Allergy-associated biomarkers in early life identified by Omics techniques

The prevalence and severity of allergic diseases have increased over the last 30 years. Understanding the mechanisms responsible for these diseases is a major challenge in current allergology, as it is crucial for the transition towards precision medicine, which encompasses predictive, preventive, and personalized strategies. The urge to identify predictive biomarkers of allergy at early stages of life is crucial, especially in the context of major allergic diseases such as food allergy and atopic dermatitis. Identifying these biomarkers could enhance our understanding of the immature immune responses, improve allergy handling at early ages and pave the way for preventive and therapeutic approaches. This minireview aims to explore the relevance of three biomarker categories (proteome, microbiome, and metabolome) in early life. First, levels of some proteins emerge as potential indicators of mucosal health and metabolic status in certain allergic diseases. Second, bacterial taxonomy provides insight into the composition of the microbiota through high-throughput sequencing methods. Finally, metabolites, representing the end products of bacterial and host metabolic activity, serve as early indicators of changes in microbiota and host metabolism. This information could help to develop an extensive identification of biomarkers in AD and FA and their potential in translational personalized medicine in early life

Further Insights into the Gut Microbiota of Cow’s Milk Allergic Infants: Analysis of Microbial Functionality and Its Correlation with Three Fecal Biomarkers

Cow’s milk allergy (CMA) is one of the most prevalent food allergies in children. Several studies have demonstrated that gut microbiota influences the acquisition of oral tolerance to food antigens at initial stages of life. Changes in the gut microbiota composition and/or functionality (i.e., dysbiosis) have been linked to inadequate immune system regulation and the emergence of pathologies. Moreover, omic sciences have become an essential tool for the analysis of the gut microbiota. On the other hand, the use of fecal biomarkers for the diagnosis of CMA has recently been reviewed, with fecal calprotectin, α-1 antitrypsin, and lactoferrin being the most relevant. This study aimed at evaluating functional changes in the gut microbiota in the feces of cow’s milk allergic infants (AI) compared to control infants (CI) by metagenomic shotgun sequencing and at correlating these findings with the levels of fecal biomarkers (α-1 antitrypsin, lactoferrin, and calprotectin) by an integrative approach. We have observed differences between AI and CI groups in terms of fecal protein levels and metagenomic analysis. Our findings suggest that AI have altered glycerophospholipid metabolism as well as higher levels of lactoferrin and calprotectin that could be explained by their allergic status.This research was funded by Instituto de Salud Carlos III (PI17/01087 and PI20/01366) and Fundación Sociedad Española de Alergia e Inmunología Clínica (FSEAIC_2016). It was co-funded by the European Regional Development Fund “Investing in your future” for the thematic network and co-operative research centers ARADyAL RD16/0006/0015 and RD16/0006/0026. T.B-T is supported by FPI-CEU predoctoral fellowship. D.B. acknowledges financial support from Instituto de Salud Carlos III (PI19/00044)

Unravelling the Gut Microbiota of Cow’s Milk–Allergic Infants, Their Mothers, and Their Grandmothers

The gut microbiome constitutes a highly complex ecosystem in which bacteria are the most prominent components. Around 70% of primary colonization of the gut microbiota is maternal in origin [1], and the first 1000 days of life are crucial for the development of the intestinal microbiota [2]. Despite its early formation, the gut microbiota is highly dynamic and dependent on host-associated confounding factors such as age, diet, antibiotics, lifestyle, and environmental conditions [3,4]. Alterations in gut microbiota have been described in people with different types of allergy, including cow’s milk allergy (CMA)This work was supported by Instituto de Salud Carlos III (PI17/01087) and Fundación Sociedad Española de Alergia e Inmunología Clínica (FSEAIC_2016). It was cofunded by the European Regional Development Fund “Investing in your future” for the Thematic Network and Co-operative Research Centers ARADyAL RD16/0006/0015 and RD16/0006/0026. It was additionally supported by the Ministry of Science, Innovation in Spain (PCI2018-092930), cofunded by the European program ERA HDHL - Nutrition & the Epigenome, project Dietary Intervention in Food Allergy: Microbiome, Epigenetic and Metabolomic interactions (DIFAMEM). DR and EZ-V acknowledge funding from the Spanish Ministry of Science, Innovation and Universities (RTI2018-095166-B-I00). CU acknowledges funding from the Spanish Ministry of Economy (SAF2017-90083-R). TCB-T thanks CEUInternational Doctoral School (CEINDO) for his fellowship

A body weight loss- and health-promoting gut microbiota is established after bariatric surgery in individuals with severe obesity

Obesity has reached an epidemic level worldwide, and bariatric surgery (BS) has been proven to be the most efficient therapy to reduce severe obesity-related comorbidities. Given that the gut microbiota plays a causal role in obesity development and that surgery may alter the gut environment, investigating the impact of BS on the microbiota in the context of severe obesity is important. Although, alterations at the level of total gut bacteria, total gene content and total metabolite content have started to be disentangled, a clear deficit exists regarding the analysis of the active fraction of the microbiota, which is the fraction that is most reactive to the BS. Here, active gut microbiota and associated metabolic functions were evaluated using shotgun proteomics and metabolomics in 40 severely obese volunteers. Samples from each volunteer were obtained under basal conditions, after a short high protein and calorie-restricted diet, and 1 and 3 months after BS, including laparoscopic surgery through Roux-en-Y Gastric Bypass or Sleeve Gastrectomy. The results revealed for the first time the most active microbes and metabolic flux distribution pre- and post-surgery and deciphered main differences in the way sugars and short-fatty acids are metabolized, demonstrating that less energy-generating and anaerobic metabolism and detoxification mechanisms are promoted post-surgery. A comparison with non-obese proteome data further signified different ways to metabolize sugars and produce short chain fatty acids and deficiencies in proteins involved in iron transport and metabolism in severely obese individuals compared to lean individuals.This work was funded by grants SAF2015-65878-R, BIO2017-85522-R, PID2019-105969GB-I00 and RTI2018-095166-B-I00 from the Ministry of Science, Innovation and Universities, by the Ministry of Science and Innovation, by the Instituto de Salud Carlos III (projects PIE14/00045 and AC17/00022), Fundación Agencia Española contra el Cáncer and Instituto de Salud Carlos III(projects ERA NET TRANSCAN-2 AC17/00022 and AECC 2017-1485), Generalitat Valenciana (project Prometeo/2018/A/133) and co-financed by the European Regional Development Fund (ERDF). The proteomic analysis was performed in the Proteomics Facility of The Spanish National Center for Biotechnology (CNB-CSIC) that belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019.Peer reviewe

Functional microbiome deficits associated with ageing: chronological age-threshold

Composition of the gut microbiota changes during ageing, but questions remain about whether age is also associated with deficits in microbiome function and whether these changes occur sharply or progressively. The ability to define these deficits in populations of different ages may help determine a chronological age threshold at which deficits occur and subsequently identify innovative dietary strategies for active and healthy ageing. Here, active gut microbiota and associated metabolic functions were evaluated using shotgun proteomics in three well‐defined age groups consisting of 30 healthy volunteers, namely, ten infants, ten adults and ten elderly individuals. Samples from each volunteer at intervals of up to 6 months (n = 83 samples) were used for validation. Ageing gradually increases the diversity of gut bacteria that actively synthesize proteins, that is by 1.4‐fold from infants to elderly individuals. An analysis of functional deficits consistently identifies a relationship between tryptophan and indole metabolism and ageing (p .987) and progressively decrease with age (r2 > .948). An age threshold for a 50% decrease is observed ca. 11–31 years old, and a greater than 90% reduction is observed from the ages of 34–54 years. Based on recent investigations linking tryptophan with abundance of indole and other “healthy” longevity molecules and on the results from this small cohort study, dietary interventions aimed at manipulating tryptophan deficits since a relatively “young” age of 34 and, particularly, in the elderly are recommended.S.R. was recipient of a postdoctoral “Sara Borrell” contract from the Instituto de Salud Carlos III. This work was funded by grants SAF2015‐65878‐R and RTI2018‐095166‐B‐I00 from the Ministry of Science, Innovation and Universities with the cofunds of the European Regional Development Fund (ERDF) and the Agencia Estatal de Investigación (AEI), grant PIE14/00045 from the Instituto de Salud Carlos III, grant AC17/00022 from the Instituto de Salud Carlos III and Fundación Agencia Española contra el Cáncer (AECC) within the ERA NET TRANSCAN‐2, grant 2017‐1485 from the AECC and grant Prometeo/2018/A/133 from the Generalitat Valenciana. M.F. acknowledges the support of BIO2017‐85522‐R, from the Ministry of Science, Innovation and Universities, with the cofunds of the ERDF and the Agencia Estatal de Investigación (AEI). The proteomic analysis was performed in the Proteomics Facility of The Spanish National Center for Biotechnology (CNB‐CSIC) that belongs to ProteoRed, PRB3‐ISCIII, supported by grant PT17/0019. The funding bodies did not have a role in the design or conduct of the study, the analysis and interpretation of the results, the writing of the report, or the decision to publish