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Augustine T, Murugesan S, Badri F, Gentilcore G, Grivel JC, Akobeng A, Elawad M, Adeli M, Al Khodor S, van Panhuys N. Immunoglobulin-coating patterns reveal altered humoral responses to gut bacteria in pediatric cow milk allergies. J Transl Med 2024; 22:1021. [PMID: 39533360 PMCID: PMC11558889 DOI: 10.1186/s12967-024-05850-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 10/31/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Pediatric cow milk allergies (CMA) can occur in immunoglobulin (Ig) E and non-IgE-mediated forms. Unlike IgE-mediated allergies, the mechanisms of disease pathogenesis in non-IgE-mediated food allergy and an association with microbiome has not been well established. Previous studies have identified the presence of altered humoral responses to gut bacteria in IgE mediated allergies. Here, we analyzed IgA, IgE and IgG responses to gut bacteria in subjects with either IgE or non-IgE mediated CMA to identify relative proportions of Ig-coated bacteria and characterize unique disease specific microbial signatures. METHODS Multi-parametric flow cytometry analysis was used to identify IgA, IgE and IgG responses to gut bacteria in CMA patients. Cell sorting of Ig coated gut bacteria was subsequently performed followed by high throughput 16S rRNA gene sequencing and specific patterns of humoral responses to gut bacteria assessed in each study group. RESULTS We identified significant alterations in IgA and IgG gut bacterial coating patterns in CMA subjects. Proportions of IgA-coated bacteria were decreased in IgE mediated CMA subjects without atopic dermatitis (ALL) and non-IgE mediated CMA subjects (ENP), compared to healthy controls (CON). In comparison, IgG-coated bacteria was significantly elevated in CMA subjects with atopic dermatitis (AD). Alpha and beta diversities displayed significant differences in IgA-, IgE-, and IgG-coated bacteria in AD and ENP groups. Significant differences in bacteria coated by IgA, IgE and IgG were detected at Phyla, Genus and Species levels and associated bacterial dysbiosis in IgE and non-IgE mediated allergies were identified. Linear discriminant analysis (LDA) effect size (LEFse) revealed unique disease associated bacterial signatures, including several pathogenic bacteria namely Bacteroides fragilis, Ruminococcus gnavus, Eubacterium dolichum, Fusobacterium, Clostridium neonatale and Robinsoniella peoriensis. Receiver operating characteristic curve analysis confirmed the efficiency of using the bacterial signatures identified as biomarkers for disease. CONCLUSIONS Altered IgA and IgG responses to gut bacteria were identified in CMA subjects. The disease-specific responses were associated with alterations in bacterial diversity and concomitant dysbiosis of Ig-coated bacteria in IgE-mediated and non-IgE-mediated CMA pediatric subjects. The identification of pathogenic bacteria uniquely associated with different classes of allergic disease indicates a role of these bacteria in driving disease-specific pathological phenotypes.
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Affiliation(s)
| | | | - Fariada Badri
- Laboratory of Immunoregulation, Sidra Medicine, Doha, Qatar
| | | | | | | | - Mamoun Elawad
- Department of Gastroenterology, Sidra Medicine, Doha, Qatar
| | - Mehdi Adeli
- Department of Allergy/Immunology, Sidra Medicine, Doha, Qatar
| | - Souhaila Al Khodor
- Microbiome and Host-Microbes Interactions Laboratory, Sidra Medicine, Doha, Qatar
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Kalashnikova IG, Nekrasova AI, Korobeynikova AV, Bobrova MM, Ashniev GA, Bakoev SY, Zagainova AV, Lukashina MV, Tolkacheva LR, Petryaikina ES, Nekrasov AS, Mitrofanov SI, Shpakova TA, Frolova LV, Bulanova NV, Snigir EA, Mukhin VE, Yudin VS, Makarov VV, Keskinov AA, Yudin SM. The Association between Gut Microbiota and Serum Biomarkers in Children with Atopic Dermatitis. Biomedicines 2024; 12:2351. [PMID: 39457662 PMCID: PMC11505256 DOI: 10.3390/biomedicines12102351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 10/10/2024] [Accepted: 10/12/2024] [Indexed: 10/28/2024] Open
Abstract
Background. Currently, it is known that the gut microbiota plays an important role in the functioning of the immune system, and a rebalancing of the bacterial community can arouse complex immune reactions and lead to immune-mediated responses in an organism, in particular, the development of atopic dermatitis (AD). Cytokines and chemokines are regulators of the innate and adaptive immune response and represent the most important biomarkers of the immune system. It is known that changes in cytokine profiles are a hallmark of many diseases, including atopy. However, it remains unclear how the bacterial imbalance disrupts the function of the immune response in AD. Objectives. We attempted to determine the role of gut bacteria in modulating cytokine pathways and their role in atopic inflammation. Methods. We sequenced the 16S rRNA gene from 50 stool samples of children aged 3-12 years who had confirmed atopic dermatitis, and 50 samples from healthy children to serve as a control group. To evaluate the immune status, we conducted a multiplex immunofluorescence assay and measured the levels of 41 cytokines and chemokines in the serum of all participants. Results. To find out whether changes in the composition of the gut microbiota were significantly associated with changes in the level of inflammatory cytokines, a correlation was calculated between each pair of bacterial family and cytokine. In the AD group, 191 correlations were significant (Spearman's correlation coefficient, p ≤ 0.05), 85 of which were positive and 106 which were negative. Conclusions. It has been demonstrated that intestinal dysbiosis is associated with alterations in cytokine profiles, specifically an increase in proinflammatory cytokine concentrations. This may indicate a systemic impact of these conditions, leading to an imbalance in the immune system's response to the Th2 type. As a result, atopic conditions may develop. Additionally, a correlation between known AD biomarkers (IL-5, IL-8, IL-13, CCL22, IFN-γ, TNF-α) and alterations in the abundance of bacterial families (Pasteurellaceae, Barnesiellaceae, Eubacteriaceae) was observed.
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Affiliation(s)
- Irina G. Kalashnikova
- Federal State Budgetary Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical and Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.I.N.); (A.V.K.); (M.M.B.); (G.A.A.); (S.Y.B.); (A.V.Z.); (M.V.L.); (L.R.T.); (E.S.P.); (A.S.N.); (S.I.M.); (T.A.S.); (L.V.F.); (N.V.B.); (E.A.S.); (V.E.M.); (V.S.Y.); (V.V.M.); (A.A.K.); (S.M.Y.)
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Farnetano M, Carucci L, Coppola S, Oglio F, Masino A, Cozzolino M, Nocerino R, Berni Canani R. Gut microbiome features in pediatric food allergy: a scoping review. FRONTIERS IN ALLERGY 2024; 5:1438252. [PMID: 39386092 PMCID: PMC11461474 DOI: 10.3389/falgy.2024.1438252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Accepted: 08/13/2024] [Indexed: 10/12/2024] Open
Abstract
Increasing evidence suggests that alterations in the gut microbiome (GM) play a pivotal role in the pathogenesis of pediatric food allergy (FA). This scoping review analyzes the current evidence on GM features associated with pediatric FAs and highlights the importance of the GM as a potential target of intervention for preventing and treating this common condition in the pediatric age. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we searched PubMed and Embase using the keywords (gut microbiome OR dysbiosis OR gut microbiota OR microbiome signatures) AND (food allergy OR IgE-mediated food allergy OR food protein-induced allergic proctocolitis OR food protein-induced enterocolitis OR non-IgE food allergy OR cow milk allergy OR hen egg allergy OR peanut allergy OR fish allergy OR shellfish allergy OR tree nut allergy OR soy allergy OR wheat allergy OR rice allergy OR food sensitization). We included 34 studies reporting alterations in the GM in children affected by FA compared with healthy controls. The GM in pediatric FAs is characterized by a higher abundance of harmful microorganisms (e.g., Enterobacteriaceae, Clostridium sensu stricto, Ruminococcus gnavus, and Blautia spp.) and lower abundance of beneficial bacteria (e.g., Bifidobacteriaceae, Lactobacillaceae, some Bacteroides species). Moreover, we provide an overview of the mechanisms of action elicited by these bacterial species in regulating immune tolerance and of the main environmental factors that can modulate the composition and function of the GM in early life. Altogether, these data improve our knowledge of the pathogenesis of FA and can open the way to innovative diagnostic, preventive, and therapeutic strategies for managing these conditions.
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Affiliation(s)
- Margherita Farnetano
- Department of Translational Medical Science, University of Naples Federico II, Naples, Italy
| | - Laura Carucci
- Department of Translational Medical Science, University of Naples Federico II, Naples, Italy
- ImmunoNutritionLab at the CEINGE Advanced Biotechnologies Research Center, University of Naples Federico II, Naples, Italy
| | - Serena Coppola
- Department of Translational Medical Science, University of Naples Federico II, Naples, Italy
- ImmunoNutritionLab at the CEINGE Advanced Biotechnologies Research Center, University of Naples Federico II, Naples, Italy
| | - Franca Oglio
- Department of Translational Medical Science, University of Naples Federico II, Naples, Italy
- ImmunoNutritionLab at the CEINGE Advanced Biotechnologies Research Center, University of Naples Federico II, Naples, Italy
| | - Antonio Masino
- Department of Translational Medical Science, University of Naples Federico II, Naples, Italy
- ImmunoNutritionLab at the CEINGE Advanced Biotechnologies Research Center, University of Naples Federico II, Naples, Italy
| | - Marica Cozzolino
- Department of Translational Medical Science, University of Naples Federico II, Naples, Italy
- ImmunoNutritionLab at the CEINGE Advanced Biotechnologies Research Center, University of Naples Federico II, Naples, Italy
| | - Rita Nocerino
- Department of Translational Medical Science, University of Naples Federico II, Naples, Italy
- ImmunoNutritionLab at the CEINGE Advanced Biotechnologies Research Center, University of Naples Federico II, Naples, Italy
- Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy
| | - Roberto Berni Canani
- Department of Translational Medical Science, University of Naples Federico II, Naples, Italy
- ImmunoNutritionLab at the CEINGE Advanced Biotechnologies Research Center, University of Naples Federico II, Naples, Italy
- Task Force on Microbiome Studies, University of Naples Federico II, Naples, Italy
- European Laboratory for the Investigation of Food-Induced Diseases, University of Naples Federico II, Naples, Italy
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Shi J, Dong P, Liu C, Xu Y, Zheng M, Cheng L, Wang J, Raghavan V. Lactobacillus rhamnosus Probio-M9 alleviates OVA-sensitized food allergy through modulating gut microbiota and its metabolism. Food Funct 2023; 14:10784-10795. [PMID: 37982421 DOI: 10.1039/d3fo03321j] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2023]
Abstract
Over the past few decades, food allergy has continued to rise, significantly affecting our health, economy, and quality of life. However, current therapeutic strategies have limited efficacy and need to be improved. One alternative to prevent or reduce allergies is to modulate immunity and microbiota. Human milk (HM) could be considered a protective factor against food allergy, but how probiotics in human milk impact the susceptibility to food allergy remains unknown. Therefore, we studied the preventive impact of human milk Lactobacillus rhamnosus Probio-M9 on food allergy in ovalbumin (OVA)-sensitized mice. We studied the effects of oral administration of Probio-M9 on allergic signatures, immune response, gut microbiota, and metabolism. Oral therapeutic administration of live Probio-M9, but not heat-killed Probio-M9, significantly reduces OVA-specific IgE (OVA-sIgE), histamine, and mMCP-1 (mouse mast cell protease-1) levels in OVA-sensitized mice. Moreover, Probio-M9 supplementation reduced allergic inflammation and changes in the Th2/Th1 balance toward a dampened Th2 response. 16S rDNA sequencing analysis revealed an increased ratio of Firmicutes/Bacteroidota (F/B) and the relative abundance of short-chain fatty acid (SCFA)-producing Clostridia in the feces after Probio-M9 intake. Simultaneously, Probio-M9 significantly increased the levels of SCFAs and promoted the phosphorylation of signal transducer and activator of transcription 3 (STAT3), thereby inducing the expression of the antimicrobial peptides (AMPs) Reg3b and Reg3g. Our findings suggest that the use of Probio-M9 can be a potent strategy in food allergy prevention.
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Affiliation(s)
- Jialu Shi
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China.
| | - Pengfei Dong
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China
| | - Cheng Liu
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China.
| | - Yan Xu
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China.
| | - Mingzhu Zheng
- Department of Microbiology and Immunology School of Medicine, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Southeast University, Nanjing, Jiangsu 210009, China
| | - Lei Cheng
- Department of Otorhinolaryngology and Clinical Allergy Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Jin Wang
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China.
| | - Vijaya Raghavan
- Department of Bioresource Engineering, Faculty of Agricultural and Environmental Sciences, McGill University, 21111 Lakeshore Rd, Sainte-Anne-de-Bellevue, QC H9X3V9, Canada
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Mahdavinia M, Fyolek JP, Jiang J, Thivalapill N, Bilaver LA, Warren C, Fox S, Nimmagadda SR, Newmark PJ, Sharma H, Assa'ad A, Seed PC, Gupta RS. Gut microbiome is associated with asthma and race in children with food allergy. J Allergy Clin Immunol 2023; 152:1541-1549.e1. [PMID: 37714436 PMCID: PMC10872992 DOI: 10.1016/j.jaci.2023.07.024] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 06/30/2023] [Accepted: 07/27/2023] [Indexed: 09/17/2023]
Abstract
BACKGROUND The composition of the gut microbiome has been associated with development of atopic conditions such as food allergy (FA) and asthma. African American or Black children with FA have higher rate of asthma compared to their White counterparts. OBJECTIVE We sought to investigate whether the diversity and relative abundance (RA) of gut microbiota is different between children with FA from different racial backgrounds living in the same cities. Furthermore, we aimed to understand whether the difference in the gut microbiota is associated with asthma in children with FA. METHODS We analyzed and compared the stool microbiome of a cohort of Black and White children with FA by shotgun genomic sequencing. RESULTS A total of 152 children with IgE-mediated FA enrolled onto FORWARD (Food Allergy Outcomes Related to White and African American Racial Differences); 30 Black and 122 White children were included. The RA of several bacteria was associated with race and asthma. Most notably the RA of Bacteroides thetaiotaomicron, Chlamydia thrachomatis, Parabacteroides goldsteinii, and Bacteroides eggerthii were significantly higher, while the RA of Bifidobacterium sp CAG:754, Parabacterium johnsonii, Bacteroides intestinalis, and Bifidobacterium breve were significantly lower in stool samples of Black children compared to White children. Asthma was associated with lower RA of B breve, Bifidobacterium catenulatum, Prevotella copri, Veilloella sp CAG:933, and Bacteroides plebius, and higher RA of 3 Bacteroides species. CONCLUSIONS The observed variations in the gut microbiota of Black and White children such as differences in the Bacteroides and Bifidobacterium species along with their association to history of asthma in our cohort is indicative of their potential role in the higher rate of asthma observed among Black children with FA.
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Affiliation(s)
- Mahboobeh Mahdavinia
- Division of Allergy and Immunology, Department of Medicine and Department of Pediatrics, Rush University Medical Center, Chicago, Ill.
| | - John P Fyolek
- Center for Food Allergy and Asthma Research and Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill
| | - Jialing Jiang
- Center for Food Allergy and Asthma Research and Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill
| | - Neil Thivalapill
- Center for Food Allergy and Asthma Research and Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill
| | - Lucy A Bilaver
- Center for Food Allergy and Asthma Research and Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill
| | - Christopher Warren
- Center for Food Allergy and Asthma Research and Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill
| | - Susan Fox
- Division of Allergy and Immunology, Department of Medicine and Department of Pediatrics, Rush University Medical Center, Chicago, Ill
| | - Sai R Nimmagadda
- Center for Food Allergy and Asthma Research and Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill
| | - Pamela J Newmark
- Center for Food Allergy and Asthma Research and Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill
| | - Hemant Sharma
- Division of Allergy and Immunology, Children's National Health Systems, Washington, DC
| | - Amal Assa'ad
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, and the University of Cincinnati, Cincinnati, Ohio
| | - Patrick C Seed
- Division of Infectious Disease, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill
| | - Ruchi S Gupta
- Center for Food Allergy and Asthma Research and Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill
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Moak R, Boone N, Eidson N, Rohrer A, Engevik M, Williams K, Chetta K. Exploring the links between necrotizing enterocolitis and cow's milk protein allergy in preterm infants: a narrative review. Front Pediatr 2023; 11:1274146. [PMID: 38027265 PMCID: PMC10663262 DOI: 10.3389/fped.2023.1274146] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 10/17/2023] [Indexed: 12/01/2023] Open
Abstract
A broad range of allergic disorders and intolerance are associated with cow's milk protein in the infant diet. Allergy and intolerance to cow's milk proteins are commonly recognized in the healthy term infant, and the prevalence cow's milk protein intolerance (CMPI) varies widely but 5 challenge confirmed studies free from selection bias ranged from 1.9%-4.9%. These disorders are classified by the presence of IgE, non-IgE or T-cell-mediated signaling. Additionally, the severity of these adverse food reactions can range from mild gastrointestinal symptoms to severe sepsis-like episodes, as in the case of food protein-induced enterocolitis syndrome (FPIES). Food protein-induced intolerance in the healthy young infant lies in stark contrast to enterocolitis that typically occurs in the preterm neonate. Necrotizing enterocolitis (NEC) is a distinct progressive disease process, usually characterized by a high mortality rate, with a risk of death from 30% to 50%. While its exact etiology is unclear, its main triggers include formula (cow's milk protein), hypoxia, perfusion-related issues, and unregulated inflammation in the premature intestine. The distinction between NEC and cow's milk protein intolerance is difficult to discern in some cases. In the late preterm population, infants with colitis can have both NEC and cow's milk intolerance on the differential. In infants with multiple episodes of mild NEC, cow's milk protein intolerance may be the underlying diagnosis. In this review, we compare the pathophysiological characteristics, diagnosis and treatment of disorders of cow's milk protein intolerance with the entity of preterm NEC. This review highlights similarities in both entities and may inspire future cross-disciplinary research.
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Affiliation(s)
- Rosemary Moak
- Department of Internal Medicine, Medical University of South Carolina, Charleston, SC, United States
| | - Neal Boone
- Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Medical University of South Carolina, Charleston, SC, United States
| | - Natalie Eidson
- Department of Pediatrics, Medical University of South Carolina, Charleston, SC, United States
| | - Allison Rohrer
- Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Medical University of South Carolina, Charleston, SC, United States
| | - Mindy Engevik
- Department of Regenerative Medicine & Cell Biology, Medical University of South Carolina, Charleston, SC, United States
- Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, SC, United States
| | - Kelli Williams
- Department of Pediatrics, Division of Pediatric Pulmonology, Allergy and Immunology, Medical University of South Carolina, Charleston, SC, United States
| | - Katherine Chetta
- Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Medical University of South Carolina, Charleston, SC, United States
- C.P. Darby Children’s Research Institute, Medical University of South Carolina, Shawn Jenkins Children’s Hospital, Charleston, SC, United States
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Elizalde-Torrent A, Borgognone A, Casadellà M, Romero-Martin L, Escribà T, Parera M, Rosales-Salgado Y, Díaz-Pedroza J, Català-Moll F, Noguera-Julian M, Brander C, Paredes R, Olvera A. Vaccination with an HIV T-Cell Immunogen (HTI) Using DNA Primes Followed by a ChAdOx1-MVA Boost Is Immunogenic in Gut Microbiota-Depleted Mice despite Low IL-22 Serum Levels. Vaccines (Basel) 2023; 11:1663. [PMID: 38005995 PMCID: PMC10675013 DOI: 10.3390/vaccines11111663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 10/25/2023] [Accepted: 10/26/2023] [Indexed: 11/26/2023] Open
Abstract
Despite the important role of gut microbiota in the maturation of the immune system, little is known about its impact on the development of T-cell responses to vaccination. Here, we immunized C57BL/6 mice with a prime-boost regimen using DNA plasmid, the Chimpanzee Adenovirus, and the modified Vaccinia Ankara virus expressing a candidate HIV T-cell immunogen and compared the T-cell responses between individuals with an intact or antibiotic-depleted microbiota. Overall, the depletion of the gut microbiota did not result in significant differences in the magnitude or breadth of the immunogen-specific IFNγ T-cell response after vaccination. However, we observed marked changes in the serum levels of four cytokines after vaccinating microbiota-depleted animals, particularly a significant reduction in IL-22 levels. Interestingly, the level of IL-22 in serum correlated with the abundance of Roseburia in the large intestine of mice in the mock and vaccinated groups with intact microbiota. This short-chain fatty acid (SCFA)-producing bacterium was significantly reduced in the vaccinated, microbiota-depleted group. Therefore, our results indicate that, although microbiota depletion reduces serum levels of IL-22, the powerful vaccine regime used could have overcome the impact of microbiota depletion on IFNγ-producing T-cell responses.
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Affiliation(s)
- Aleix Elizalde-Torrent
- Irsicaixa—AIDS Research Institute, 08916 Barcelona, Spain; (A.E.-T.); (A.B.); (M.C.); (L.R.-M.); (T.E.); (M.P.); (F.C.-M.); (M.N.-J.); (C.B.); (R.P.)
| | - Alessandra Borgognone
- Irsicaixa—AIDS Research Institute, 08916 Barcelona, Spain; (A.E.-T.); (A.B.); (M.C.); (L.R.-M.); (T.E.); (M.P.); (F.C.-M.); (M.N.-J.); (C.B.); (R.P.)
| | - Maria Casadellà
- Irsicaixa—AIDS Research Institute, 08916 Barcelona, Spain; (A.E.-T.); (A.B.); (M.C.); (L.R.-M.); (T.E.); (M.P.); (F.C.-M.); (M.N.-J.); (C.B.); (R.P.)
| | - Luis Romero-Martin
- Irsicaixa—AIDS Research Institute, 08916 Barcelona, Spain; (A.E.-T.); (A.B.); (M.C.); (L.R.-M.); (T.E.); (M.P.); (F.C.-M.); (M.N.-J.); (C.B.); (R.P.)
- Departament de Biologia Cellular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona (UAB), 08193 Cerdanyola del Valles, Spain
| | - Tuixent Escribà
- Irsicaixa—AIDS Research Institute, 08916 Barcelona, Spain; (A.E.-T.); (A.B.); (M.C.); (L.R.-M.); (T.E.); (M.P.); (F.C.-M.); (M.N.-J.); (C.B.); (R.P.)
| | - Mariona Parera
- Irsicaixa—AIDS Research Institute, 08916 Barcelona, Spain; (A.E.-T.); (A.B.); (M.C.); (L.R.-M.); (T.E.); (M.P.); (F.C.-M.); (M.N.-J.); (C.B.); (R.P.)
| | - Yaiza Rosales-Salgado
- Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), 08916 Badalona, Spain; (Y.R.-S.); (J.D.-P.)
| | - Jorge Díaz-Pedroza
- Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), 08916 Badalona, Spain; (Y.R.-S.); (J.D.-P.)
| | - Francesc Català-Moll
- Irsicaixa—AIDS Research Institute, 08916 Barcelona, Spain; (A.E.-T.); (A.B.); (M.C.); (L.R.-M.); (T.E.); (M.P.); (F.C.-M.); (M.N.-J.); (C.B.); (R.P.)
| | - Marc Noguera-Julian
- Irsicaixa—AIDS Research Institute, 08916 Barcelona, Spain; (A.E.-T.); (A.B.); (M.C.); (L.R.-M.); (T.E.); (M.P.); (F.C.-M.); (M.N.-J.); (C.B.); (R.P.)
- Facultat de Medicina, Universitat de Vic—Universitat Central de Catalunya (UVic-UCC), 08500 Vic, Spain
- CIBERINFEC—ISCIII, 28029 Madrid, Spain
| | - Christian Brander
- Irsicaixa—AIDS Research Institute, 08916 Barcelona, Spain; (A.E.-T.); (A.B.); (M.C.); (L.R.-M.); (T.E.); (M.P.); (F.C.-M.); (M.N.-J.); (C.B.); (R.P.)
- Facultat de Medicina, Universitat de Vic—Universitat Central de Catalunya (UVic-UCC), 08500 Vic, Spain
- CIBERINFEC—ISCIII, 28029 Madrid, Spain
- Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain
- Aelix Therapeutics, 08028 Barcelona, Spain
| | - Roger Paredes
- Irsicaixa—AIDS Research Institute, 08916 Barcelona, Spain; (A.E.-T.); (A.B.); (M.C.); (L.R.-M.); (T.E.); (M.P.); (F.C.-M.); (M.N.-J.); (C.B.); (R.P.)
- Facultat de Medicina, Universitat de Vic—Universitat Central de Catalunya (UVic-UCC), 08500 Vic, Spain
- CIBERINFEC—ISCIII, 28029 Madrid, Spain
- Center for Global Health and Diseases, Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
- Fight AIDS Foundation, Infectious Diseases Department, Germans Trias i Pujol University Hospital, 08916 Badalona, Spain
- Department of Infectious Diseases Service, Germans Trias i Pujol University Hospital, 08916 Badalona, Spain
| | - Alex Olvera
- Irsicaixa—AIDS Research Institute, 08916 Barcelona, Spain; (A.E.-T.); (A.B.); (M.C.); (L.R.-M.); (T.E.); (M.P.); (F.C.-M.); (M.N.-J.); (C.B.); (R.P.)
- CIBERINFEC—ISCIII, 28029 Madrid, Spain
- Facultat de Ciències, Tecnologia i Enginyeries, Universitat de Vic—Universitat Central de Catalunya (UVic-UCC), 08500 Vic, Spain
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Noli C, Varina A, Barbieri C, Pirola A, Olivero D. Analysis of Intestinal Microbiota and Metabolic Pathways before and after a 2-Month-Long Hydrolyzed Fish and Rice Starch Hypoallergenic Diet Trial in Pruritic Dogs. Vet Sci 2023; 10:478. [PMID: 37505882 PMCID: PMC10384699 DOI: 10.3390/vetsci10070478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 07/14/2023] [Accepted: 07/18/2023] [Indexed: 07/29/2023] Open
Abstract
Intestinal microbiota alterations were described in allergic individuals and may improve with diets. Farmina Ultra Hypo (FUH), a hydrolyzed fish/rice starch hypoallergenic diet, is able to improve clinical signs in allergic dogs. Study objectives were to determine microbiota differences in allergic dogs before and after feeding with FUH for eight weeks. Forty skin allergic dogs were evaluated clinically before and after the diet. Unresponsive dogs were classified as canine atopic dermatitis (CAD); responsive dogs relapsing after challenge with previous foods were classified as being food reactive (AFR), and those not relapsing as doubtful (D). Sequencing of feces collected pre- and post-diet was performed, with comparisons between and within groups, pre- and post-diet, and correlations to possible altered metabolic pathways were sought. Microbiota in all dogs was dominated by Bacteroidota, Fusobacteriota, Firmicutes and Proteobacteria, albeit with large interindividual variations and with some prevalence changes after the diet. In general, bacteria producing short-chain fatty acids were increased in all samples. CAD dogs showed pre-and post-diet microbiota patterns different from the other two groups. Bacteria taxa were enriched post-diet only in the AFR group. Changes in metabolic pathways were observed mainly in the CAD group. FUH may be able to improve intestinal microbiota and thus clinical signs of skin allergy.
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Affiliation(s)
- Chiara Noli
- Servizi Dermatologici Veterinari, Strada Bedale della Ressia 2, 12016 Peveragno, Italy
| | - Antonella Varina
- Ambulatorio Veterinario Varina-Ghidella-Scarfone, Via Fréjus 54, 10139 Torino, Italy
| | | | | | - Daniela Olivero
- Laboratorio Analisi Veterinarie BiEsseA Scilvet, Via Amedeo d'Aosta 7, 20129 Milano, Italy
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9
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Muniz AKOA, Vianna EO, Padilha LL, Nascimento JXPT, Batista RFL, Barbieri MA, Bettiol H, Ribeiro CCC. Sugar-Sweetened Beverages and Allergy Traits at Second Year of Life: BRISA Cohort Study. Nutrients 2023; 15:3218. [PMID: 37513636 PMCID: PMC10383806 DOI: 10.3390/nu15143218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 07/16/2023] [Accepted: 07/16/2023] [Indexed: 07/30/2023] Open
Abstract
Sugar-Sweetened Beverage (SSBs) consumption has risen in early life and it is plausible that it might increase children's risk of allergies. In this paper, we analyzed the association of SSB consumption with allergies in children's second year of life. This study analyzed data from a São Luís BRISA prenatal cohort in the follow-up of children (n = 1144) in their second year of life. Allergy Traits were a latent variable deduced from medical diagnoses of allergic rhinitis, atopic dermatitis, and food allergies. SSBs were investigated as a percentage of daily calories based on 24 h recalls, including industrialized fruit juices, soft drinks, and ready-made chocolate milk. Other variables analyzed were socioeconomic status, age, body mass index z-score, episodes of diarrhea, and breastfeeding. Our finds were that higher consumption of daily calories from SSBs was associated with higher Allergy Trait values (SC = 0.174; p = 0.025); older age (SC = -0.181; p = 0.030) was associated with lower Allergy Trait values; and episodes of diarrhea were correlated with Allergy Traits (SC = 0.287; p = 0.015). SSB exposure was associated with Allergy Traits in children's second year of life; thus, abstaining from these beverages may also confer additional advantages in curtailing allergic diseases during early childhood.
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Affiliation(s)
| | - Elcio Oliveira Vianna
- Ribeirão Preto Medical School, University of São Paulo-USP, Ribeirao Preto 14049-900, Sao Paulo, Brazil
| | - Luana Lopes Padilha
- Postgraduate Program in Public Health, Department of Public Health, Federal University of Maranhão-UFMA, Sao Luis 65020-060, Maranhao, Brazil
| | | | - Rosangela Fernandes Lucena Batista
- Postgraduate Program in Public Health, Department of Public Health, Federal University of Maranhão-UFMA, Sao Luis 65020-060, Maranhao, Brazil
| | - Marco Antonio Barbieri
- Ribeirão Preto Medical School, University of São Paulo-USP, Ribeirao Preto 14049-900, Sao Paulo, Brazil
| | - Heloisa Bettiol
- Ribeirão Preto Medical School, University of São Paulo-USP, Ribeirao Preto 14049-900, Sao Paulo, Brazil
| | - Cecilia Claudia Costa Ribeiro
- Postgraduate Program in Public Health, Department of Public Health, Federal University of Maranhão-UFMA, Sao Luis 65020-060, Maranhao, Brazil
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10
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Chen C, Liu C, Zhang K, Xue W. The role of gut microbiota and its metabolites short-chain fatty acids in food allergy. FOOD SCIENCE AND HUMAN WELLNESS 2023. [DOI: 10.1016/j.fshw.2022.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
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11
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Duan C, Ma L, Yu J, Sun Y, Liu L, Ma F, Li X, Li D. Oral administration of Lactobacillus plantarum JC7 alleviates OVA-induced murine food allergy through immunoregulation and restoring disordered intestinal microbiota. Eur J Nutr 2023; 62:685-698. [PMID: 36194269 PMCID: PMC9530419 DOI: 10.1007/s00394-022-03016-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 09/22/2022] [Indexed: 12/17/2022]
Abstract
PURPOSE The incidence and prevalence of food allergy have sharply risen over the past several decades. Oral administration of probiotic stains has been proven as a safe and effective method to control food allergy. In this study, it aims to comprehensively investigate the anti-allergic effect of Lactobacillus plantarum JC7. METHODS Balb/c mice were randomly divided into three groups and received OVA (20 µg/mouse, intraperitoneal injection), L. plantarum JC7 (2 × 108 CFU/mouse, intragastric administration) + OVA (20 µg/mouse, intraperitoneal injection) or 0.9% saline (intragastric administration) for 3 weeks. Body weight was monitored weekly, and allergic reactions were evaluated after challenge of OVA. Serum levels of OVA-specific immunoglobulins and various cytokines were tested using ELISA, and the cecum microbiota was analysed by 16S rRNA sequencing to explore the relationships between these indicators and OVA-induced food allergy. Western blotting was used to identify the expression levels of phosphorylated IκBα and nuclear factor kappa B p65. RESULTS OVA-sensitised mice showed mitigation of respiratory manifestations, alleviation of lung inflammation and congestion, and the presence of an intact intestinal villus structure. Furthermore, OVA-specific immunoglobulin E (IgE), OVA-specific-IgG1, and plasma histamine levels were declined in mice treated with L. plantarum JC7 than in OVA-sensitised mice. In addition, interferon-γ (IFN-γ) and interleukin 10 (IL-10) levels were significantly increased, while IL-4 and IL-17A levels were clearly decreased in mice that had undergone oral administration of L. plantarum JC7, compared with OVA-sensitised mice. These findings indicated imbalances of T helper cell type 1 (Th1)/Th2 and regulatory T cells (Treg)/Th17, which were confirmed by quantitative polymerase chain reaction (PCR). Western blotting demonstrated that the expression levels of phosphorylated IκBα and nuclear factor kappa B p65 were significantly increased in OVA-sensitised mice, but these changes were partly reversed after treatment with L. plantarum JC7. Oral administration of L. plantarum JC7 increased the richness, diversity, and evenness of cecum microbiota, characterised by higher Bacteroidetes abundance and lower Firmicutes abundance. Additionally, the intestinal microbial community composition was significantly altered in the OVA-sensitised group, indicating a disordered intestinal microbiota that was restored by the oral administration of L. plantarum JC7. CONCLUSION Overall, L. plantarum JC7 can prevent food allergy by rectifying Th1/Th2 and Treg/Th17 imbalances, combined with modifications of disordered intestinal microbiota.
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Affiliation(s)
- Cuicui Duan
- Key Laboratory of Agro-Products Processing Technology, Jilin Provincial Department of Education, Changchun University, 6543 Weixing Road, Changchun, 130022 Jilin People’s Republic of China
| | - Lin Ma
- Key Laboratory of Agro-Products Processing Technology, Jilin Provincial Department of Education, Changchun University, 6543 Weixing Road, Changchun, 130022 Jilin People’s Republic of China
| | - Jie Yu
- Key Laboratory of Agro-Products Processing Technology, Jilin Provincial Department of Education, Changchun University, 6543 Weixing Road, Changchun, 130022 Jilin People’s Republic of China
| | - Yixue Sun
- Key Laboratory of Agro-Products Processing Technology, Jilin Provincial Department of Education, Changchun University, 6543 Weixing Road, Changchun, 130022 Jilin People’s Republic of China
| | - Lifan Liu
- Graduate School, Changchun University, 6543 Weixing Road, Changchun, 130022 Jilin People’s Republic of China
| | - Fumin Ma
- Key Laboratory of Agro-Products Processing Technology, Jilin Provincial Department of Education, Changchun University, 6543 Weixing Road, Changchun, 130022 Jilin People’s Republic of China
| | - Xiaolei Li
- Key Laboratory of Agro-Products Processing Technology, Jilin Provincial Department of Education, Changchun University, 6543 Weixing Road, Changchun, 130022 Jilin People’s Republic of China
| | - Dan Li
- Key Laboratory of Agro-Products Processing Technology, Jilin Provincial Department of Education, Changchun University, 6543 Weixing Road, Changchun, 130022, Jilin, People's Republic of China.
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12
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Kelly MS, Bunyavanich S, Phipatanakul W, Lai PS. The Environmental Microbiome, Allergic Disease, and Asthma. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2022; 10:2206-2217.e1. [PMID: 35750322 PMCID: PMC9704440 DOI: 10.1016/j.jaip.2022.06.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 05/24/2022] [Accepted: 06/03/2022] [Indexed: 04/26/2023]
Abstract
The environmental microbiome represents the entirety of the microbes and their metabolites that we encounter in our environments. A growing body of evidence supports the role of the environmental microbiome in risk for and severity of allergic diseases and asthma. The environmental microbiome represents a ubiquitous, lifelong exposure to non-self antigens. During the critical window between birth and 1 year of life, interactions between our early immune system and the environmental microbiome have 2 consequences: our individual microbiome is populated by environmental microbes, and our immune system is trained regarding which antigens to tolerate. During this time, a diversity of exposures appears largely protective, dramatically decreasing the risk of developing allergic diseases and asthma. As we grow older, our interactions with the environmental microbiome change. While it continues to exert influence over the composition of the human microbiome, the environmental microbiome becomes increasingly a source for antigenic stimulation and infection. The same microbial exposure protective against disease development may exacerbate disease severity. Although much has been learned about the importance of the environmental microbiome in allergic disease, much more remains to be understood about these complicated interactions between our environment, our microbiome, our immune system, and disease.
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Affiliation(s)
- Michael S Kelly
- Department of Internal Medicine, Massachusetts General Hospital, Boston, Mass; Harvard Medical School, Boston, Mass
| | - Supinda Bunyavanich
- Division of Allergy and Immunology, Department of Pediatrics, and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Wanda Phipatanakul
- Harvard Medical School, Boston, Mass; Division of Allergy and Immunology, Boston Children's Hospital, Boston, Mass
| | - Peggy S Lai
- Department of Internal Medicine, Massachusetts General Hospital, Boston, Mass; Harvard Medical School, Boston, Mass; Division of Allergy and Immunology, Boston Children's Hospital, Boston, Mass; Division of Pulmonary and Critical Care, Massachusetts General Hospital, Boston, Mass; Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Mass.
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13
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Affiliation(s)
- Ronald van Ree
- Departments of Experimental Immunology and of Otorhinolaryngology, Amsterdam University Medical Center, Location AMC, Amsterdam, Netherlands
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14
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Derqaoui S, Oukessou M, Attrassi K, Elftouhy FZ, Nassik S. Detection of Sutterella spp. in Broiler Liver and Breast. Front Vet Sci 2022; 9:859902. [PMID: 35433902 PMCID: PMC9009309 DOI: 10.3389/fvets.2022.859902] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 02/23/2022] [Indexed: 02/03/2023] Open
Abstract
Sutterella sp. is a gram-negative, microaerophilic bacterium that is particularly resistant to bile acids. It has recently been associated with several human pathologies such as inflammatory bowel disease, asthma, diabetes, and autism. Indeed, susceptibility patterns to ciprofloxacin and erythromycin, combined with resistance to metronidazole, indicate that Sutterella wadsworthensis patterns are closer to those of Campylobacter. The objective of this study is to identify, for the first time, Sutterella spp. in the liver and breast of broiler chickens by quantitative real-time PCR (qPCR). Liver, breast, and cecal content samples were taken from 25 birds and frozen at −20°C until analyzed. The main results showed that Sutterella sp. is part of the cecal microbiota of 48% of the birds and present in the liver and breast of, respectively 20 and 40% of the chicks with a variable Cq. We, therefore, conclude that Sutterella sp. exists in poultry and poultry meat and that foodstuffs of poultry origin might be considered as a potential source of contamination for humans.
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Affiliation(s)
- Sophia Derqaoui
- Unit of Avian Pathology, Department of Veterinary Pathology and Public Health, Agronomy and Veterinary Medicine Institute Hassan II, Rabat, Morocco
- *Correspondence: Sophia Derqaoui ; orcid.org/0000-0002-3355-2800
| | - Mohammed Oukessou
- Unit of Physiology and Therapeutics, Department of Veterinary Biological and Pharmaceutical Sciences, Agronomy and Veterinary Medicine Institute Hassan II, Rabat, Morocco
| | - Kawtar Attrassi
- Unit of Avian Pathology, Department of Veterinary Pathology and Public Health, Agronomy and Veterinary Medicine Institute Hassan II, Rabat, Morocco
| | - Fatima Zahra Elftouhy
- Unit of Avian Pathology, Department of Veterinary Pathology and Public Health, Agronomy and Veterinary Medicine Institute Hassan II, Rabat, Morocco
| | - Saadia Nassik
- Unit of Avian Pathology, Department of Veterinary Pathology and Public Health, Agronomy and Veterinary Medicine Institute Hassan II, Rabat, Morocco
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15
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Smeekens JM, Kulis MD. Mouse Models of Food Allergy in the Pursuit of Novel Treatment Modalities. FRONTIERS IN ALLERGY 2021; 2:810067. [PMID: 35387036 PMCID: PMC8974753 DOI: 10.3389/falgy.2021.810067] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 11/23/2021] [Indexed: 11/13/2022] Open
Abstract
The prevalence of IgE-mediated food allergies has increased dramatically in the past three decades, now affecting up to 10% of the US population. IgE-mediated food allergy is an immunologic disease, involving a variety of cells, including B and T cells, mast cells, basophils, ILC2s, and epithelial cells. Mouse models of food allergy mimic the overall immunologic processes known to exist in humans. Due to the limitations of invasive sampling of human tissue and the similarities of the human and mouse immune systems, comprehensive pathogenesis studies of food allergy have been performed in mouse models. Mouse models have been effective in elucidating the roles of non-oral routes of sensitization and identifying key cells and molecules involved in allergic sensitization. Furthermore, the development of novel therapeutic approaches for food allergy has been accelerated through the use of pre-clinical mouse models. Despite the groundbreaking findings stemming from research in mice, there are continued efforts to improve the translational utility of these models. Here, we highlight the achievements in understanding food allergy development and efforts to bring novel treatment approaches into clinical trials.
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Affiliation(s)
- Johanna M. Smeekens
- Division of Allergy and Immunology, Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC, United States
- University of North Carolina Food Allergy Initiative, Chapel Hill, NC, United States
- *Correspondence: Johanna M. Smeekens
| | - Michael D. Kulis
- Division of Allergy and Immunology, Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC, United States
- University of North Carolina Food Allergy Initiative, Chapel Hill, NC, United States
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16
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Vithoulkas G. An integrated perspective on transmutation of acute inflammation into chronic and the role of the microbiome. J Med Life 2021; 14:740-747. [PMID: 35126742 PMCID: PMC8811668 DOI: 10.25122/jml-2021-0375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 11/30/2021] [Indexed: 11/20/2022] Open
Abstract
The Continuum theory and the Levels of Health theory were separately proposed to explain the myriad responses to treatment and understand the process of health and disease in an individual. In light of accumulating evidence on the intricate relationship between the human immune system and microbiome, an attempt is made in this article to connect these two theories to explain the transmutation of the efficiently responding immune system (through the acute inflammatory response and high fever) to one involved in a low-grade chronic inflammatory process (resulting in chronic disease). There is already enough evidence to demonstrate the role of the microbiome in all chronic inflammatory diseases. In this article, we discuss the mechanism by which subjecting a healthy person to continuous drug treatment for acute inflammatory conditions (at a certain time) leads to transmutation to chronic disease. Although this hypothesis requires further experimental evidence, it calls for a reconsideration of the manner in which we treat acute infectious diseases in the population.
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Affiliation(s)
- George Vithoulkas
- University of the Aegean, Syros, Greece
- Postgraduate Doctors’ Training Institute, Health Care Ministry of the Chuvash Republic, Cheboksary, Russian Federation
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17
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Brown H, Esterházy D. Intestinal immune compartmentalization: implications of tissue specific determinants in health and disease. Mucosal Immunol 2021; 14:1259-1270. [PMID: 34211125 DOI: 10.1038/s41385-021-00420-8] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 05/05/2021] [Accepted: 05/24/2021] [Indexed: 02/04/2023]
Abstract
The emerging concept of tissue specific immunity has opened the gates to new inquiries into what factors drive immune cell niche adaptation and the implications on immune homeostasis, organ specific immune diseases, and therapeutic efficacy. These issues are particularly complicated at barrier sites, which are directly exposed to an ever-changing environment. In particular, the gastrointestinal (GI) tract faces even further challenges given the profound functional and structural differences along its length, raising the possibility that it may even have to be treated as multiple organs when seeking to answer these questions. In this review, we evaluate what is known about the tissue intrinsic and extrinsic factors shaping immune compartments in the intestine. We then discuss the physiological and pathological consequences of a regionally distinct immune system in a single organ, but also discuss where our insight into the role of the compartment for disease development is still very limited. Finally, we discuss the technological and therapeutic implications this compartmentalization has. While the gut is perhaps one of the most intensely studied systems, many of these aspects apply to understanding tissue specific immunity of other organs, most notably other barrier sites such as skin, lung, and the urogenital tract.
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Affiliation(s)
- Hailey Brown
- Committee on Immunology, University of Chicago, Chicago, IL, USA
| | - Daria Esterházy
- Committee on Immunology, University of Chicago, Chicago, IL, USA. .,Department of Pathology, University of Chicago, Chicago, IL, USA.
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18
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Haile AF, Woodfint RM, Kim E, Joldrichsen MR, Berhe N, Gebreyes WA, Boyaka PN. Broad-Spectrum and Gram-Negative-Targeting Antibiotics Differentially Regulate Antibody Isotype Responses to Injected Vaccines. Vaccines (Basel) 2021; 9:vaccines9111240. [PMID: 34835171 PMCID: PMC8619726 DOI: 10.3390/vaccines9111240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 10/11/2021] [Accepted: 10/14/2021] [Indexed: 11/19/2022] Open
Abstract
Antibiotics are extensively used worldwide for the treatment of common infections by agents such as E. coli and Salmonella. They also represent the most common cause of alteration of the microbiota in people. We addressed whether broad-spectrum and Gram-negative-targeting antibiotics differentially regulate systemic and mucosal immune responses to vaccines. Antibiotics treatment enhances serum IgG1 responses in mice immunized systemically with a model polyvalent vaccine. This increase was not seen for other IgG subclasses and was dependent on the immunogenicity of vaccine antigens. The broad-spectrum antibiotic cocktail also enhanced serum IgA responses. Interestingly, both the broad spectrum and the antibiotic targeting Gram-negative bacteria enhanced the number of IgA antibody secreting cells in the intestinal lamina propria. This effect was unlikely to be due to an increase in cells expressing gut-homing receptors (i.e., CCR9 and α4β7) in peripheral tissues. On the other hand, the microbiome in mice treated with antibiotics was characterized by an overall reduction of the number of firmicutes. Furthermore, Bacteroidetes were increased by either treatment, and Proteobacteria were increased by the broad-spectrum antibiotics cocktail. Thus, immunoglobulin isotype and subclass responses are differentially regulated by oral antibiotics treatment and the gut microbiota shapes mucosal antibody responses after systemic immunization.
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Affiliation(s)
- Aklilu F. Haile
- Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA; (A.F.H.); (R.M.W.); (E.K.); (M.R.J.)
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa 1000, Ethiopia;
| | - Rachel M. Woodfint
- Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA; (A.F.H.); (R.M.W.); (E.K.); (M.R.J.)
| | - Eunsoo Kim
- Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA; (A.F.H.); (R.M.W.); (E.K.); (M.R.J.)
| | - Marisa R. Joldrichsen
- Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA; (A.F.H.); (R.M.W.); (E.K.); (M.R.J.)
| | - Nega Berhe
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa 1000, Ethiopia;
| | - Wondwoossen A. Gebreyes
- Department of Preventive Medicine, The Ohio State University, Columbus, OH 43210, USA;
- Global One Health Initiative, The Ohio State University, Columbus, OH 43210, USA
- Infection Diseases Institute, The Ohio State University, Columbus, OH 43210, USA
| | - Prosper N. Boyaka
- Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA; (A.F.H.); (R.M.W.); (E.K.); (M.R.J.)
- Global One Health Initiative, The Ohio State University, Columbus, OH 43210, USA
- Infection Diseases Institute, The Ohio State University, Columbus, OH 43210, USA
- Department Microbial Immunity and Infection, The Ohio State University, Columbus, OH 43210, USA
- Correspondence:
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19
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Wang M, Yu M, Kong WJ, Cui M, Gao F. Association between intestinal neoplasms and celiac disease: A review. World J Gastrointest Oncol 2021; 13:1017-1028. [PMID: 34616509 PMCID: PMC8465454 DOI: 10.4251/wjgo.v13.i9.1017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 06/02/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is a chronic immune-mediated intestinal disease with genetic susceptibility. It is characterized by inflammatory damage to the small intestine after ingestion of cereals and products containing gluten protein. In recent years, the global prevalence rate of CD has been approximately 1%, and is gradually increasing. CD patients adhere to a gluten-free diet (GFD) throughout their entire life. However, it is difficult to adhere strictly to a GFD. Untreated CD may be accompanied by gastrointestinal symptoms, such as diarrhea, abdominal pain, and extraintestinal symptoms caused by secondary malnutrition. Many studies have suggested that CD is associated with intestinal tumors such as enteropathy-associated T-cell lymphoma (EATL), small bowel cancer (SBC), and colorectal cancer. In this study, we reviewed related studies published in the literature to provide a reference for the prevention and treatment of intestinal tumors in patients with CD. Compared with the general population, CD patients had a high total risk of SBC and EATL, but not colorectal cancer. The protective effect of GFD on CD-related malignancies is controversial. Further studies are needed to confirm whether GFD treatment can reduce the risk of intestinal neoplasms in CD.
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Affiliation(s)
- Man Wang
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Ming Yu
- Department of General Practice, Xiangyang Central Hospital, The Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021 Hubei Province, China
| | - Wen-Jie Kong
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Mei Cui
- Department of Pathology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Feng Gao
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
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20
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Smith NA, Germundson DL, Gao P, Hur J, Floden AM, Nagamoto-Combs K. Anxiety-like behavior and intestinal microbiota changes as strain-and sex-dependent sequelae of mild food allergy in mouse models of cow's milk allergy. Brain Behav Immun 2021; 95:122-141. [PMID: 33705867 PMCID: PMC8525516 DOI: 10.1016/j.bbi.2021.03.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 02/20/2021] [Accepted: 03/02/2021] [Indexed: 12/12/2022] Open
Abstract
A number of studies have reported comorbidity of food allergies with various neuropsychiatric disorders, such as anxiety, depression, attention-deficit hyperactivity disorder, and autism. However, inconsistent results across clinical studies have left the association between food allergy and behavioral disorders inconclusive. We postulated that the heterogeneities in genetic background among allergic cohorts affect symptom presentation and severity of food allergy, introducing bias in patient selection criteria toward individuals with overt physical reactions. To understand the influence of genetic background on food allergy symptoms and behavioral changes beyond anaphylaxis, we generated mouse models with mild cow's milk allergy by sensitizing male and female C57BL/6J and BALB/cJ mice to a bovine whey protein, β-lactoglobulin (BLG; Bos d 5). We compared strain- and sex-dependent differences in their immediate physical reactions to BLG challenge as well as anxiety-like behavior one day after the challenge. While reactions to the allergen challenge were either absent or mild for all groups, a greater number of BLG-sensitized BALB/cJ mice presented visible symptoms and hypothermia compared to C57BL/6J mice. Interestingly, male mice of both strains displayed anxiety-like behavior on an elevated zero maze without exhibiting cognitive impairment with the cross maze test. Further characterization of plasma cytokines/chemokines and fecal microbiota also differentiated strain- and sex-dependent effects of BLG sensitization on immune-mediator levels and bacterial populations, respectively. These results demonstrated that the genetic variables in mouse models of milk allergy influenced immediate physical reactions to the allergen, manifestation of anxiety-like behavior, levels of immune responses, and population shift in gut microbiota. Thus, stratification of allergic cohorts by their symptom presentations and severity may strengthen the link between food allergy and behavioral disorders and identify a population(s) with specific genetic background that have increased susceptibility to allergy-associated behavioral disorders.
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Affiliation(s)
- Nicholas A Smith
- Department of Pathology, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA.
| | - Danielle L Germundson
- Department of Pathology, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA.
| | - Pan Gao
- Department of Biomedical Sciences, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA.
| | - Junguk Hur
- Department of Biomedical Sciences, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA.
| | - Angela M Floden
- Department of Biomedical Sciences, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA.
| | - Kumi Nagamoto-Combs
- Department of Biomedical Sciences, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA.
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21
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Olshan KL, Zomorrodi AR, Pujolassos M, Troisi J, Khan N, Fanelli B, Kenyon V, Fasano A, Leonard MM. Microbiota and Metabolomic Patterns in the Breast Milk of Subjects with Celiac Disease on a Gluten-Free Diet. Nutrients 2021; 13:nu13072243. [PMID: 34210038 PMCID: PMC8308312 DOI: 10.3390/nu13072243] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 06/14/2021] [Accepted: 06/25/2021] [Indexed: 12/30/2022] Open
Abstract
The intestinal microbiome may trigger celiac disease (CD) in individuals with a genetic disposition when exposed to dietary gluten. Research demonstrates that nutrition during infancy is crucial to the intestinal microbiome engraftment. Very few studies to date have focused on the breast milk composition of subjects with a history of CD on a gluten-free diet. Here, we utilize a multi-omics approach with shotgun metagenomics to analyze the breast milk microbiome integrated with metabolome profiling of 36 subjects, 20 with CD on a gluten-free diet and 16 healthy controls. These analyses identified significant differences in bacterial and viral species/strains and functional pathways but no difference in metabolite abundance. Specifically, three bacterial strains with increased abundance were identified in subjects with CD on a gluten-free diet of which one (Rothia mucilaginosa) has been previously linked to autoimmune conditions. We also identified five pathways with increased abundance in subjects with CD on a gluten-free diet. We additionally found four bacterial and two viral species/strains with increased abundance in healthy controls. Overall, the differences observed in bacterial and viral species/strains and in functional pathways observed in our analysis may influence microbiome engraftment in neonates, which may impact their future clinical outcomes.
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Affiliation(s)
- Katherine L. Olshan
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA; (K.L.O.); (A.R.Z.); (A.F.)
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Boston, MA 02129, USA;
- Department of Pediatrics, Harvard Medical School, Harvard University, Boston, MA 02115, USA
- Celiac Research Program, Harvard Medical School, Boston, MA 02115, USA
| | - Ali R. Zomorrodi
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA; (K.L.O.); (A.R.Z.); (A.F.)
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Boston, MA 02129, USA;
- Department of Pediatrics, Harvard Medical School, Harvard University, Boston, MA 02115, USA
- Celiac Research Program, Harvard Medical School, Boston, MA 02115, USA
| | | | - Jacopo Troisi
- Theoreo srl, University of Salerno, 84084 Salerno, Italy; (M.P.); (J.T.)
- Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, 84084 Salerno, Italy
- European Biomedical Research Institute of Salerno (EBRIS), Via S. De Renzi, 50, 84125 Salerno, Italy
| | - Nayeim Khan
- CosmosID Inc., Rockville, MD 20850, USA; (N.K.); (B.F.)
| | - Brian Fanelli
- CosmosID Inc., Rockville, MD 20850, USA; (N.K.); (B.F.)
| | - Victoria Kenyon
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Boston, MA 02129, USA;
- Celiac Research Program, Harvard Medical School, Boston, MA 02115, USA
| | - Alessio Fasano
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA; (K.L.O.); (A.R.Z.); (A.F.)
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Boston, MA 02129, USA;
- Department of Pediatrics, Harvard Medical School, Harvard University, Boston, MA 02115, USA
- Celiac Research Program, Harvard Medical School, Boston, MA 02115, USA
- Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, 84084 Salerno, Italy
| | - Maureen M. Leonard
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA; (K.L.O.); (A.R.Z.); (A.F.)
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Boston, MA 02129, USA;
- Department of Pediatrics, Harvard Medical School, Harvard University, Boston, MA 02115, USA
- Celiac Research Program, Harvard Medical School, Boston, MA 02115, USA
- Correspondence:
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22
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Pi X, Yang Y, Sun Y, Cui Q, Wan Y, Fu G, Chen H, Cheng J. Recent advances in alleviating food allergenicity through fermentation. Crit Rev Food Sci Nutr 2021; 62:7255-7268. [PMID: 33951963 DOI: 10.1080/10408398.2021.1913093] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
The increasing prevalence of food allergies is a significant challenge to global food health and safety. Various strategies have been deployed to decrease the allergenicity of food for preventing and reducing related disorders. Compared to other methods, fermentation has unique advantages in reducing the allergenicity of food and may represent a new trend in preventing food-induced allergies. This review introduces the characteristics of allergens in various foods, including shellfish, soy, peanut, milk, tree nut, egg, wheat, and fish. The mechanism and pathological symptoms of allergic reactions are then summarized. Furthermore, the advantages of fermentation for reducing the allergenicity of these foods and preventing allergies are evaluated. Fermentation is an efficient approach for reducing or eliminating food allergenicity. Simultaneously, it improved the nutritional value and physicochemical properties of food materials. It is conceivable that a combination of mixed strain fermentation with additional processing, such as heat treatment, pulsed light, and ultrasonication, will efficiently reduce the allergenicity of various foods and preserve their unique taste and nutritional components, providing significance for patients with allergies.
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Affiliation(s)
- Xiaowen Pi
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang, China
| | - Yili Yang
- Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, Jiangsu, China
| | - Yuxue Sun
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang, China
| | - Qiang Cui
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang, China
| | - Yin Wan
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China
| | - Guiming Fu
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China
| | - Hongbing Chen
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China
| | - Jianjun Cheng
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang, China
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23
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Nedelkopoulou N, Taparkou A, Raftopoulou S, Gidaris D, Xinias I, Mavroudi A, Dhawan A, Farmaki E. Association of IL-10 gene promoter polymorphisms with food allergy susceptibility and serum IL-10 level in a pediatric Caucasian population. Pediatr Allergy Immunol 2021; 32:552-559. [PMID: 33179333 DOI: 10.1111/pai.13407] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 10/29/2020] [Accepted: 11/02/2020] [Indexed: 11/26/2022]
Abstract
BACKGROUND Interleukin 10 has been shown to play a critical role in the regulation of the immune responses in allergic diseases. AIM To investigate if genetic polymorphisms in the promoter region of the IL-10 gene are associated with food allergy (FA) susceptibility in Caucasian pediatric patients with concomitant allergic diseases and IL-10 levels. METHODS The single nucleotide polymorphisms (SNPs) at -1082A > G (rs1800896), -819 T > C (rs1800871), and -592A > C (rs1800872) of 62 pediatric patients with IgE-mediated FA were analyzed and correlated with clinical parameters, serum IgE and IL-10 levels. The results were compared with those of 92 healthy controls without FA, personal and/or family history of atopy. RESULTS Analysis and comparison of genotype distributions, allele frequencies, and haplotypes showed that none of the genotypes confers an increased risk of FA. The genotype -1082 AA in FA patients was associated with moderate to severe symptoms of FA, the development of atopic asthma, and higher levels of IL-10. In a linear regression study, we confirmed that the genotype -1082 AA acts as an independent factor for the higher levels of IL-10. A positive association was also observed between -819T/C and -592 A/C SNPs and later onset of FA. CONCLUSION Polymorphisms in the promoter region of the IL-10 gene are not associated with FA susceptibility in our cohort. In FA patients, -1082 A/G SNPs seem to influence the production of IL-10, the severity of FA symptoms, and the development of atopic asthma in this population.
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Affiliation(s)
- Natalia Nedelkopoulou
- 1st Department of Paediatrics, Paediatric Immunology and Rheumatology Referral Centre, Hippokration General Hospital, Aristotle University, Thessaloniki, Greece.,Pediatric Gastroenterology Department, Sheffield Children's Hospital Foundation Trust, Sheffield, UK
| | - Anna Taparkou
- 1st Department of Paediatrics, Paediatric Immunology and Rheumatology Referral Centre, Hippokration General Hospital, Aristotle University, Thessaloniki, Greece
| | - Sofia Raftopoulou
- Laboratory of Immunology and Histocompatibility, Department of Medicine, University of Thessaly, Larisa, Greece
| | - Dimos Gidaris
- 1st Department of Paediatrics, Hippokration General Hospital, Aristotle University, Thessaloniki, Greece.,University of Nicosia, Nicosia, Cyprus
| | - Ioannis Xinias
- 3rd Department of Paediatrics, Hippokration General Hospital, Aristotle University, Thessaloniki, Greece
| | - Antigoni Mavroudi
- 3rd Department of Paediatrics, Hippokration General Hospital, Aristotle University, Thessaloniki, Greece
| | - Anil Dhawan
- Pediatric Liver, GI and Nutrition Centre, King's College Hospital and MowatLabs, London, UK
| | - Evangelia Farmaki
- 1st Department of Paediatrics, Paediatric Immunology and Rheumatology Referral Centre, Hippokration General Hospital, Aristotle University, Thessaloniki, Greece
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24
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D'Avino P, Serena G, Kenyon V, Fasano A. An updated overview on celiac disease: from immuno-pathogenesis and immuno-genetics to therapeutic implications. Expert Rev Clin Immunol 2021; 17:269-284. [PMID: 33472447 DOI: 10.1080/1744666x.2021.1880320] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Celiac disease (CD) is an autoimmune enteropathy triggered by ingestion of gluten. While presenting many similarities with other autoimmune diseases, celiac disease is unique in that the external trigger, gluten, and the genetic background necessary for disease development (HLA DQ2/DQ8) are well described. The prevalence of celiac disease is dramatically increasing over the years and new epidemiologic data show changes regarding age of onset and symptoms. A better understanding of CD-pathogenesis is fundamental to highlight the reasons of this rise of celiac diagnoses. AREAS COVERED In this review we describe CD-pathogenesis by dissecting all the components necessary to lose tolerance to gluten (ingestion of gluten, genetic predisposition, loss of barrier function and immune response). Additionally, we also highlight the role that microbiome plays in celiac disease as well as new proposed therapies and experimental tools. EXPERT OPINION Prevalence of autoimmune diseases is increasing around the world. As a result, modern society is strongly impacted by a social and economic burden. Given the unique characteristics of celiac disease, a better understanding of its pathogenesis and the factors that contribute to it may shed light on other autoimmune diseases for which external trigger and genetic background are not known.
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Affiliation(s)
- Paolo D'Avino
- Division of Pediatric Gastroenterology and Nutrition, Mass General Hospital for Children, Harvard Medical School, Boston, MA, USA.,Mucosal Immunology and Biology Research Center, Mass General Hospital for Children, Harvard Medical School, Boston, MA, USA.,Celiac Research Program, Harvard Medical School, Boston, MA, USA.,Vita-Salute San Raffaele University, Milan, Italy
| | - Gloria Serena
- Division of Pediatric Gastroenterology and Nutrition, Mass General Hospital for Children, Harvard Medical School, Boston, MA, USA.,Mucosal Immunology and Biology Research Center, Mass General Hospital for Children, Harvard Medical School, Boston, MA, USA.,Celiac Research Program, Harvard Medical School, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA
| | - Victoria Kenyon
- Division of Pediatric Gastroenterology and Nutrition, Mass General Hospital for Children, Harvard Medical School, Boston, MA, USA.,Mucosal Immunology and Biology Research Center, Mass General Hospital for Children, Harvard Medical School, Boston, MA, USA.,Celiac Research Program, Harvard Medical School, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA
| | - Alessio Fasano
- Division of Pediatric Gastroenterology and Nutrition, Mass General Hospital for Children, Harvard Medical School, Boston, MA, USA.,Mucosal Immunology and Biology Research Center, Mass General Hospital for Children, Harvard Medical School, Boston, MA, USA.,Celiac Research Program, Harvard Medical School, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA.,European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy
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25
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Kakiuchi T, Yamamoto K, Imamura I, Hashiguchi K, Kawakubo H, Yamaguchi D, Fujioka Y, Okuda M. Gut microbiota changes related to Helicobacter pylori eradication with vonoprazan containing triple therapy among adolescents: a prospective multicenter study. Sci Rep 2021; 11:755. [PMID: 33436953 PMCID: PMC7804423 DOI: 10.1038/s41598-020-80802-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 12/29/2020] [Indexed: 12/14/2022] Open
Abstract
Currently, it is unclear whether treating Helicobacter pylori (H. pylori) infection is safe among adolescents. This study aimed to evaluate the safety of H. pylori eradication therapy by examining gut microbiota changes in adolescents 3 months after the therapy. H. pylori-infected adolescents were enrolled in this study. Their stool samples were collected at the following three time points: before treatment, 1-2 days after completion of treatment, and time of eradication successful judgment. We assessed the relative abundance, alpha-diversity, and beta-diversity of the gut microbiota and adverse events. The number of isolated Actinobacteria decreased immediately after eradication therapy in the 16 students included in the study, and it returned to pretreatment condition at the eradication judgment point. There was no change in the relative abundance at genus level. The alpha-diversity was lost immediately after eradication therapy; however, it recovered at the time of eradication judgment, and it was restored to pretreatment condition. Meanwhile, none of the participants experienced serious adverse events. H. pylori eradication therapy is safe for adolescents with respect to gut microbiota changes associated with H. pylori eradication therapy. Therefore, further long-term evaluations of gut microbiota changes following eradication therapy are warranted.
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Affiliation(s)
- Toshihiko Kakiuchi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan.
| | - Kentaroh Yamamoto
- Department of Gastroenterology, Yamamoto Memorial Hospital, Imari, Japan
| | - Ichiro Imamura
- Department of Gastroenterology, Imamura Hospital, Tosu, Japan
| | | | - Hiroharu Kawakubo
- Department of Gastroenterology, ImariArita Kyoritsu Hospital, Nishimatsuura, Japan
| | - Daisuke Yamaguchi
- Department of Gastroenterology, Ureshino Medical Center, Ureshino, Japan
| | | | - Masumi Okuda
- Department of Pediatrics, Hyogo College of Medicine, Nishinomiya, Japan
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26
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Benedé S, Berin MC. Applications of Mouse Models to the Study of Food Allergy. Methods Mol Biol 2021; 2223:1-17. [PMID: 33226583 DOI: 10.1007/978-1-0716-1001-5_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Mouse models of allergic disease offer numerous advantages when compared to the models of other animals. However, selection of appropriate mouse models is critical to advance the field of food allergy by revealing mechanisms of allergy and for testing novel therapeutic approaches. All current mouse models for food allergy have weaknesses that may limit their applicability to human disease. Aspects such as the genetic predisposition to allergy or tolerance from the strain of mouse used, allergen dose, route of exposure (oral, intranasal, intraperitoneal, or epicutaneous), damage of the epithelial barrier, use of adjuvants, food matrix effects, or composition of the microbiota should be considered prior to the selection of a specific murine model and contemplated according to the intended purpose of the study. This chapter reviews our current knowledge on the application of mouse models to food allergy research and the variables that may influence the successful development of each type of model.
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Affiliation(s)
- Sara Benedé
- Instituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC-UAM, Madrid, Spain
- Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - M Cecilia Berin
- Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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27
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Olshan KL, Leonard MM, Serena G, Zomorrodi AR, Fasano A. Gut microbiota in Celiac Disease: microbes, metabolites, pathways and therapeutics. Expert Rev Clin Immunol 2020; 16:1075-1092. [PMID: 33103934 DOI: 10.1080/1744666x.2021.1840354] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Current evidence supports a vital role of the microbiota on health outcomes, with alterations in an otherwise healthy balance linked to chronic medical conditions like celiac disease (CD). Recent advances in microbiome analysis allow for unparalleled profiling of the microbes and metabolites. With the growing volume of data available, trends are emerging that support a role for the gut microbiota in CD pathogenesis. AREAS COVERED In this article, the authors review the relationship between factors such as genes and antibiotic exposure on CD onset and the intestinal microbiota. The authors also review other microbiota within the human body (like the oropharynx) that may play a role in CD pathogenesis. Finally, the authors discuss implications for disease modification and the ultimate goal of prevention. The authors reviewed literature from PubMed, EMBASE, and Web of Science. EXPERT OPINION CD serves as a unique opportunity to explore the role of the intestinal microbiota on the development of chronic autoimmune disease. While research to date provides a solid foundation, most studies have been case-control and thus do not have capacity to explore the mechanistic role of the microbiota in CD onset. Further longitudinal studies and integrated multi-omics are necessary for investigating CD pathogenesis.
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Affiliation(s)
- Katherine L Olshan
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Celiac Research Program, Harvard Medical School , Boston, MA, USA
| | - Maureen M Leonard
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Celiac Research Program, Harvard Medical School , Boston, MA, USA
| | - Gloria Serena
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Celiac Research Program, Harvard Medical School , Boston, MA, USA
| | - Ali R Zomorrodi
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Celiac Research Program, Harvard Medical School , Boston, MA, USA
| | - Alessio Fasano
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,European Biomedical Research Institute of Salerno (EBRIS) , Salerno, Italy
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28
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Altered vaginal microbiome and relative co-abundance network in pregnant women with penicillin allergy. Allergy Asthma Clin Immunol 2020; 16:79. [PMID: 32944033 PMCID: PMC7491301 DOI: 10.1186/s13223-020-00475-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 08/27/2020] [Indexed: 12/31/2022] Open
Abstract
Background Penicillin allergy is frequently reported in adults and children. Recent studies suggest that microbiota plays a key role in the development and progression of allergy. In this study, the relationship between vaginal microbiome and pregnant women with penicillin allergy was investigated. Methods Vaginal samples before labor from 12 pregnant women with penicillin allergy and 15 non-allergic pregnant women were collected. Bacterial community structure of all study subjects and the discrepancies between the two groups were analyzed using 16S rRNA sequencing based on Illumina Hiseq 2500 platform. Results The abundant phyla among all participants were Firmicutes, Actinobacteria and Bacteroidetes. The predominant genus was Lactobacillus. Compared to non-allergic pregnant women, Actinobacteria, Coriobacteriaceae, Lachnospiraceae, Paraprevotella and Anoxybacillus significantly decreased, whereas Deltaproteobacteria, Peptostreptococcaceae, Enterococcus and Megamonas were more abundant in penicillin allergic women. Additionally, obvious discrepancies were observed in the co-abundance network at the genus level between the two groups. Conclusions There were differences in the microbial community structure and composition of reproduction tract between penicillin allergic and non-allergic pregnant women. These shifts may be related to maternal and neonatal health.
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29
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Microbiome of root vegetables-a source of gluten-degrading bacteria. Appl Microbiol Biotechnol 2020; 104:8871-8885. [PMID: 32875365 PMCID: PMC7502452 DOI: 10.1007/s00253-020-10852-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 07/29/2020] [Accepted: 08/23/2020] [Indexed: 12/11/2022]
Abstract
Abstract Gluten is a cereal protein that is incompletely digested by human proteolytic enzymes that create immunogenic peptides that accumulate in the gastrointestinal tract (GIT). Although both environmental and human bacteria have been shown to expedite gluten hydrolysis, gluten intolerance is a growing concern. Here we hypothesize that together with food, we acquire environmental bacteria that could impact our GIT with gluten-degrading bacteria. Using in vitro gastrointestinal simulation conditions, we evaluated the capacity of endophytic bacteria that inhabit root vegetables, potato (Solanum tuberosum), carrot (Daucus sativus), beet (Beta vulgaris), and topinambur (Jerusalem artichoke) (Helianthus tuberosus), to resist these conditions and degrade gluten. By 16S rDNA sequencing, we discovered that bacteria from the families Enterobacteriaceae, Bacillaceae, and Clostridiaceae most effectively multiply in conditions similar to the human GIT (microoxic conditions, 37 °C) while utilizing vegetable material and gluten as nutrients. Additionally, we used stomach simulation (1 h, pH 3) and intestinal simulation (1 h, bile salts 0.4%) treatments. The bacteria that survived this treatment retained the ability to degrade gluten epitopes but at lower levels. Four bacterial strains belonging to species Bacillus pumilus, Clostridium subterminale, and Clostridium sporogenes isolated from vegetable roots produced proteases with postproline cleaving activity that successfully neutralized the toxic immunogenic epitopes. Key points • Bacteria from root vegetables can degrade gluten. • Some of these bacteria can resist conditions mimicking gastrointestinal tract. Electronic supplementary material The online version of this article (10.1007/s00253-020-10852-0) contains supplementary material, which is available to authorized users.
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30
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Di Costanzo M, Carucci L, Berni Canani R, Biasucci G. Gut Microbiome Modulation for Preventing and Treating Pediatric Food Allergies. Int J Mol Sci 2020; 21:ijms21155275. [PMID: 32722378 PMCID: PMC7432728 DOI: 10.3390/ijms21155275] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 07/22/2020] [Accepted: 07/23/2020] [Indexed: 12/11/2022] Open
Abstract
The increasing prevalence and severity of pediatric food allergies (FA) demands innovative preventive and therapeutic strategies. Emerging evidence suggests a pivotal role for the gut microbiome in modulating susceptibility to FA. Studies have demonstrated that alteration of gut microbiome could precede FA, and that particular microbial community structures early in life could influence also the disease course. The identification of gut microbiome features in pediatric FA patients is driving new prevention and treatment approaches. This review is focused on the potential role of the gut microbiome as a target for FA prevention and treatment.
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Affiliation(s)
- Margherita Di Costanzo
- Department of Pediatrics and Neonatology, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy;
- Department of Translational Medical Science-Pediatric Section, University “Federico II”, 80131 Naples, Italy; (L.C.); (R.B.C.)
- ImmunoNutritionLab-CEINGE Advanced Biotechnologies, University “Federico II”, 80131 Naples, Italy
- Correspondence:
| | - Laura Carucci
- Department of Translational Medical Science-Pediatric Section, University “Federico II”, 80131 Naples, Italy; (L.C.); (R.B.C.)
- ImmunoNutritionLab-CEINGE Advanced Biotechnologies, University “Federico II”, 80131 Naples, Italy
| | - Roberto Berni Canani
- Department of Translational Medical Science-Pediatric Section, University “Federico II”, 80131 Naples, Italy; (L.C.); (R.B.C.)
- ImmunoNutritionLab-CEINGE Advanced Biotechnologies, University “Federico II”, 80131 Naples, Italy
- Task Force on Microbiome Studies, University of Naples “Federico II”, 80131 Naples, Italy
- European Laboratory for the Investigation of Food-Induced Diseases, University of Naples “Federico II”, 80131 Naples, Italy
| | - Giacomo Biasucci
- Department of Pediatrics and Neonatology, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy;
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31
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Huang CH, Lu SY, Tsai WC. Relevant fecal microbes isolated from mice with food allergy elicited intestinal cytokine/chemokine network and T-cell immune responses. BIOSCIENCE OF MICROBIOTA FOOD AND HEALTH 2020; 39:234-242. [PMID: 33117622 PMCID: PMC7573112 DOI: 10.12938/bmfh.2020-014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 06/11/2020] [Indexed: 12/12/2022]
Abstract
The objective of this study was to identify the relevant fecal microbes from mice with
food allergy and investigate the impact of these microbes on intestinal epithelial cells
and allergen-specific T-cell responses. A murine model of ovalbumin (OVA)-induced food
allergy was employed. The profile of fecal microbiota was evaluated by the traditional
plating method and next-generation sequencing (NGS) of the 16S ribosomal RNA gene. The
density of fecal bacteria growth on RCM, TSA and LB plates was elevated in mice with food
allergy, whereas the diversity of fecal bacteria was decreased. Additionally, the relative
abundances of Prevotellaceae and Prevotella were increased. The isolated
fecal strains, mostly belonging to Enterococcus, Streptococcus and
Vagococcus, significantly reduced the viability of intestinal Caco-2
cells but increased the production of interleukin (IL)-8, C-C motif chemokine ligand
(CCL)-2, CCL-5, CCL-20 and C-X-C motif chemokine ligand (CXCL)-1. Moreover, cell expansion
and secretion of IL-2, interferon (IFN)-γ, IL-4 and IL-17 by mesenteric lymph node (MLN)
cells were augmented, whereas the production of IL-10 and transforming growth factor
(TGF)-β was diminished. Although individual fecal strains had varying degrees of impact on
Caco-2 cells and MLN cells, these results precisely indicate a different profile of fecal
microbiota between normal mice and allergic mice. Most important, the relevant fecal
microbes involved in allergen-induced dysbiosis have the potential to induce intestinal
cytokine/chemokine network and T-cell immune responses.
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Affiliation(s)
- Chung-Hsiung Huang
- Department of Food Science, National Taiwan Ocean University, 2 Pei-Ning Road, Keelung 20224, Taiwan, ROC
| | - Shueh-Yu Lu
- Department of Food Science, National Taiwan Ocean University, 2 Pei-Ning Road, Keelung 20224, Taiwan, ROC
| | - Wei-Chung Tsai
- Department of Food Science, National Taiwan Ocean University, 2 Pei-Ning Road, Keelung 20224, Taiwan, ROC
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32
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Ray C, Ming X. Climate Change and Human Health: A Review of Allergies, Autoimmunity and the Microbiome. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17134814. [PMID: 32635435 PMCID: PMC7369820 DOI: 10.3390/ijerph17134814] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 06/26/2020] [Accepted: 06/29/2020] [Indexed: 12/24/2022]
Abstract
The impact of climate change on human health is a topic of critical importance. While only recently beginning to gain attention, it is clear that immediate action is necessary to minimize this impact. In our review, we will outline a subset of these effects in detail. We will examine how climate change has worsened respiratory allergic disease. We will discuss how climate change has altered antigen exposure, possibly disrupting antigen-specific tolerance by the immune system, leading, in turn, to an increase in the prevalence of immunologic diseases. Finally, we will explore how the loss of biodiversity related to climate change may affect the microbiome, potentially leading to dysbiosis, inflammatory, autoimmune and neurologic diseases.
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Affiliation(s)
| | - Xue Ming
- Correspondence: ; Tel.: +1-973-972-2922
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33
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Gut microbiome alterations in patients with wheat-dependent exercise-induced anaphylaxis. Int Immunopharmacol 2020; 84:106557. [PMID: 32388491 DOI: 10.1016/j.intimp.2020.106557] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 04/25/2020] [Accepted: 04/30/2020] [Indexed: 01/23/2023]
Abstract
The intestinal microbiota plays a critical role in food allergy development. However, little is known regarding the structure and composition of the intestinal microbiota in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA). We examined the gut microbiota alterations in patients with WDEIA and the microbiota's association with WDEIA. Fecal samples were collected from 25 patients with WDEIA and 25 healthy controls. Environmental exposure factors were obtained, serum total IgE, IgE specific to wheat, gluten, and ω-5 gliadin were measured. Fecal samples were profiled using 16S rRNA gene sequencing. The relative abundances of the bacterial genera Blautia (P < 0.05), Erysipelatoclostridium (P < 0.01), Akkermansia (P < 0.05) and Lachnospiraceae_NK4A136_group (P < 0.05) were significantly increased, while those of Lactobacillus (P = 0.001) and Dialister (P < 0.05) were significantly decreased in subjects with WDEIA. The microbial diversity did not differ between WDEIA patients and healthy controls. IgE specific to ω-5 gliadin was positively associated with the Oscillospira (r = 0.48, P < 0.05) and negatively associated with Leuconostoc (r = -0.49, P < 0.05). Total IgE levels were significantly negatively correlated with Bifidobacterium (P < 0.05). The gut microbiome compositions in WDEIA patients differed from those of healthy controls. We identified a potential association between the gut microbiome and WDEIA development. Our findings may suggest new methods for preventing and treating WDEIA.
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34
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De Martinis M, Sirufo MM, Viscido A, Ginaldi L. Food Allergy Insights: A Changing Landscape. Arch Immunol Ther Exp (Warsz) 2020; 68:8. [PMID: 32239297 DOI: 10.1007/s00005-020-00574-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 02/27/2020] [Indexed: 12/15/2022]
Abstract
The panorama of food allergies (FA) has changed profoundly in recent years. In light of recent advances in knowledge of pathogenetic mechanisms and a greater attention to the multifaceted range of possible clinical manifestations, there is a need for a critical review of past classifications. Changes in nutrition, environment and lifestyles around the world are modifying the global FA epidemiology and new FA phenotypes are also emerging. Furthermore, both biotechnological advances in this field and recent personalized therapies have improved the diagnostic and therapeutic approach to FA. Consequently, both the prevention and clinical management of FA are rapidly changing and new therapeutic strategies are emerging, even revolutionizing the current medical practice. Given the significant increase in the prevalence of FA in recent years, the objective of this review is to provide an updated and complete overview of current knowledge in its etiopathogenesis, diagnostics and therapy, useful not only for a better understanding of this frequent and complex pathology but also for practical guidance in its clinical management.
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Affiliation(s)
- Massimo De Martinis
- Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy. .,Allergy and Clinical Immunology Unit, AUSL 04, Teramo, Italy.
| | - Maria Maddalena Sirufo
- Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.,Allergy and Clinical Immunology Unit, AUSL 04, Teramo, Italy
| | - Angelo Viscido
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Lia Ginaldi
- Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.,Allergy and Clinical Immunology Unit, AUSL 04, Teramo, Italy
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35
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De Martinis M, Sirufo MM, Suppa M, Ginaldi L. New Perspectives in Food Allergy. Int J Mol Sci 2020; 21:E1474. [PMID: 32098244 PMCID: PMC7073187 DOI: 10.3390/ijms21041474] [Citation(s) in RCA: 117] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 02/11/2020] [Accepted: 02/19/2020] [Indexed: 12/13/2022] Open
Abstract
The improvement of the knowledge of the pathophysiological mechanisms underlying the tolerance and sensitization to food antigens has recently led to a radical change in the clinical approach to food allergies. Epidemiological studies show a global increase in the prevalence of food allergy all over the world and manifestations of food allergy appear increasingly frequent also in elderly subjects. Environmental and nutritional changes have partly changed the epidemiology of allergic reactions to foods and new food allergic syndromes have emerged in recent years. The deepening of the study of the intestinal microbiota has highlighted important mechanisms of immunological adaptation of the mucosal immune system to food antigens, leading to a revolution in the concept of immunological tolerance. As a consequence, new prevention models and innovative therapeutic strategies aimed at a personalized approach to the patient affected by food allergy are emerging. This review focuses on these new perspectives and their practical implications in the management of food allergy, providing an updated view of this complex pathology.
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Affiliation(s)
- Massimo De Martinis
- Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (M.M.S.); (L.G.)
- Allergy and Clinical Immunology Unit, Center for the diagnosis and treatment of Osteoporosis, AUSL 04 Teramo, Italy
| | - Maria Maddalena Sirufo
- Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (M.M.S.); (L.G.)
- Allergy and Clinical Immunology Unit, Center for the diagnosis and treatment of Osteoporosis, AUSL 04 Teramo, Italy
| | - Mariano Suppa
- Department of Dermatology, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium;
| | - Lia Ginaldi
- Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (M.M.S.); (L.G.)
- Allergy and Clinical Immunology Unit, Center for the diagnosis and treatment of Osteoporosis, AUSL 04 Teramo, Italy
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36
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Dong X, Wang J, Raghavan V. Critical reviews and recent advances of novel non-thermal processing techniques on the modification of food allergens. Crit Rev Food Sci Nutr 2020; 61:196-210. [PMID: 32048519 DOI: 10.1080/10408398.2020.1722942] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Nowadays, the increasing prevalence of food allergy has become a public concern related to human health worldwide. Thus, it is imperative and necessary to provide some efficient methods for the management of food allergy. Some conventional processing methods (e.g., boiling and steaming) have been applied in the reduction of food immunoreactivity, while these treatments significantly destroy nutritional components present in food sources. Several studies have shown that novel processing techniques generally have better performance in retaining original characteristics of food and improving the efficiency of eliminating allergens. This review has focused on the recent advances of novel non-thermal processing techniques including high-pressure processing, ultrasound, pulsed light, cold plasma, fermentation, pulsed electric field, enzymatic hydrolysis, and the combination processing of them. Meanwhile, general information on global food allergy prevalence and food allergy pathology are also described. Hopefully, these findings regarding the modifications on the food allergens through various novel food processing techniques can provide an in-depth understanding in the mechanism of food allergy, which in turn possibly provides a strategy to adapt in the reduction of food immunoreactivity for the food industries.
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Affiliation(s)
- Xin Dong
- Department of Bioresource Engineering, Faculty of Agricultural and Environmental Sciences, McGill University, Sainte-Anne-de-Bellevue, Quebec, Canada
| | - Jin Wang
- Department of Bioresource Engineering, Faculty of Agricultural and Environmental Sciences, McGill University, Sainte-Anne-de-Bellevue, Quebec, Canada
| | - Vijaya Raghavan
- Department of Bioresource Engineering, Faculty of Agricultural and Environmental Sciences, McGill University, Sainte-Anne-de-Bellevue, Quebec, Canada
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Tang HHF, Sly PD, Holt PG, Holt KE, Inouye M. Systems biology and big data in asthma and allergy: recent discoveries and emerging challenges. Eur Respir J 2020; 55:13993003.00844-2019. [PMID: 31619470 DOI: 10.1183/13993003.00844-2019] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Accepted: 09/12/2019] [Indexed: 12/15/2022]
Abstract
Asthma is a common condition caused by immune and respiratory dysfunction, and it is often linked to allergy. A systems perspective may prove helpful in unravelling the complexity of asthma and allergy. Our aim is to give an overview of systems biology approaches used in allergy and asthma research. Specifically, we describe recent "omic"-level findings, and examine how these findings have been systematically integrated to generate further insight.Current research suggests that allergy is driven by genetic and epigenetic factors, in concert with environmental factors such as microbiome and diet, leading to early-life disturbance in immunological development and disruption of balance within key immuno-inflammatory pathways. Variation in inherited susceptibility and exposures causes heterogeneity in manifestations of asthma and other allergic diseases. Machine learning approaches are being used to explore this heterogeneity, and to probe the pathophysiological patterns or "endotypes" that correlate with subphenotypes of asthma and allergy. Mathematical models are being built based on genomic, transcriptomic and proteomic data to predict or discriminate disease phenotypes, and to describe the biomolecular networks behind asthma.The use of systems biology in allergy and asthma research is rapidly growing, and has so far yielded fruitful results. However, the scale and multidisciplinary nature of this research means that it is accompanied by new challenges. Ultimately, it is hoped that systems medicine, with its integration of omics data into clinical practice, can pave the way to more precise, personalised and effective management of asthma.
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Affiliation(s)
- Howard H F Tang
- Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Australia .,Cambridge Baker Systems Genomics Initiative, Dept of Public Health and Primary Care, University of Cambridge, Cambridge, UK.,School of BioSciences, The University of Melbourne, Parkville, Australia
| | - Peter D Sly
- Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, Australia.,Telethon Kids Institute, University of Western Australia, Perth, Australia
| | - Patrick G Holt
- Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, Australia.,Telethon Kids Institute, University of Western Australia, Perth, Australia
| | - Kathryn E Holt
- Dept of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Australia.,London School of Hygiene and Tropical Medicine, London, UK
| | - Michael Inouye
- Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Australia.,Cambridge Baker Systems Genomics Initiative, Dept of Public Health and Primary Care, University of Cambridge, Cambridge, UK.,School of BioSciences, The University of Melbourne, Parkville, Australia.,The Alan Turing Institute, London, UK
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Abstract
The prevalence of food allergy is raising in industrialized countries, but the mechanisms behind this increased incidence are not fully understood. Environmental factors are believed to play a role in allergic diseases, including lifestyle influences, such as diet. There is a close relationship between allergens and lipids, with many allergenic proteins having the ability to bind lipids. Dietary lipids exert pro-inflammatory or anti-inflammatory functions on cells of the innate immunity and influence antigen presentation to cells of the adaptive immunity. In addition to modifying the immunostimulating properties of proteins, lipids also alter their digestibility and intestinal absorption, changing allergen bioavailability. This study provides an overview of the role of dietary lipids in food allergy, taking into account epidemiological information, as well as results of mechanistic investigations using in vivo, ex vivo and in vitro models. The emerging link among high-fat diets, obesity, and allergy is also discussed.
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Affiliation(s)
- Rosina López-Fandiño
- Instituto de Investigación en Ciencias de la Alimentación (CIAL, CSIC-UAM), Madrid, Spain
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39
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Scherf KA, Lindenau AC, Valentini L, Collado MC, García-Mantrana I, Christensen M, Tomsitz D, Kugler C, Biedermann T, Brockow K. Cofactors of wheat-dependent exercise-induced anaphylaxis do not increase highly individual gliadin absorption in healthy volunteers. Clin Transl Allergy 2019; 9:19. [PMID: 30962874 PMCID: PMC6432753 DOI: 10.1186/s13601-019-0260-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 03/11/2019] [Indexed: 12/12/2022] Open
Abstract
Background In wheat-dependent exercise-induced anaphylaxis (WDEIA), cofactors such as exercise, acetylsalicylic acid (ASA), alcohol or unfavorable climatic conditions are required to elicit a reaction to wheat products. The mechanism of action of these cofactors is unknown, but an increase of gliadin absorption has been speculated. Our objectives were to study gliadin absorption with and without cofactors and to correlate plasma gliadin levels with factors influencing protein absorption in healthy volunteers.
Methods Twelve healthy probands (six males, six females; aged 20–56 years) ingested 32 g of gluten without any cofactor or in combination with cofactors aerobic and anaerobic exercise, ASA, alcohol and pantoprazole. Gliadin serum levels were measured up to 120 min afterwards and the intestinal barrier function protein zonulin in stool was collected before and after the procedure; both were measured by ELISA. Stool microbiota profile was obtained by 16S gene sequencing.
Results Within 15 min after gluten intake, gliadin concentrations in blood serum increased from baseline in all subjects reaching highly variable peak levels after 15–90 min. Addition of cofactors did not lead to substantially higher gliadin levels, although variability of levels was higher with differences between individuals (p < 0.001) and increased levels at later time points. Zonulin levels in stool were associated neither with addition of cofactors nor with peak gliadin concentrations. There were no differences in gut microbiota between the different interventions, although the composition of microbiota (p < 0.001) and the redundancy discriminant analysis (p < 0.007) differed in probands with low versus high stool zonulin levels. Conclusion The adsorption of gliadin in the gut in healthy volunteers is less dependent on cofactors than has been hypothesized. Patients with WDEIA may have a predisposition needed for the additional effect of cofactors, e.g., hyperresponsive or damaged intestinal epithelium. Alternatively, other mechanisms, such as cofactor-induced blood flow redistribution, increased activity of tissue transglutaminase, or increases in plasma osmolality and acidosis inducing basophil and mast cell histamine release may play the major role in WDEIA.
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Affiliation(s)
- Katharina Anne Scherf
- 1Leibniz-Institute for Food Systems Biology, Technical University of Munich, Lise-Meitner-Strasse 34, 85354 Freising, Germany
| | - Ann-Christin Lindenau
- 2Department of Agriculture and Food Sciences, Section of Dietetics, University of Applied Sciences Neubrandenburg, Brodaer Str. 2, 17033 Neubrandenburg, Germany
| | - Luzia Valentini
- 2Department of Agriculture and Food Sciences, Section of Dietetics, University of Applied Sciences Neubrandenburg, Brodaer Str. 2, 17033 Neubrandenburg, Germany
| | - Maria Carmen Collado
- 3Department of Biotechnology, Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Av. Catedrático Agustín Escardino 7, 46980 Valencia, Spain
| | - Izaskun García-Mantrana
- 3Department of Biotechnology, Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Av. Catedrático Agustín Escardino 7, 46980 Valencia, Spain
| | - Morten Christensen
- 4Department of Dermatology and Allergy Centre, Odense Research Center for Anaphylaxis (ORCA), Odense University Hospital, 5000 Odense, Denmark
| | - Dirk Tomsitz
- 5Department of Dermatology and Allergy Biederstein, Technical University of Munich, Biedersteiner Strasse 29, 80802 Munich, Germany
| | - Claudia Kugler
- 5Department of Dermatology and Allergy Biederstein, Technical University of Munich, Biedersteiner Strasse 29, 80802 Munich, Germany
| | - Tilo Biedermann
- 5Department of Dermatology and Allergy Biederstein, Technical University of Munich, Biedersteiner Strasse 29, 80802 Munich, Germany
| | - Knut Brockow
- 5Department of Dermatology and Allergy Biederstein, Technical University of Munich, Biedersteiner Strasse 29, 80802 Munich, Germany
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40
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Scherf KA. Immunoreactive cereal proteins in wheat allergy, non-celiac gluten/wheat sensitivity (NCGS) and celiac disease. Curr Opin Food Sci 2019. [DOI: 10.1016/j.cofs.2019.02.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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41
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McClements DJ. Feeding the World Inside Us: Our Gut Microbiomes, Diet, and Health. FUTURE FOODS 2019. [DOI: 10.1007/978-3-030-12995-8_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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42
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43
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Kim WG, Kang GD, Kim HI, Han MJ, Kim DH. Bifidobacterium longum IM55 and Lactobacillus plantarum IM76 alleviate allergic rhinitis in mice by restoring Th2/Treg imbalance and gut microbiota disturbance. Benef Microbes 2018; 10:55-67. [PMID: 30465441 DOI: 10.3920/bm2017.0146] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
This study aimed to examine whether probiotics, which suppressed the differentiation of splenic T cells into type 2 helper T (Th2) cells and induced into regulatory T cells in vitro, alleviate allergic rhinitis (AR) and gut microbiota disturbance. We isolated Bifidobacterium longum IM55 and Lactobacillus plantarum IM76 from human faecal microbiota and kimchi, respectively, and examined their effects on ovalbumin (OVA)-induced AR and gut microbiota disturbance in mice. Treatment with IM55, IM76, or their probiotic mixture (PM) significantly reduced OVA-induced allergic nasal symptoms and blood immunoglobulin E (IgE) levels in mice. These also reduced OVA-induced interleukin (IL)-4 and IL-5 levels in nasal tissues and bronchoalveolar lavage fluid (BALF) but increased OVA-suppressed IL-10 levels. Treatment with IM55, IM76, or PM reduced OVA-induced increase in the populations of mast cells, eosinophils, and Th2 cells and increased OVA-suppressed population of regulatory T cells in the BALF. Treatment with IM55, IM76, or PM also inhibited OVA-induced expression of IL-5 in lung and colon tissues and restored OVA-disturbed composition of gut microbiota Proteobacteria, Bacteroidetes, and Actinobacteria. These results suggest that IM55 and IM67 can alleviate AR by restoring Th2/Treg imbalance and gut microbiota disturbance.
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Affiliation(s)
- W-G Kim
- 1 Department of Food and Nutrition, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
| | - G-D Kang
- 2 Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
| | - H I Kim
- 1 Department of Food and Nutrition, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
| | - M J Han
- 1 Department of Food and Nutrition, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
| | - D-H Kim
- 2 Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.,3 Neurobiota Research Center, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
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Kusari A, Han A, Eichenfield L. Recent advances in understanding and preventing peanut and tree nut hypersensitivity. F1000Res 2018; 7:F1000 Faculty Rev-1716. [PMID: 30467518 PMCID: PMC6208566 DOI: 10.12688/f1000research.14450.1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/17/2018] [Indexed: 12/17/2022] Open
Abstract
Peanut allergy, the most persistent and deadly of the food allergies, has become more prevalent worldwide in recent decades. Numerous explanations have been offered for the rise in peanut allergy, which has been more pronounced in Western, industrialized nations. In infants who are at increased risk of peanut allergy, new evidence indicates that early introduction of peanuts can help prevent allergy development. This counterintuitive finding directly contradicts the previously established practice of peanut avoidance for high-risk infants but is supported by clinical and basic science evidence. Here, we review the literature contributing to our evolving understanding of nut allergy, emphasizing the translation of this work to clinical practice.
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Affiliation(s)
- Ayan Kusari
- Departments of Pediatric and Adolescent Dermatology, Rady Children’s Hospital, San Diego, California, USA
- Department of Dermatology, University of California, San Diego School of Medicine, San Diego, California, USA
| | - Allison Han
- Departments of Pediatric and Adolescent Dermatology, Rady Children’s Hospital, San Diego, California, USA
- Department of Dermatology, University of California, San Diego School of Medicine, San Diego, California, USA
| | - Lawrence Eichenfield
- Departments of Pediatric and Adolescent Dermatology, Rady Children’s Hospital, San Diego, California, USA
- Department of Dermatology, University of California, San Diego School of Medicine, San Diego, California, USA
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45
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Fazlollahi M, Chun Y, Grishin A, Wood RA, Burks AW, Dawson P, Jones SM, Leung DY, Sampson HA, Sicherer SH, Bunyavanich S. Early-life gut microbiome and egg allergy. Allergy 2018; 73:1515-1524. [PMID: 29318631 PMCID: PMC6436531 DOI: 10.1111/all.13389] [Citation(s) in RCA: 155] [Impact Index Per Article: 22.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/23/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Gut microbiota may play a role in egg allergy. We sought to examine the association between early-life gut microbiota and egg allergy. METHODS We studied 141 children with egg allergy and controls from the multicenter Consortium of Food Allergy Research study. At enrollment (age 3 to 16 months), fecal samples were collected, and clinical evaluation, egg-specific IgE measurement, and egg skin prick test were performed. Gut microbiome was profiled by 16S rRNA sequencing. Analyses for the primary outcome of egg allergy at enrollment, and the secondary outcomes of egg sensitization at enrollment and resolution of egg allergy by age 8 years, were performed using Quantitative Insights into Microbial Ecology, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States, and Statistical Analysis of Metagenomic Profiles. RESULTS Compared to controls, increased alpha diversity and distinct taxa (PERMANOVA P = 5.0 × 10-4 ) characterized the early-life gut microbiome of children with egg allergy. Genera from the Lachnospiraceae, Streptococcaceae, and Leuconostocaceae families were differentially abundant in children with egg allergy. Predicted metagenome functional analyses showed differential purine metabolism by the gut microbiota of egg-allergic subjects (Kruskal-Wallis Padj = 0.021). Greater gut microbiome diversity and genera from Lachnospiraceae and Ruminococcaceae were associated with egg sensitization (PERMANOVA P = 5.0 × 10-4 ). Among those with egg allergy, there was no association between early-life gut microbiota and egg allergy resolution by age 8 years. CONCLUSION The distinct early-life gut microbiota in egg-allergic and egg-sensitized children identified by our study may point to targets for preventive or therapeutic intervention.
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Affiliation(s)
- Mina Fazlollahi
- Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Yoojin Chun
- Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Alexander Grishin
- Division of Pediatric Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Robert A. Wood
- Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA
| | - A. Wesley Burks
- Department of Pediatrics, University of North Carolina, Chapel Hill, NC
| | | | - Stacie M. Jones
- Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children’s Hospital, Little Rock, AR, USA
| | | | - Hugh A. Sampson
- Division of Pediatric Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Scott H. Sicherer
- Division of Pediatric Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Supinda Bunyavanich
- Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Division of Pediatric Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Rizzetto L, Fava F, Tuohy KM, Selmi C. Connecting the immune system, systemic chronic inflammation and the gut microbiome: The role of sex. J Autoimmun 2018; 92:12-34. [PMID: 29861127 DOI: 10.1016/j.jaut.2018.05.008] [Citation(s) in RCA: 235] [Impact Index Per Article: 33.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 05/18/2018] [Accepted: 05/21/2018] [Indexed: 12/12/2022]
Abstract
Unresolved low grade systemic inflammation represents the underlying pathological mechanism driving immune and metabolic pathways involved in autoimmune diseases (AID). Mechanistic studies in animal models of AID and observational studies in patients have found alterations in gut microbiota communities and their metabolites, suggesting a microbial contribution to the onset or progression of AID. The gut microbiota and its metabolites have been shown to influence immune functions and immune homeostasis both within the gut and systematically. Microbial derived-short chain fatty acid (SCFA) and bio-transformed bile acid (BA) have been shown to influence the immune system acting as ligands specific cell signaling receptors like GPRCs, TGR5 and FXR, or via epigenetic processes. Similarly, intestinal permeability (leaky gut) and bacterial translocation are important contributors to chronic systemic inflammation and, without repair of the intestinal barrier, might represent a continuous inflammatory stimulus capable of triggering autoimmune processes. Recent studies indicate gender-specific differences in immunity, with the gut microbiota shaping and being concomitantly shaped by the hormonal milieu governing differences between the sexes. A bi-directional cross-talk between microbiota and the endocrine system is emerging with bacteria being able to produce hormones (e.g. serotonin, dopamine and somatostatine), respond to host hormones (e.g. estrogens) and regulate host hormones' homeostasis (e.g by inhibiting gene prolactin transcription or converting glucocorticoids to androgens). We review herein how gut microbiota and its metabolites regulate immune function, intestinal permeability and possibly AID pathological processes. Further, we describe the dysbiosis within the gut microbiota observed in different AID and speculate how restoring gut microbiota composition and its regulatory metabolites by dietary intervention including prebiotics and probiotics could help in preventing or ameliorating AID. Finally, we suggest that, given consistent observations of microbiota dysbiosis associated with AID and the ability of SCFA and BA to regulate intestinal permeability and inflammation, further mechanistic studies, examining how dietary microbiota modulation can protect against AID, hold considerable potential to tackle increased incidence of AID at the population level.
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Affiliation(s)
- Lisa Rizzetto
- Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, San Michele all'Adige, Trento, Italy.
| | - Francesca Fava
- Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, San Michele all'Adige, Trento, Italy
| | - Kieran M Tuohy
- Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, San Michele all'Adige, Trento, Italy
| | - Carlo Selmi
- Division of Rheumatology and Clinical Immunology, Humanitas Research Hospital, Rozzano, Italy; BIOMETRA Department, University of Milan, Italy
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47
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Abstract
The developmental origin of health and disease highlights the importance of the period of the first 1000 days (from the conception to the 2 years of life). The process of the gut microbiota establishment is included in this time window. Various perinatal determinants, such as cesarean section delivery, type of feeding, antibiotics treatment, gestational age or environment, can affect the pattern of bacterial colonization and result in dysbiosis. The alteration of the early bacterial gut pattern can persist over several months and may have long-lasting functional effects with an impact on disease risk later in life. As for example, early gut dysbiosis has been involved in allergic diseases and obesity occurrence. Besides, while it was thought that the fetus developed under sterile conditions, recent data suggested the presence of a microbiota in utero, particularly in the placenta. Even if the origin of this microbiota and its eventual transfer to the infant are nowadays unknown, this placental microbiota could trigger immune responses in the fetus and would program the infant's immune development during fetal life, earlier than previously considered. Moreover, several studies demonstrated a link between the composition of placental microbiota and some pathological conditions of the pregnancy. All these data show the evidence of relationships between the neonatal gut establishment and future health outcomes. Hence, the use of pre- and/or probiotics to prevent or repair any early dysbiosis is increasingly attractive to avoid long-term health consequences.
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48
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Kim JA, Kim SH, Kim IS, Yu DY, Kim SC, Lee SH, Lee SS, Yun CH, Choi IS, Cho KK. Anti-Inflammatory Effects of a Mixture of Lactic Acid Bacteria and Sodium Butyrate in Atopic Dermatitis Murine Model. J Med Food 2018; 21:716-725. [PMID: 29648971 DOI: 10.1089/jmf.2017.4116] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Atopic dermatitis is a chronic and recurrent inflammatory skin disease. Recently, probiotics have been shown to suppress allergic symptoms through immunomodulatory responses. In the present study, combinatorial effects on allergic symptoms were identified in BALB/c mice fed with a mixture of four species of probiotics, Bifidobacterium lactis, Lactobacillus casei, Lactobacillus rhamnosus, and Lactobacillus plantarum, and sodium butyrate. Following sensitization with whey protein, the mice were challenged and divided into two groups: (1) mice administered with phosphate-buffered saline as a control and (2) mice administered with the probiotic mixture and sodium butyrate. Allergic symptoms were assessed by measuring ear thicknesses, serum histamine and IL-10 concentrations, and the quantities of leaked Evans blue. T cell differentiation was determined by analyzing the T cells groups in the mesenteric lymph nodes (MLNs) and spleen. To examine changes in the total gut microbiota, total fecal microflora was isolated, species identification was performed by DNA sequencing using Illumina MiSeq, and changes in intestinal beneficial bacteria were analyzed using quantitative polymerase chain reaction. Treatment with the probiotic mixture and sodium butyrate reduced ear thicknesses, the quantity of leaked Evans blue, and serum histamine values, while increasing serum IL-10 values. In the mouse model, the probiotic mixture and sodium butyrate increased Th1 and Treg cell differentiation in MLN and spleen tissues; the ratio of Firmicutes/Bacteroidetes, which is associated with reduction in allergic reactions; and microorganisms that lead to cell differentiation into Treg. These results suggest that the probiotic mixture and sodium butyrate can prevent and alleviate allergic symptoms.
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Affiliation(s)
- Jeong A Kim
- 1 Department of Animal Resources Technology, Gyeongnam National University of Science and Technology , Jinju, Korea
| | - Sung-Hak Kim
- 2 Department of Animal Science, Chonnam National University , Gwangju, Korea
| | - In Sung Kim
- 1 Department of Animal Resources Technology, Gyeongnam National University of Science and Technology , Jinju, Korea
| | - Da Yoon Yu
- 1 Department of Animal Resources Technology, Gyeongnam National University of Science and Technology , Jinju, Korea
| | - Sung Chan Kim
- 3 Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University , Chuncheon, Korea
| | - Seung Ho Lee
- 4 Department of Nano-Bioengineering, Incheon National University , Incheon, Korea
| | - Sang Suk Lee
- 5 Department of Animal Science and Technology, Sunchon National University , Sunchon, Korea
| | - Cheol-Heui Yun
- 6 Department of Agricultural Biotechnology, Seoul National University , Seoul, Korea
| | - In Soon Choi
- 7 Department of Life Science, Silla University , Busan, Korea
| | - Kwang Keun Cho
- 1 Department of Animal Resources Technology, Gyeongnam National University of Science and Technology , Jinju, Korea
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49
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Abstract
Advances in food allergy diagnosis, management, prevention, and therapeutic interventions have been significant over the past 2 decades. Evidence-based national and international guidelines have streamlined food allergy diagnosis and management, whereas paradigm-shifting work in primary prevention of peanut allergy has resulted in significant modifications in the approach to early food introduction in infants and toddlers. Innovative investigation of food allergy epidemiology, systems biology, effect, and management has provided important insights. Although active therapeutic approaches to food allergy remain experimental, progress toward licensed therapies has been substantial. Mechanistic understanding of the immunologic processes underlying food allergy and immunotherapy will inform the future design of therapeutic approaches targeting the food-induced allergic response. Global strategies to mitigate the substantial medical, economic, and psychosocial burden of food allergy in affected subjects and families will require engagement of stakeholders across multiple sectors in research, health care, public health, government, educational institutions, and industry. However, the relationship between the well-informed allergy care provider and the patient and family remains fundamental for optimizing the care of the patient with food allergy.
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Affiliation(s)
- Amy M Scurlock
- Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, Ark
| | - Stacie M Jones
- Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, Ark.
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50
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Tham EH, Leung DYM. Global perspectives on food allergy: One size doesn't fit all. Ann Allergy Asthma Immunol 2018; 120:234-236. [PMID: 29398243 DOI: 10.1016/j.anai.2017.11.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Revised: 11/09/2017] [Accepted: 11/10/2017] [Indexed: 12/14/2022]
Affiliation(s)
- Elizabeth Huiwen Tham
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore; Department of Pediatrics, National Jewish Health, Denver, Colorado
| | - Donald Y M Leung
- Department of Pediatrics, National Jewish Health, Denver, Colorado.
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