israeli population attributable fraction (PAF), we conducted a collaborative historical cohort study using the individual participant data of seven nutritional studies from the past 6 decades. We included healthy adult men and women who underwent a nutritional interview. Dietary assessment data, using food-frequency or 24-h recall questionnaires, were harmonized. The study file was linked to the National Cancer and death registries. Among 27,754 participants, 1216 (4.4%) were diagnosed with gastrointestinal cancers and 839 (3.0%) with CRC by the end of 2016. Using meta-analysis methods applied to Cox proportional hazard models (adjusted for daily energy intake, sex, age, ethnic origin, education and smoking),100 g/day increments in beef, red meat and poultry consumption, and 50 g/day increment in processed meat consumption were associated with hazard ratios (HRs) and 95% confidence intervals of 1.46 (1.06-2.02), 1.15 (0.87-1.52), 1.06 (0.89-1.26), and 0.93 (0.76-1.12), respectively, for CRC. Similar results were obtained for gastrointestinal cancer, although red meat consumption reached statistical significance (HR = 1.27; 95%CI: 1.02-1.58). The PAFs associated with a reduction to a maximum of 50 g/day in the consumption of red meat were 2.7% (95%CI: -1.9 to 12.0) and 5.2% (0.3-13.9) for CRC and gastrointestinal cancers, respectively. Reduction of beef consumption to a maximum of 50 g/day will result in a CRC PAF reduction of 7.5% (0.7%-24.3%). While beef consumption was associated with gastrointestinal/CRC excess risk, poultry consumption was not. A substantial part of processed meat consumption in Israel is processed poultry, perhaps explaining the lack of association with CRC.

Clinical Presentation and Outcomes of Alpha-Gal Syndrome.

BACKGROUND AND AIMS: Alpha-gal syndrome (AGS) is an IgE-mediated allergic reaction to galactose-α-1,3-galactose, primarily linked with Lone Star tick bites in the United States. It presents with symptoms ranging from urticaria and gastrointestinal (GI) manifestations to delayed anaphylaxis following red meat consumption. We aimed to study AGS patients' clinical manifestations, diagnosis, and outcomes. METHODS: A retrospective chart review of patients who underwent serological testing for suspected AGS between 2014 and 2023 at Mayo Clinic was performed. Patients with positive serology were age and sex matched with those who tested negative. Clinical characteristics of seropositive cohort with and without GI symptoms were compared, and outcomes assessed. RESULTS: Of 1260 patients who underwent testing, 124 tested positive for AGS. They were matched with 380 seronegative control subjects. AGS patients reported a higher frequency of tick bites (odds ratio [OR], 26.0; 95% confidence interval [CI], 9.8-68.3), reported a higher prevalence of urticaria (56% vs 37%; P = .0008), and were less likely to have asthma (OR, 0.4; 95% CI, 0.3-0.7). They had a lower prevalence of heartburn (6% vs 12%; P = .03) and bloating (6% vs 13%; P = .03). A total of 47% had GI symptoms, and a higher proportion were female than those without GI symptoms (69% vs 35%; P = .002). During a mean follow-up of 27 months, 22 of 40 patients reported symptom resolution after avoiding red meat, and 7 were able to transition to regular diet. CONCLUSIONS: A diagnosis of AGS should be strongly considered in patients with a history of tick bites and clinical presentation of allergic or GI manifestations. Dietary intervention is effective in most but not all patients.

Development of a novel Japanese eel myoblast cell line for application in cultured meat production.

The present study investigates the isolation, analysis, and characterization of primary cultured cells derived from the muscle tissue of Japanese eel (Anguilla japonica), culminating in establishing a spontaneously immortalized myoblast cell line, JEM1129. We isolated satellite cells from eel muscle tissue to establish a foundation for cultured eel meat production. While initial cell cultures contained myoblasts, continued passaging led to a decline in myoblast characteristics and an increase in fibroblast-like cells. RNA-Seq and RT-qPCR analyses showed significant downregulation of well-established markers for satellite cells and myoblasts, such as pax7a and myoD, over successive passages, highlighting a loss of myoblastic traits. Single-cell cloning was employed to overcome this challenge and maintain myoblast purity, leading to the successful creation of the JEM1129 cell line. These JEM1129 cells demonstrated enhanced expression of myoblast marker genes, exceeding the initial primary culture cell population. The cells showed strong myotube formation, particularly when cultured in a differentiation medium, indicating their robust potential for muscle development. The JEM1129 cell line represents a significant advancement in the cultivation of eel muscle cells, offering a promising avenue for cultured meat production. The findings contribute to a deeper understanding of muscle cell biology and provide valuable insights into using fish-derived myoblasts for cultured meat production.

Meat and meat products as potential sources of emerging MDR Bacillus cereus: groEL gene sequencing, toxigenic and antimicrobial resistance.

BACKGROUND: Bacillus cereus is implicated in severe foodborne infection in humans. This study intended to assess the occurrence, groEL gene sequencing, biofilm production, and resistance profiles of emerged multidrug resistant (MDR) B. cereus in meat and meat product samples. Moreover, this work highlights the virulence and toxigenic genes (hblABCD complex, nheABC complex, cytK, ces, and pc-plc) and antimicrobial resistance genes (bla1, tetA, bla2, tetB, and ermA). METHODS: Consequently, 200 samples (sausage, minced meat, luncheon, beef meat, and liver; n = 40 for each) were indiscriminately collected from commercial supermarkets in Port Said Province, Egypt, from March to May 2021. Subsequently, food samples were bacteriologically examined. The obtained isolates were tested for groEL gene sequence analysis, antibiotic susceptibility, biofilm production, and PCR screening of toxigenic and resistance genes. RESULTS: The overall prevalence of B. cereus among the inspected food samples was 21%, where the highest predominance was detected in minced meat (42.5%), followed by beef meat (30%). The phylogenetic analysis of the groEL gene exposed that the examined B. cereus strain disclosed a notable genetic identity with other strains from the USA and China. Moreover, the obtained B. cereus strains revealed ß-hemolytic activity, and 88.1% of the recovered strains tested positive for biofilm production. PCR evidenced that the obtained B. cereus strains usually inherited the nhe complex genes (nheA and nheC: 100%, and nheB: 83.3%), followed by cytK (76.2%), hbl complex (hblC and hblD: 59.5%, hblB: 16.6%, and hblA: 11.9%), ces (54.7%), and pc-plc (30.9%) virulence genes. Likewise, 42.9% of the examined B. cereus strains were MDR to six antimicrobial classes and encoded bla1, bla2, ermA, and tetA genes. CONCLUSION: In summary, this study highlights the presence of MDR B. cereus in meat and meat products, posing a significant public health risk. The contamination by B. cereus is common in minced meat and beef meat. The molecular assay is a reliable fundamental tool for screening emerging MDR B. cereus strains in meat and meat products.

Tick bites, IgE to galactose-alpha-1,3-galactose and urticarial or anaphylactic reactions to mammalian meat: The alpha-gal syndrome.

The recent recognition of a syndrome of tick-acquired mammalian meat allergy has transformed the previously held view that mammalian meat is an uncommon allergen. The syndrome, mediated by IgE antibodies against the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal), can also involve reactions to visceral organs, dairy, gelatin and other products, including medications sourced from non-primate mammals. Thus, fittingly, this allergic disorder is now called the alpha-gal syndrome (AGS). The syndrome is strikingly regional, reflecting the important role of tick bites in sensitization, and is more common in demographic groups at risk of tick exposure. Reactions in AGS are delayed, often by 2-6 h after ingestion of mammalian meat. In addition to classic allergic symptomatology such as urticaria and anaphylaxis, AGS is increasingly recognized as a cause of isolated gastrointestinal morbidity and alpha-gal sensitization has also been linked with cardiovascular disease. The unusual link with tick bites may be explained by the fact that allergic cells and mediators are mobilized to the site of tick bites and play a role in resistance against ticks and tick-borne infections. IgE directed to alpha-gal is likely an incidental consequence of what is otherwise an adaptive immune strategy for host defense against endo- and ectoparasites, including ticks.

Increasing prevalence of galactose-α-1,3-galactose sensitization in the Danish general adult population.

BACKGROUND: Alpha-gal syndrome is a novel food allergy to the oligosaccharide galactose-α-1,3-galactose (alpha-gal) present in mammalian meat. Tick bites are considered an important route of sensitization to alpha-gal. Data on alpha-gal sensitization in the general population is scant. We utilized a unique data source of repeated population-based health examination studies to assess prevalence, time trends, risk factors, and characteristics of alpha-gal sensitization. METHODS: Alpha-gal sensitization was assessed in >11.000 adults from four health examination studies of randomly invited residents in the Copenhagen region conducted in 1990-1991, 2011-2012, 2012-2015, and 2016-2017. Alpha-gal sensitization was defined as serum specific IgE (sIgE) to alpha-gal ≥0.1 kUA/L; ≥0.35 kUA/L; ≥0.7 kUA/L; ≥3.5 kUA/L. The population was characterized according to genetically determined ABO blood group, aeroallergen sensitization, and pets at home. RESULTS: The prevalence of sIgE to alpha-gal ≥0.1 kUA/L was 1.3% in 1990-1991, 3.7% in 2012-2015 and 3.2% in 2016-2017. Of those sensitized to alpha-gal >97% reported to consume red meat at least once a week, even for sIgE to alpha-gal ≥3.5 kUA/L. Male sex, older age, aeroallergen sensitization, cat at home, and blood group A were associated with increased odds of alpha-gal sensitization. The known protective effect of blood group B was confirmed. CONCLUSION: In this general adult population, the prevalence of alpha-gal sensitization had doubled from 1990-1991 to 2016-2017. This could potentially be due to increased tick exposure and an increased atopic predisposition.

Red Meat Intake and the Risk of Cardiovascular Diseases: A Prospective Cohort Study in the Million Veteran Program.

BACKGROUND: Red meat consumption was associated with an increased risk of cardiovascular disease (CVD) in prospective cohort studies and a profile of biomarkers favoring high CVD risk in short-term controlled trials. However, several recent systematic reviews and meta-analyses concluded with no or weak evidence for limiting red meat intake. OBJECTIVES: To prospectively examine the associations between red meat intake and incident CVD in an ongoing cohort study with diverse socioeconomic and racial or ethnic backgrounds. METHODS: Our study included 148,506 participants [17,804 female (12.0%)] who were free of cancer, diabetes, and CVD at baseline from the Million Veteran Program. A food frequency questionnaire measured red meat intakes at baseline. Nonfatal myocardial infarction and acute ischemic stroke were identified through a high-throughput phenotyping algorithm, and fatal CVD events were identified by searching the National Death Index. RESULTS: Comparing the extreme categories of intake, the multivariate-adjusted relative risks of CVD was 1.18 (95% CI: 1.01, 1.38; P-trend < 0.0001) for total red meat, 1.14 (95% CI: 0.96, 1.36; P-trend = 0.01) for unprocessed red meat, and 1.29 (95% CI: 1.04, 1.60; P-trend = 0.003) for processed red meat. We observed a more pronounced positive association between red meat intake and CVD in African American participants than in White participants (P-interaction = 0.01). Replacing 0.5 servings/d of red meat with 0.5 servings/d of nuts, whole grains, and skimmed milk was associated with 14% (RR: 0.86; 95% CI: 0.83, 0.90), 7% (RR: 0.93; 95% CI: 0.89, 0.96), and 4% (RR: 0.96; 95% CI: 0.94, 0.99) lower risks of CVD, respectively. CONCLUSIONS: Red meat consumption is associated with an increased risk of CVD. Our findings support lowering red meat intake and replacing red meat with plant-based protein sources or low-fat dairy foods as a key dietary recommendation for the prevention of CVD.

The Effect of Adding Protein to a Carbohydrate Meal on Postprandial Glucose and Insulin Responses: A Systematic Review and Meta-Analysis of Acute Controlled Feeding Trials.

BACKGROUND: Protein influences acute postprandial glucose and insulin responses, but the effects of dose, protein type, and health status are unknown. OBJECTIVES: We aimed to determine the acute effect of adding protein to carbohydrate on postprandial responses and identify effect modifiers. METHODS: We searched MEDLINE, EMBASE, and Cochrane databases through 30 July, 2023 for acute, crossover trials comparing acute postprandial responses elicited by carbohydrate-containing test meals with and without added protein in adults without diabetes or with type 2 (T2DM) or type 1 (T1DM) diabetes mellitus. Group data were pooled separately using generic inverse variance with random-effects models and expressed as the ratio of means with 95% confidence interval. Risk of bias and certainty of evidence (Grading of Recommendations Assessment, Development, and Evaluation) were assessed. RESULTS: In 154 trial comparisons of animal, dairy, and plant proteins (without diabetes, n = 22, 67, 32, respectively; T2DM, n = 14, 16, 3, respectively), each gram protein per gram available carbohydrate (g/g) reduced the glucose area under the curve (AUC) less in adults with T2DM than in those without diabetes (-10% compared with -50%, P < 0.05) but increased the insulin AUC similarly (+76% compared with +56%). In subjects without diabetes, each g/g of dairy and plant protein reduced glucose AUC by 52% and 55%, respectively, and increased the insulin AUC by 64% and 45%, respectively (all P < 0.05). Animal proteins significantly reduced the glucose AUC by 31% and increased the insulin AUC by 37% (pooled effects) but without a significant dose-response. In adults with T2DM, animal protein reduced the glucose AUC by 13% and increased the insulin AUC by 105%, with no significant dose-response. Dairy protein reduced the glucose AUC by 18% (no dose-response), but each g/g increased the insulin AUC by 34% (P < 0.05). In adults with T1DM, protein increased the glucose AUC by 40% (P < 0.05, n = 5). Data source (reported AUC compared with calculated AUC) and study methodology quality significantly modified some outcomes and contributed to high between-study heterogeneity. CONCLUSIONS: In people without diabetes, adding dairy or plant protein to a carbohydrate-containing meal elicits physiologically significant reductions in glucose AUC and increases insulin AUC. Animal protein may slightly reduce the glucose AUC and may increase the insulin AUC. In people with T2DM, protein may not have such large and consistent effects. Further research is needed to determine if the effects of protein differ by health status and protein source. This study was registered at PROSPERO as CRD42022322090.

Higher Expression of miR-15b-5p with Inclusion of Fresh, Lean Beef as Part of a Healthy Dietary Pattern Is Inversely Associated with Markers of Cardiometabolic Disease Risk.

BACKGROUND: Considerable controversy exists surrounding the consumption of red meat and its impacts on cardiometabolic health and if it may further impact risk factors at the molecular level. OBJECTIVE: The purpose of this study was to examine the acute effects of dietary patterns, varying in red meat quantity, on the expression of circulating microRNAs (miRNAs), which are emerging biomarkers of metabolic dysfunction and chronic disease severity. METHODS: Secondary analyses were performed on plasma samples collected within a randomized, crossover design study in 16 women with overweight (mean ± standard deviation, age = 33 ± 9.89 y; body mass index = 27.9 ± 1.66 kg/m2). Participants were provided with eucaloric, isonitrogenous diets (15% of daily intake as protein) containing either 2 servings of fresh, lean beef/day (BEEF) or 0 servings of fresh, lean beef/day (PLANT) for 7 d/pattern. Fasting blood samples were collected at the end of each dietary pattern for the assessment of 12 circulating metabolic miRNA expression levels (determined a priori by quantitative reverse transcriptase-polymerase chain reaction), plasma glucose, insulin, interleukin-6, tumor necrosis factor-α, C-reactive protein (CRP), adiponectin, glucagon-like peptide-1, and branched-chain amino acids. RESULTS: Of the 12 miRNAs, miR-15b-5p expression was higher following BEEF versus PLANT (P = 0.024). Increased miR-15b-5p expression correlated with decreased fasting CRP (r = -0.494; P = 0.086) and insulin concentrations (r = -0.670; P = 0.017). miR-15b-5p was inversely correlated with insulin resistance (r = -0.642; P = 0.024) and ß cell function (r = -0.646; P = 0.023) and positively correlated with markers of insulin sensitivity (r = 0.520; P = 0.083). However, the correlations were only observed following BEEF, not PLANT. CONCLUSIONS: These data indicate that the short-term intake of fresh, lean beef as part of a healthy dietary pattern impacts potential biomarkers of cardiometabolic health that are associated with cardiometabolic risk factors in women with overweight. This study was registered at clinicaltrials.gov as NCT02614729.