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Bai J, Zeng Q, Den W, Huang L, Wu Z, Li X, Tong P, Chen H, Yang A. Synergistic Synbiotic-Containing Lactiplantibacillus plantarum and Fructo-Oligosaccharide Alleviate the Allergenicity of Mice Induced by Soy Protein. Foods 2025; 14:109. [PMID: 39796399 PMCID: PMC11720218 DOI: 10.3390/foods14010109] [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: 11/07/2024] [Revised: 11/30/2024] [Accepted: 12/27/2024] [Indexed: 01/13/2025] Open
Abstract
Prebiotics and probiotics have key roles in the intervention and treatment of food allergies. This study assesses the effect of Lactiplantibacillus plantarum synergistic fructo-oligosaccharide (Lp-FOS) intervention using an allergic mouse model induced by soy protein. The results showed that Lp synergistic FOS significantly decreased clinical allergy scores, inhibited specific antibodies (IgE, IgG, and IgG1), IL-4, IL-6, and IL-17A levels, and increased IFN-γ and IL-10 levels. Meanwhile, flow cytometry showed that Lp-FOS intervention inhibited the percentage of dendritic cell (DC) subsets in splenocytes and increased the Th1/Th2 and Treg/Th17 ratios. Furthermore, Lp-FOS intervention upregulated the mRNA levels of T-bet and Foxp3 and downregulated the mRNA levels of GATA3. Finally, non-targeted metabolomic analysis showed that Lp-FOS improved serum metabolic disorders caused by food allergies through regulating glycine, serine, and threonine metabolism, butanoate metabolism, glyoxylate and dicarboxylate metabolism, the biosynthesis of cofactors, and glycerophospholipid metabolism. These data showed that the combination formulation Lp-FOS could be a promising adjuvant treatment for food allergies.
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Affiliation(s)
- Jing Bai
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China; (J.B.); (Q.Z.); (W.D.); (L.H.); (Z.W.); (X.L.); (P.T.); (H.C.)
- School of Food Science and Technology, Nanchang University, Nanchang 330047, China
- Sino-German Joint Research Institute, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China
| | - Qian Zeng
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China; (J.B.); (Q.Z.); (W.D.); (L.H.); (Z.W.); (X.L.); (P.T.); (H.C.)
- School of Food Science and Technology, Nanchang University, Nanchang 330047, China
- Sino-German Joint Research Institute, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China
| | - Wen Den
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China; (J.B.); (Q.Z.); (W.D.); (L.H.); (Z.W.); (X.L.); (P.T.); (H.C.)
- School of Food Science and Technology, Nanchang University, Nanchang 330047, China
- Sino-German Joint Research Institute, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China
| | - Liheng Huang
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China; (J.B.); (Q.Z.); (W.D.); (L.H.); (Z.W.); (X.L.); (P.T.); (H.C.)
- School of Food Science and Technology, Nanchang University, Nanchang 330047, China
- Sino-German Joint Research Institute, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China
| | - Zhihua Wu
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China; (J.B.); (Q.Z.); (W.D.); (L.H.); (Z.W.); (X.L.); (P.T.); (H.C.)
- Sino-German Joint Research Institute, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China
| | - Xin Li
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China; (J.B.); (Q.Z.); (W.D.); (L.H.); (Z.W.); (X.L.); (P.T.); (H.C.)
- School of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Ping Tong
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China; (J.B.); (Q.Z.); (W.D.); (L.H.); (Z.W.); (X.L.); (P.T.); (H.C.)
| | - Hongbing Chen
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China; (J.B.); (Q.Z.); (W.D.); (L.H.); (Z.W.); (X.L.); (P.T.); (H.C.)
- Sino-German Joint Research Institute, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China
| | - Anshu Yang
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China; (J.B.); (Q.Z.); (W.D.); (L.H.); (Z.W.); (X.L.); (P.T.); (H.C.)
- Sino-German Joint Research Institute, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China
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Abdul Kalam Saleena L, Chang SK, Simarani K, Arunachalam KD, Thammakulkrajang R, How YH, Pui LP. A comprehensive review of Bifidobacterium spp: as a probiotic, application in the food and therapeutic, and forthcoming trends. Crit Rev Microbiol 2024; 50:581-597. [PMID: 37551693 DOI: 10.1080/1040841x.2023.2243617] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 07/03/2023] [Accepted: 07/26/2023] [Indexed: 08/09/2023]
Abstract
Recently, more consumers are interested in purchasing probiotic food and beverage products that may improve their immune health. The market for functional foods and beverages that include Bifidobacterium is expanding because of their potential uses in both food and therapeutic applications. However, maintaining Bifidobacterium's viability during food processing and storage remains a challenge. Microencapsulation technique has been explored to improve the viability of Bifidobacterium. Despite the technical, microbiological, and economic challenges, the market potential for immune-supporting functional foods and beverages is significant. Additionally, there is a shift toward postbiotics as a solution for product innovation, a promising postbiotic product that can be incorporated into various food and beverage formats is also introduced in this review. As consumers become more health-conscious, future developments in the functional food and beverage market discussed in this review could serve as a reference for researchers and industrialist.
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Affiliation(s)
| | - Sui Kiat Chang
- Department of Allied Health Sciences, Faculty of Science, Universiti Tunku Abdul Rahman Kampar, Perak, Malaysia
| | - Khanom Simarani
- Faculty of Science, Institute Biological Sciences, University of Malaya, Kuala Lumpur, Malaysia
| | - Kantha Deivi Arunachalam
- Directorate of Research, Center For Environmental Nuclear Research, SRM Institute of Science and Technology, SRM Nagar, Chennai, India
- Faculty of Sciences, Marwadi University, Rajkot, India
| | | | - Yu Hsuan How
- Department of Food Science and Nutrition, Faculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia
| | - Liew Phing Pui
- Department of Food Science and Nutrition, Faculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia
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Li Q, Deng Y, Xu Z, Zhou H. Combined transcriptomics and TMT-proteomics reveal abnormal complement and coagulation cascades in cow's milk protein allergy. Int Immunopharmacol 2024; 131:111806. [PMID: 38457985 DOI: 10.1016/j.intimp.2024.111806] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 02/28/2024] [Accepted: 03/04/2024] [Indexed: 03/10/2024]
Abstract
Cow's milk protein allergy (CMPA) is primarily due to the inability of the intestinal mucosa to establish typical immunological tolerance to proteins found in cow's milk, and the specific molecular mechanism is still unclear. In order to investigate molecular alterations in intestinal tissues during CMPA occurrence, this study analyzed the jejunal tissue of β-lactoglobulin (BLG)-sensitized mice through transcriptomics and quantitative tandem mass tag (TMT)-labeled proteomics. A total of 475 differentially expressed genes (256 up-regulated, 219 down-regulated) and 94 differentially expressed proteins (65 up-regulated, 29 down-regulated) were identified. Comparing the KEGG pathways of the two groups, it was found that both were markedly enriched in the signaling pathways of complement and coagulation cascade. Among these, kallikrein B1 (KLKB1) in this pathway is speculated to be pivotal in CMPA. It may potentially enhance the release of bradykinin by activating the kallikrein-kinin system, leading to pro-inflammatory effects and exacerbating intestinal mucosal damage. This study suggests that the pathways of complement and coagulation cascades could be significant in the context of intestinal immunity in CMPA, and KLKB1 may be its potential therapeutic target.
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Affiliation(s)
- Qunchao Li
- Department of Pediatrics, Provincial Hospital Affiliated to Anhui Medical University, Hefei, China
| | - Yan Deng
- School of Medicine, Anhui University of Science and Technology, Huainan, China
| | - Zhiwei Xu
- Bengbu Medical College, Bengbu, China
| | - Haoquan Zhou
- Department of Pediatrics, Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.
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Han X, Chang L, Chen H, Zhao J, Tian F, Ross RP, Stanton C, van Sinderen D, Chen W, Yang B. Harnessing the endogenous Type I-C CRISPR-Cas system for genome editing in Bifidobacterium breve. Appl Environ Microbiol 2024; 90:e0207423. [PMID: 38319094 PMCID: PMC10952402 DOI: 10.1128/aem.02074-23] [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: 11/27/2023] [Accepted: 01/14/2024] [Indexed: 02/07/2024] Open
Abstract
Bifidobacterium breve, one of the main bifidobacterial species colonizing the human gastrointestinal tract in early life, has received extensive attention for its purported beneficial effects on human health. However, exploration of the mode of action of such beneficial effects exerted by B. breve is cumbersome due to the lack of effective genetic tools, which limits its synthetic biology application. The widespread presence of CRISPR-Cas systems in the B. breve genome makes endogenous CRISPR-based gene editing toolkits a promising tool. This study revealed that Type I-C CRISPR-Cas systems in B. breve can be divided into two groups based on the amino acid sequences encoded by cas gene clusters. Deletion of the gene coding uracil phosphoribosyl-transferase (upp) was achieved in five B. breve strains from both groups using this system. In addition, translational termination of uracil phosphoribosyl-transferase was successfully achieved in B. breve FJSWX38M7 by single-base substitution of the upp gene and insertion of three stop codons. The gene encoding linoleic acid isomerase (bbi) in B. breve, being a characteristic trait, was deleted after plasmid curing, which rendered it unable to convert linoleic acid into conjugated linoleic acid, demonstrating the feasibility of successive editing. This study expands the toolkit for gene manipulation in B. breve and provides a new approach toward functional genome editing and analysis of B. breve strains.IMPORTANCEThe lack of effective genetic tools for Bifidobacterium breve is an obstacle to studying the molecular mechanisms of its health-promoting effects, hindering the development of next-generation probiotics. Here, we introduce a gene editing method based on the endogenous CRISPR-Cas system, which can achieve gene deletion, single-base substitution, gene insertion, and successive gene editing in B. breve. This study will facilitate discovery of functional genes and elucidation of molecular mechanisms of B. breve pertaining to health-associated benefits.
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Affiliation(s)
- Xiao Han
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| | - Lulu Chang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| | - Haiqin Chen
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| | - Fengwei Tian
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- International Joint Research Center for Probiotics & Gut Health, Jiangnan University, Wuxi, Jiangsu, China
| | - R. Paul Ross
- International Joint Research Center for Probiotics & Gut Health, Jiangnan University, Wuxi, Jiangsu, China
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Catherine Stanton
- International Joint Research Center for Probiotics & Gut Health, Jiangnan University, Wuxi, Jiangsu, China
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | | | - Wei Chen
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu, China
| | - Bo Yang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- International Joint Research Center for Probiotics & Gut Health, Jiangnan University, Wuxi, Jiangsu, China
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Liang X, Diao E, Qian S, Song H, Xiang X, Gou X, Hu X. Comparative metabolomic analysis and antigenicity comparison of cow milk and enzymatically treated cow milk. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2024; 104:536-545. [PMID: 37621148 DOI: 10.1002/jsfa.12927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 08/09/2023] [Accepted: 08/25/2023] [Indexed: 08/26/2023]
Abstract
BACKGROUND Amino acids (AAs) are important protein building blocks that play a critical role in the function of the immune system. However, comprehensive comparative metabolomics and antigenicity analyses of cow milk (CM) and enzymatically treated CM are relatively scarce. This study analyzed the AAs in the CM and Flavourzyme-treated milk groups (FT), and their antigenicity was also explored. RESULTS Overall, 50 AAs were detected in the CM and FT groups, with 23 significantly different AAs. The interaction network of these significantly different AAs was analyzed, and 34 significantly different metabolic pathways were found to be involved. It was also found that the antigenicity of the FT group was significantly reduced in comparison with that of the CM group. CONCLUSION These results enhance our understanding of AAs and antigenicity regarding CM and FT, and provide new ideas and directions for the development of high-quality hypoallergenic dairy products. © 2023 Society of Chemical Industry.
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Affiliation(s)
- Xiaona Liang
- Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Jiangsu Key Laboratory for Food Safety & Nutrition Function Evaluation, Huaiyin Normal University, Huaian, China
- School of Life Science, Huaiyin Normal University, Huaian, China
| | - Enjie Diao
- Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Jiangsu Key Laboratory for Food Safety & Nutrition Function Evaluation, Huaiyin Normal University, Huaian, China
- School of Life Science, Huaiyin Normal University, Huaian, China
| | - Shiquan Qian
- Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Jiangsu Key Laboratory for Food Safety & Nutrition Function Evaluation, Huaiyin Normal University, Huaian, China
- School of Life Science, Huaiyin Normal University, Huaian, China
| | - Huwei Song
- Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Jiangsu Key Laboratory for Food Safety & Nutrition Function Evaluation, Huaiyin Normal University, Huaian, China
- School of Life Science, Huaiyin Normal University, Huaian, China
| | - Xinran Xiang
- Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Jiangsu Key Laboratory for Food Safety & Nutrition Function Evaluation, Huaiyin Normal University, Huaian, China
- School of Life Science, Huaiyin Normal University, Huaian, China
| | - Xiurong Gou
- School of Life Science, Huaiyin Normal University, Huaian, China
| | - Xiumin Hu
- School of Life Science, Huaiyin Normal University, Huaian, China
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Wang Z, Wu Q, Guan M, Li Z, Pan W, Tang W. Investigation of gut microbiota changes and allergic inflammation of mice with milk protein-induced allergic enteritis. FEMS Microbiol Lett 2024; 371:fnad127. [PMID: 38066685 DOI: 10.1093/femsle/fnad127] [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: 09/07/2023] [Revised: 11/03/2023] [Accepted: 12/07/2023] [Indexed: 01/11/2024] Open
Abstract
This study aimed to investigate the changes of gut microbiota and allergic inflammation in mice with allergic enteritis caused by milk protein. In this study, female BALB\C mice in the whey protein (WP-sensitized) group were gavaged with WP and normal saline, the sham-sensitized group was given normal saline once a week for 5 weeks. One week later, the WP-sensitized mice were administered 60 mg β-lactoglobulin (BLG). The results showed that mice's body weight decreased, feces with loose and bloody, and systemic allergic reactions and ear swelling increased in the WP-sensitized group. The levels of WP-specific Ig, mMCP-1, calprotectin of feces, and inflammation-related factors in the WP-sensitized group were increased. WP-sensitized group intestine tissues were damaged severely and the expressions of ZO-1, Claudin-1, and Occludin reduced. The results of 16S rRNA sequencing showed that there were differences in operational taxonomic units (OUT) levels of gut microbes between the two groups, o_Clostridiales, c_Clostridia, and f_Lachnospiraceae were more abundant in the WP-sensitized group. In conclusion, the WP sensitization can induce the allergic inflammation, intestinal injury and intestinal barrier dysfunction in mice, and the gut microbes were also changed, which provided a reference for the treatment of WP-sensitized mice.
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Affiliation(s)
- Zhongmin Wang
- Department of Gastroenterology, Hangzhou Children's Hospital, Hangzhou, Zhejiang 310014, China
| | - Qiao Wu
- Department of Pediatrics, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, China
| | - Minchang Guan
- Department of Pediatrics, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang 310021, China
| | - Ze Li
- Department of Gastroenterology, Hangzhou Children's Hospital, Hangzhou, Zhejiang 310014, China
| | - Wei Pan
- Department of Gastroenterology, Hangzhou Children's Hospital, Hangzhou, Zhejiang 310014, China
| | - Weihong Tang
- Department of Gastroenterology, Hangzhou Children's Hospital, Hangzhou, Zhejiang 310014, China
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Zuurveld M, Diks MAP, Kiliaan PCJ, Garssen J, Folkerts G, van’t Land B, Willemsen LEM. Butyrate interacts with the effects of 2'FL and 3FL to modulate in vitro ovalbumin-induced immune activation, and 2'FL lowers mucosal mast cell activation in a preclinical model for hen's egg allergy. Front Nutr 2023; 10:1305833. [PMID: 38174112 PMCID: PMC10762782 DOI: 10.3389/fnut.2023.1305833] [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: 10/02/2023] [Accepted: 11/15/2023] [Indexed: 01/05/2024] Open
Abstract
Background Early life provides a window of opportunity to prevent allergic diseases. With a prevalence of 0.5-2% in infants, hen's egg allergy is one of the most common food allergies. The immunomodulatory effects of human milk oligosaccharides (HMOs), 2'-fucosyllactose (2'FL), and 3-fucosyllactose (3FL) were studied in an in vitro mucosal immune model and an in vivo murine model for hen's egg (ovalbumin) allergy. Methods Intestinal epithelial cell (IEC)/dendritic cell (DC) and DC/T cell cocultures were used to expose IECs to ovalbumin (OVA) in an in vitro mucosal immune model. The effects of epithelial pre-incubation with 0.1% 2'FL or 3FL and/or 0.5 mM butyrate were studied. Three- to four-weeks-old female C3H/HeOuJ mice were fed AIN93G diets containing 0.1-0.5% 2'FL or 3FL 2 weeks before and during OVA sensitization and challenge. Allergic symptoms and systemic and local immune parameters were assessed. Results Exposing IECs to butyrate in vitro left the IEC/DC/T cell cross-talk unaffected, while 2'FL and 3FL showed differential immunomodulatory effects. In 3FL exposed IEC-DC-T cells, the secretion of IFNγ and IL10 was enhanced. This was observed upon pre-incubation of IECs with 2'FL and butyrate as well, but not 2'FL alone. The presence of butyrate did not affect OVA activation, but when combined with 3FL, an increase in IL6 release from DCs was observed (p < 0.001). OVA allergic mice receiving 0.5% 3FL diet had a lower %Th2 cells in MLNs, but the humoral response was unaltered compared to control mice. OVA-allergic mice receiving 0.1 or 0.5% 2'FL diets had lower serum levels of OVA-IgG2a (p < 0.05) or the mast cell marker mMCP1, in association with increased concentration of cecal short-chain fatty acids (SCFAs) (p < 0.05). Conclusion In vitro butyrate exposure promotes the development of a downstream type 1 and regulatory response observed after 2'FL exposure. 2'FL and 3FL differentially modulate ovalbumin-induced mucosal inflammation predominantly independent of butyrate. Mice receiving dietary 3FL during ovalbumin sensitization and challenge had lowered Th2 activation while the frequency of Treg cells was enhanced. By contrast, 2'FL improved the humoral immune response and suppressed mast cell activation in association with increased SCFAs production in the murine model for hen's egg allergy.
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Affiliation(s)
- M. Zuurveld
- Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - M. A. P. Diks
- Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - P. C. J. Kiliaan
- Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - J. Garssen
- Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
- Danone Nutricia Research B.V, Utrecht, Netherlands
| | - G. Folkerts
- Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - B. van’t Land
- Danone Nutricia Research B.V, Utrecht, Netherlands
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
| | - L. E. M. Willemsen
- Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
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Lajnaf R, Feki S, Ben Ameur S, Attia H, Kammoun T, Ayadi MA, Masmoudi H. Recent advances in selective allergies to mammalian milk proteins not associated with Cow's Milk Proteins Allergy. Food Chem Toxicol 2023; 178:113929. [PMID: 37406758 DOI: 10.1016/j.fct.2023.113929] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Revised: 06/13/2023] [Accepted: 06/30/2023] [Indexed: 07/07/2023]
Abstract
Cow's milk proteins allergy (CMA) is an atypical immune system response to cow's milk and dairy products. It's one of the most common food allergies in children affecting 8% of the total pediatric population pediatric population. This comprehensive review examines recent studies in CMA, especially regarding mammalian milk allergies such as goat's, sheep's, buffalo's, camel's, mare's and donkey's milk allergies in order to increase awareness of these selective allergies and to reduce allergy risks for those who have them. The consumption of other mammalian milk types is not recommended because of the significant homology between milk proteins from cow, sheep, goat and buffalo resulting in clinical cross-reactivity. However, camel's, mare's or donkey's milk may be tolerated by some allergic patients. Selective mammalian milk allergies are unusual and rare disorders characterized by severe symptoms including angio-oedema, urticaria, respiratory manifestations and anaphylaxis. Based on the reported allergic cases, cheese products including Ricotta, Romano, Pecorino and Mozzarella, are considered as the most common source of allergens especially in goat's, sheep's and buffalo's milk allergies, while the major allergens in donkey's and mare's milk seems to be whey proteins including lysozyme, α-lactalbumin and β-lactogloblin due to the low casein/whey proteins ratio in equine's milk.
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Affiliation(s)
- Roua Lajnaf
- Alimentary Analysis Unit, National Engineering School of Sfax, BPW 3038, Sfax, Tunisia; Immunology Department, Habib Bourguiba University Hospital, Sfax, Tunisia; Pediatric Department, Hédi Chaker University Hospital, Sfax, Tunisia.
| | - Sawsan Feki
- Immunology Department, Habib Bourguiba University Hospital, Sfax, Tunisia
| | - Salma Ben Ameur
- Pediatric Department, Hédi Chaker University Hospital, Sfax, Tunisia
| | - Hamadi Attia
- Alimentary Analysis Unit, National Engineering School of Sfax, BPW 3038, Sfax, Tunisia
| | - Thouraya Kammoun
- Pediatric Department, Hédi Chaker University Hospital, Sfax, Tunisia
| | - Mohamed Ali Ayadi
- Department of Food Technology, University of Liege-Gembloux Agro-Bio Tech, Passage des Déportés, 2, Gembloux, B-5030, Belgium
| | - Hatem Masmoudi
- Immunology Department, Habib Bourguiba University Hospital, Sfax, Tunisia
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Rousseaux A, Brosseau C, Bodinier M. Immunomodulation of B Lymphocytes by Prebiotics, Probiotics and Synbiotics: Application in Pathologies. Nutrients 2023; 15:nu15020269. [PMID: 36678140 PMCID: PMC9863037 DOI: 10.3390/nu15020269] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/22/2022] [Accepted: 01/03/2023] [Indexed: 01/07/2023] Open
Abstract
INTRODUCTION Prebiotics, probiotics and synbiotics are known to have major beneficial effects on human health due to their ability to modify the composition and the function of the gut mucosa, the gut microbiota and the immune system. These components largely function in a healthy population throughout different periods of life to confer homeostasis. Indeed, they can modulate the composition of the gut microbiota by increasing bacteria strands that are beneficial for health, such as Firmicute and Bifidobacteria, and decreasing harmful bacteria, such as Enteroccocus. Their immunomodulation properties have been extensively studied in different innate cells (dendritic cells, macrophages, monocytes) and adaptive cells (Th, Treg, B cells). They can confer a protolerogenic environment but also modulate pro-inflammatory responses. Due to all these beneficial effects, these compounds have been investigated to prevent or to treat different diseases, such as cancer, diabetes, allergies, autoimmune diseases, etc. Regarding the literature, the effects of these components on dendritic cells, monocytes and T cells have been studied and presented in a number of reviews, but their impact on B-cell response has been less widely discussed. CONCLUSIONS For the first time, we propose here a review of the literature on the immunomodulation of B-lymphocytes response by prebiotics, probiotics and synbiotics, both in healthy conditions and in pathologies. DISCUSSION Promising studies have been performed in animal models, highlighting the potential of prebiotics, probiotics and synbiotics intake to treat or to prevent diseases associated with B-cell immunomodulation, but this needs to be validated in humans with a full characterization of B-cell subsets and not only the humoral response.
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Shi J, Wang Y, Cheng L, Wang J, Raghavan V. Gut microbiome modulation by probiotics, prebiotics, synbiotics and postbiotics: a novel strategy in food allergy prevention and treatment. Crit Rev Food Sci Nutr 2022; 64:5984-6000. [PMID: 36576159 DOI: 10.1080/10408398.2022.2160962] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Food allergy has caused lots of global public health issues, particularly in developed countries. Presently, gut microbiota has been widely studied on allergy, while the role of dysbiosis in food allergy remains unknown. Scientists found that changes in gut microbial compositions and functions are strongly associated with a dramatic increase in the prevalence of food allergy. Altering microbial composition is crucial in modulating food antigens' immunogenicity. Thus, the potential roles of probiotics, prebiotics, synbiotics, and postbiotics in affecting gut bacteria communities and the immune system, as innovative strategies against food allergy, begins to attract high attention of scientists. This review briefly summarized the mechanisms of food allergy and discussed the role of the gut microbiota and the use of probiotics, prebiotics, synbiotics, and postbiotics as novel therapies for the prevention and treatment of food allergy. The perspective studies on the development of novel immunotherapy in food allergy were also described. A better understanding of these mechanisms will facilitate the development of preventive and therapeutic strategies for food allergy.
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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, China
| | - Youfa 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, China
| | - Lei Cheng
- Department of Otorhinolaryngology and Clinical Allergy Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 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, China
| | - Vijaya Raghavan
- Department of Bioresource Engineering, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Canada
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11
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Ayechu-Muruzabal V, de Boer M, Blokhuis B, Berends AJ, Garssen J, Kraneveld AD, van’t Land B, Willemsen LEM. Epithelial-derived galectin-9 containing exosomes contribute to the immunomodulatory effects promoted by 2'-fucosyllactose and short-chain galacto- and long-chain fructo-oligosaccharides. Front Immunol 2022; 13:1026031. [PMID: 36685520 PMCID: PMC9846635 DOI: 10.3389/fimmu.2022.1026031] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 12/05/2022] [Indexed: 12/24/2022] Open
Abstract
Introduction Early life exposure to non-digestible oligosaccharides (NDO) or microbial components is known to affect immune development. NDO in combination with a TLR9 agonist mimicking bacterial triggers (CpG) promoted the secretion of galectins through unknown pathways. We aimed to study the contribution of exosomes in epithelial galectin secretion and subsequent immunoregulation upon exposure to a mixture of NDO by inhibiting exosome biogenesis. Methods Human intestinal epithelial cells (IEC) (FHs 74 Int or HT-29) were apically exposed to 2'-fucosyllactose (2'FL) and short-chain galacto- and long-chain fructo-oligosaccharides (GF), alone or with CpG. Basolaterally, non-activated or αCD3/CD28-activated peripheral blood mononuclear cells (PBMC) were added. After 24 h incubation, IEC were washed and incubated in fresh medium to analyze epithelial-derived galectin secretion. Additionally, before exposure to NDO and CpG, IEC were exposed to GW4869 to inhibit exosome biogenesis. After 24 h of incubation, IEC were washed and incubated for additional 24 h in the presence of GW4869, after which epithelial-derived galectin secretion was studied. Also, epithelial-derived exosomes were isolated to study the presence of galectins within the exosomes. Results Compared to CpG alone, exposure to 2'FL/GF mixture and CpG, significantly enhanced Th1-type IFNγ, and regulatory IEC-derived galectin-9 secretion in the HT-29/PBMC model. Similarly, in the FHs 74 Int/PBMC co-culture, 2'FL/GF induced immunomodulatory effects in the absence of CpG. Interestingly, galectin-9 and -4 were present in CD63-expressing exosomes isolated from HT-29 supernatants after IEC/PBMC co-culture. Exposure to GW4869 suppressed 2'FL/GF and CpG induced epithelial-derived galectin-9 secretion, which subsequently prevented the rise in IL-10 and reduction in IL-13 secretion observed in the HT-29/PBMC co-culture model upon exposure to 2'FL/GF and CpG. Discussion Exposure to 2'FL/GF and CpG or 2'FL/GF promoted Th1-type regulatory effects in HT-29/PBMC or FHs 74 Int/PBMC co-culture respectively, while Th2-type IL-13 was reduced in association with increased galectin-9 release. Galectin-9 and -4 were present in exosomes from HT-29 and the inhibition of exosome biogenesis inhibited epithelial-derived galectin secretion. This, also affected immunomodulatory effects in IEC/PBMC co-culture suggesting a key role of galectin expressing IEC-derived exosomes in the mucosal immune regulation induced by NDO.
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Affiliation(s)
- Veronica Ayechu-Muruzabal
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, Netherlands
| | - Merel de Boer
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, Netherlands
| | - Bart Blokhuis
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, Netherlands
| | - Alinda J. Berends
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, Netherlands
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, Netherlands
- Danone Nutricia Research, Utrecht, Netherlands
| | - Aletta D. Kraneveld
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, Netherlands
| | - Belinda van’t Land
- Danone Nutricia Research, Utrecht, Netherlands
- Center for Translational Immunology, The Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, Netherlands
| | - Linette E. M. Willemsen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, Netherlands
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12
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Huang M, Li X, Wu Y, Meng X, Tong P, Yuan J, Yang A, Wu Z, Chen H, Xiong C. Potential allergenicity and hydrolysis assessment of bovine casein and β-casein by treatment with lactic acid bacteria. J Food Biochem 2022; 46:e14424. [PMID: 36197951 DOI: 10.1111/jfbc.14424] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 05/03/2022] [Accepted: 06/30/2022] [Indexed: 01/13/2023]
Abstract
Casein is one of the main allergens in cow's milk, accounting for 80% of cow's milk proteins. The ability of hydrolyzing proteins by bacteria is also different. In this study, the capacity of lactic acid bacteria to hydrolyze casein or β-casein and the IgG/IgE-binding capacity of hydrolysates were evaluated. The intensity of casein and β-casein degradation was analyzed by SDS-PAGE and RP-HPLC. The hydrolysates were tested for their capacity to inhibit IgG and IgE binding by ELISA. The peptides in the hydrolysate were also analyzed by LC-MS/MS. In these strains, Lactobacillus rhamnosus (CICC No. 22175) had the strongest hydrolysis of casein and β-casein. The hydrolysate of Lactobacillus rhamnosus (CICC No. 22175) showed the lowest antigenicity and potential allergenicity. It also hydrolyzed major allergen IgE epitopes and preserved T cell epitopes. Thereore Lactobacillus rhamnosus (CICC No. 22175) could be used for developing hypoallergenic dairy products and the development of tolerance. PRACTICAL APPLICATIONS: By the study, it obtained that a strain of Lactobacillus rhamnosus could effectively degrade casein and reduced the potential allergenicity of casein. At the same time, some major allergic epitopes were hydrolyzed and T cell epitopes were preserved. Therefore, it is very valuable for the application and development of lactic acid bacteria. The hydrolysate can also be used in a new hypoallergenic dairy formula with specific health benefits and promoting oral tolerance.
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Affiliation(s)
- Meijia Huang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China.,School of Food Science and Technology, Nanchang University, Nanchang, China
| | - Xin Li
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China.,School of Food Science and Technology, Nanchang University, Nanchang, China
| | - Yong Wu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China.,Sino-German Joint Research Institute (Jiangxi-OAI), Nanchang University, Nanchang, China
| | - Xuanyi Meng
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China.,Sino-German Joint Research Institute (Jiangxi-OAI), Nanchang University, Nanchang, China
| | - Ping Tong
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China.,School of Food Science and Technology, Nanchang University, Nanchang, China
| | - Juanli Yuan
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China.,School of Pharmacy, Nanchang University, Nanchang, China
| | - Anshu Yang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China.,Sino-German Joint Research Institute (Jiangxi-OAI), Nanchang University, Nanchang, China
| | - Zhihua Wu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China.,Sino-German Joint Research Institute (Jiangxi-OAI), Nanchang University, Nanchang, China
| | - Hongbing Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China.,Sino-German Joint Research Institute (Jiangxi-OAI), Nanchang University, Nanchang, China
| | - Chunhong Xiong
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China.,School of Food Science and Technology, Nanchang University, Nanchang, China
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13
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Urine Metabolomic Profile of Breast- versus Formula-Fed Neonates Using a Synbiotic-Enriched Formula. Int J Mol Sci 2022; 23:ijms231810476. [PMID: 36142388 PMCID: PMC9499619 DOI: 10.3390/ijms231810476] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 09/04/2022] [Accepted: 09/07/2022] [Indexed: 11/16/2022] Open
Abstract
The aim of this study was to compare the urine metabolic fingerprint of healthy neonates exclusively breastfed with that of neonates fed with a synbiotic-enriched formula (Rontamil® Complete 1) at four time points (the 3rd and 15th days of life and the 2nd and 3rd months). The determination of urine metabolic fingerprint was performed using NMR metabolomics. Multivariate data analyses were performed with SIMCA-P 15.0 software and R language. Non-distinct profiles for both groups (breastfeeding and synbiotic formula) for the two first time points (3rd and 15th days of life) were detected, whereas after the 2nd month of life, a discrimination trend was observed between the two groups, which was further confirmed at the 3rd month of life. A clear discrimination of the synbiotic formula samples was evident when comparing the metabolites taken in the first days of life (3rd day) with those taken in the 2nd and 3rd months of life. In both cases, OPLS-DA models explained more than 75% of the metabolic variance. Non-distinct metabolomic profiles were obtained between breastfed and synbiotic-formula-fed neonates up to the 15th day of life. Discrimination trends were observed only after the 2nd month of the study, which could be attributed to breastfeeding variations and the consequent dynamic profile of urine metabolites compared to the stable ingredients of the synbiotic formula.
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Goh A, Muhardi L, Ali A, Liew WK, Estrada-Reyes E, Zepeda-Ortega B, Kudla U, van Neerven RJJ, Ulfman LH, Lambers TT, Warner JO. Differences between peptide profiles of extensive hydrolysates and their influence on functionality for the management of cow's milk allergy: A short review. FRONTIERS IN ALLERGY 2022; 3:950609. [PMID: 36660742 PMCID: PMC9843608 DOI: 10.3389/falgy.2022.950609] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 08/05/2022] [Indexed: 01/13/2023] Open
Abstract
Extensively hydrolyzed formulas (eHFs) are recommended for the dietary management of cow's milk protein allergy (CMPA) in non-exclusively breastfed infants. Studies show that peptide profiles differ between eHFs. This short review aims to highlight the variability in peptides and their ability to influence allergenicity and possibly the induction of tolerance by different eHFs. The differences between eHFs are determined by the source of the protein fraction (casein or whey), peptide size-distribution profile and residual β-lactoglobulin which is the most immunogenic and allergenic protein in bovine milk for human infants as it is not present in human breastmilk. These differences occur from the hydrolyzation process which result in variable IgE reactivity against cow's milk allergen epitopes by subjects with CMPA and differences in the Th1, Th2 and pro-inflammatory cytokine responses elicited. They also have different effects on gut barrier integrity. Results suggest that one particular eHF-casein had the least allergenic potential due to its low residual allergenic epitope content and demonstrated the greatest effect on restoring gut barrier integrity by its effects on mucin 5AC, occludin and Zona Occludens-1 in human enterocytes. It also increased the production of the tolerogenic cytokines Il-10 and IFN-γ. In addition, recent studies documented promising effects of optional functional ingredients such as pre-, pro- and synbiotics on the management of cow's milk allergy and induction of tolerance, in part via the induction of the production of short chain fatty acids. This review highlights differences in the residual allergenicity, peptide size distribution, presence of optional functional ingredients and overall functionality of several well-characterized eHFs which can impact the management of CMPA and the ability to induce immune tolerance to cow's milk protein.
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Affiliation(s)
- Anne Goh
- Department of Paediatrics, KK Women’s and Children’s Hospital, Singapore, Singapore,Correspondence: Anne Goh
| | - Leilani Muhardi
- Medical Affairs, Friesland Campina AMEA, Singapore, Singapore
| | - Adli Ali
- Department of Paediatrics, Universiti Kebangsaan Malaysia Medical Center, Bangi, Malaysia
| | - Woei Kang Liew
- Paediatric Allergy Immunology Rheumatology Centre, Mount Elizabeth Novena Specialist Centre, Singapore, Singapore
| | | | - Benjamin Zepeda-Ortega
- Department of Pediatrics, Angeles Lomas Hospital Huixquilucan Mexican State, Mexico, Mexico
| | | | - R. J. Joost van Neerven
- R&D, FrieslandCampina, Amersfoort, the Netherlands,Cell Biology and Immunology, Wageningen University, Wageningen, the Netherlands
| | | | | | - John O. Warner
- National Heart and Lung Institute, Imperial College, London, United Kingdom,Departement Pediatrics and Child Health, University of Cape Town, Cape Town, South Africa
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15
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Keulers L, Dehghani A, Knippels L, Garssen J, Papadopoulos N, Folkerts G, Braber S, van Bergenhenegouwen J. Probiotics, prebiotics, and synbiotics to prevent or combat air pollution consequences: The gut-lung axis. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2022; 302:119066. [PMID: 35240267 DOI: 10.1016/j.envpol.2022.119066] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 02/24/2022] [Accepted: 02/25/2022] [Indexed: 05/26/2023]
Abstract
Air pollution exposure is a public health emergency, which attributes globally to an estimated seven million deaths on a yearly basis We are all exposed to air pollutants, varying from ambient air pollution hanging over cities to dust inside the home. It is a mixture of airborne particulate matter and gases that can be subdivided into three categories based on particle diameter. The smallest category called PM0.1 is the most abundant. A fraction of the particles included in this category might enter the blood stream spreading to other parts of the body. As air pollutants can enter the body via the lungs and gut, growing evidence links its exposure to gastrointestinal and respiratory impairments and diseases, like asthma, rhinitis, respiratory tract infections, Crohn's disease, ulcerative colitis, and abdominal pain. It has become evident that there exists a crosstalk between the respiratory and gastrointestinal tracts, commonly referred to as the gut-lung axis. Via microbial secretions, metabolites, immune mediators and lipid profiles, these two separate organ systems can influence each other. Well-known immunomodulators and gut health stimulators are probiotics, prebiotics, together called synbiotics. They might combat air pollution-induced systemic inflammation and oxidative stress by optimizing the microbiota composition and microbial metabolites, thereby stimulating anti-inflammatory pathways and strengthening mucosal and epithelial barriers. Although clinical studies investigating the role of probiotics, prebiotics, and synbiotics in an air pollution setting are lacking, these interventions show promising health promoting effects by affecting the gastrointestinal- and respiratory tract. This review summarizes the current data on how air pollution can affect the gut-lung axis and might impact gut and lung health. It will further elaborate on the potential role of probiotics, prebiotics and synbiotics on the gut-lung axis, and gut and lung health.
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Affiliation(s)
- Loret Keulers
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584, CG, Utrecht, the Netherlands; Danone Nutricia Research, Uppsalalaan 12, 3584, CT, Utrecht, the Netherlands.
| | - Ali Dehghani
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584, CG, Utrecht, the Netherlands
| | - Leon Knippels
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584, CG, Utrecht, the Netherlands; Danone Nutricia Research, Uppsalalaan 12, 3584, CT, Utrecht, the Netherlands
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584, CG, Utrecht, the Netherlands; Danone Nutricia Research, Uppsalalaan 12, 3584, CT, Utrecht, the Netherlands
| | - Nikolaos Papadopoulos
- Centre for Paediatrics and Child Health, Institute of Human Development, University of Manchester, Oxford Road M13 9PL, Manchester, United Kingdom
| | - Gert Folkerts
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584, CG, Utrecht, the Netherlands
| | - Saskia Braber
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584, CG, Utrecht, the Netherlands
| | - Jeroen van Bergenhenegouwen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584, CG, Utrecht, the Netherlands; Danone Nutricia Research, Uppsalalaan 12, 3584, CT, Utrecht, the Netherlands
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16
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Ayechu-Muruzabal V, van de Kaa M, Mukherjee R, Garssen J, Stahl B, Pieters RJ, van’t Land B, Kraneveld AD, Willemsen LEM. Modulation of the Epithelial-Immune Cell Crosstalk and Related Galectin Secretion by DP3-5 Galacto-Oligosaccharides and β-3′Galactosyllactose. Biomolecules 2022; 12:biom12030384. [PMID: 35327576 PMCID: PMC8945669 DOI: 10.3390/biom12030384] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/17/2022] [Accepted: 02/25/2022] [Indexed: 01/27/2023] Open
Abstract
Prebiotic galacto-oligosaccharides (GOS) were shown to support mucosal immune development by enhancing regulatory-type Th1 immune polarization induced by synthetic CpG oligodeoxynucleotides (TLR9 agonist mimicking a bacterial DNA trigger). Epithelial-derived galectin-9 was associated with these immunomodulatory effects. We aimed to identify the most active fractions within GOS based on the degree of polymerization (DP), and to study the immunomodulatory capacities of DP3-sized β-3′galactosyllactose (β-3′GL) using a transwell co-culture model of human intestinal epithelial cells (IEC) and activated peripheral blood mononuclear cells (PBMC). IEC were apically exposed to different DP fractions of GOS or β-3′GL in the presence of CpG, and basolaterally co-cultured with αCD3/CD28-activated PBMC, washed, and incubated in fresh medium for IEC-derived galectin analysis. Only DP3-5 in the presence of CpG enhanced galectin-9 secretion. DP3-sized β-3′GL promoted a regulatory-type Th1 response by increasing IFNγ and IL-10 or galectin-9 concentrations as compared to CpG alone. In addition, IEC-derived galectin-3, -4, and -9 secretion was increased by β-3′GL when combined with CpG. Therefore, the GOS DP3-5 and most effectively DP3-sized β-3′GL supported the immunomodulatory properties induced by CpG by enhancing epithelial-derived galectin secretion, which, in turn, could support mucosal immunity.
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Affiliation(s)
- Veronica Ayechu-Muruzabal
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, The Netherlands; (V.A.-M.); (M.v.d.K.); (J.G.); (A.D.K.)
| | - Melanie van de Kaa
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, The Netherlands; (V.A.-M.); (M.v.d.K.); (J.G.); (A.D.K.)
| | - Reshmi Mukherjee
- Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, The Netherlands; (R.M.); (B.S.); (R.J.P.)
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, The Netherlands; (V.A.-M.); (M.v.d.K.); (J.G.); (A.D.K.)
- Danone Nutricia Research, 3584 CT Utrecht, The Netherlands;
| | - Bernd Stahl
- Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, The Netherlands; (R.M.); (B.S.); (R.J.P.)
- Danone Nutricia Research, 3584 CT Utrecht, The Netherlands;
| | - Roland J. Pieters
- Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, The Netherlands; (R.M.); (B.S.); (R.J.P.)
| | - Belinda van’t Land
- Danone Nutricia Research, 3584 CT Utrecht, The Netherlands;
- Center for Translational Immunology, The Wilhelmina Children’s Hospital, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands
| | - Aletta D. Kraneveld
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, The Netherlands; (V.A.-M.); (M.v.d.K.); (J.G.); (A.D.K.)
| | - Linette E. M. Willemsen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, The Netherlands; (V.A.-M.); (M.v.d.K.); (J.G.); (A.D.K.)
- Correspondence:
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Liang X, Wang Z, Yang H, Luo X, Sun J, Yang M, Shi X, Yue X, Zheng Y. Evaluation of allergenicity of cow milk treated with enzymatic hydrolysis through a mouse model of allergy. J Dairy Sci 2022; 105:1039-1050. [PMID: 34955271 DOI: 10.3168/jds.2021-20686] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 10/08/2021] [Indexed: 01/09/2023]
Abstract
Cow milk (CM) allergy is a worldwide concern. Currently, few studies have been performed on the immunoreactivity of CM and fewer still on the antigenicity of CM in vivo and in vitro. In this study, we assessed the potential allergenicity of enzymatically hydrolyzed CM using in vitro ELISA and oral sensitization and challenge of BALB/c mice. Alcalase-, Protamex-, and Flavourzyme-treated CM (all from Novozymes) diminished IgE binding capacity, with greatest reductions of 56.31%, 50.62%, and 56.45%, respectively. Allergic symptoms and levels of total IgG1 were reduced, and allergic inflammation of the lung, jejunum, and spleen was relieved. Moreover, the numbers of CD8+ T and B220+ cells decreased, and the balance of CD4+ T/CD8+ T cells was effectively regulated. These findings suggest that the potential allergenicity of CM was reduced by enzymatic hydrolysis, and our research will lay a solid foundation for developing high-quality hypoallergenic CM products.
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Affiliation(s)
- Xiaona Liang
- College of Food Science, Shenyang Agricultural University, Shenyang 100866, P. R. China
| | - Zongzhou Wang
- College of Food Science, Shenyang Agricultural University, Shenyang 100866, P. R. China
| | - Hui Yang
- College of Food Science, Shenyang Agricultural University, Shenyang 100866, P. R. China
| | - Xue Luo
- College of Food Science, Shenyang Agricultural University, Shenyang 100866, P. R. China
| | - Jing Sun
- College of Food Science, Shenyang Agricultural University, Shenyang 100866, P. R. China
| | - Mei Yang
- College of Food Science, Shenyang Agricultural University, Shenyang 100866, P. R. China
| | - Xinyang Shi
- College of Food Science, Shenyang Agricultural University, Shenyang 100866, P. R. China
| | - Xiqing Yue
- College of Food Science, Shenyang Agricultural University, Shenyang 100866, P. R. China.
| | - Yan Zheng
- College of Food Science, Shenyang Agricultural University, Shenyang 100866, P. R. China.
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Liang X, Yang H, Luo X, Chen N, Ai Z, Xing Y, Huang W, Wang Z, Zheng Y, Yue X. Assessment of the allergenicity and antigenicity potential of enzymatically hydrolyzed cow milk. FOOD BIOSCI 2022. [DOI: 10.1016/j.fbio.2021.101453] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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19
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Szklany K, Engen PA, Naqib A, Green SJ, Keshavarzian A, Lopez Rincon A, Siebrand CJ, Diks MAP, van de Kaa M, Garssen J, Knippels LMJ, Kraneveld AD. Dietary Supplementation throughout Life with Non-Digestible Oligosaccharides and/or n-3 Poly-Unsaturated Fatty Acids in Healthy Mice Modulates the Gut-Immune System-Brain Axis. Nutrients 2021; 14:173. [PMID: 35011046 PMCID: PMC8746884 DOI: 10.3390/nu14010173] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 12/20/2021] [Accepted: 12/24/2021] [Indexed: 12/11/2022] Open
Abstract
The composition and activity of the intestinal microbial community structures can be beneficially modulated by nutritional components such as non-digestible oligosaccharides and omega-3 poly-unsaturated fatty acids (n-3 PUFAs). These components affect immune function, brain development and behaviour. We investigated the additive effect of a dietary combination of scGOS:lcFOS and n-3 PUFAs on caecal content microbial community structures and development of the immune system, brain and behaviour from day of birth to early adulthood in healthy mice. Male BALB/cByJ mice received a control or enriched diet with a combination of scGOS:lcFOS (9:1) and 6% tuna oil (n-3 PUFAs) or individually scGOS:lcFOS (9:1) or 6% tuna oil (n-3 PUFAs). Behaviour, caecal content microbiota composition, short-chain fatty acid levels, brain monoamine levels, enterochromaffin cells and immune parameters in the mesenteric lymph nodes (MLN) and spleen were assessed. Caecal content microbial community structures displayed differences between the control and dietary groups, and between the dietary groups. Compared to control diet, the scGOS:lcFOS and combination diets increased caecal saccharolytic fermentation activity. The diets enhanced the number of enterochromaffin cells. The combination diet had no effects on the immune cells. Although the dietary effect on behaviour was limited, serotonin and serotonin metabolite levels in the amygdala were increased in the combination diet group. The combination and individual interventions affected caecal content microbial profiles, but had limited effects on behaviour and the immune system. No apparent additive effect was observed when scGOS:lcFOS and n-3 PUFAs were combined. The results suggest that scGOS:lcFOS and n-3 PUFAs together create a balance-the best of both in a healthy host.
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Affiliation(s)
- Kirsten Szklany
- Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands; (K.S.); (A.L.R.); (C.J.S.); (M.A.P.D.); (M.v.d.K.); (J.G.); (L.M.J.K.)
| | - Phillip A. Engen
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush Medical College, Rush University Medical Center, Chicago, IL 60602, USA; (P.A.E.); (A.N.); (A.K.)
| | - Ankur Naqib
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush Medical College, Rush University Medical Center, Chicago, IL 60602, USA; (P.A.E.); (A.N.); (A.K.)
| | - Stefan J. Green
- Genomics and Microbiome Core Facility, Rush University Medical Center, Chicago, IL 60602, USA;
| | - Ali Keshavarzian
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush Medical College, Rush University Medical Center, Chicago, IL 60602, USA; (P.A.E.); (A.N.); (A.K.)
- Department of Medicine & Physiology, Rush University Medical Center, Chicago, IL 60602, USA
| | - Alejandro Lopez Rincon
- Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands; (K.S.); (A.L.R.); (C.J.S.); (M.A.P.D.); (M.v.d.K.); (J.G.); (L.M.J.K.)
- Department of Data Science, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands
| | - Cynthia J. Siebrand
- Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands; (K.S.); (A.L.R.); (C.J.S.); (M.A.P.D.); (M.v.d.K.); (J.G.); (L.M.J.K.)
| | - Mara A. P. Diks
- Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands; (K.S.); (A.L.R.); (C.J.S.); (M.A.P.D.); (M.v.d.K.); (J.G.); (L.M.J.K.)
| | - Melanie van de Kaa
- Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands; (K.S.); (A.L.R.); (C.J.S.); (M.A.P.D.); (M.v.d.K.); (J.G.); (L.M.J.K.)
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands; (K.S.); (A.L.R.); (C.J.S.); (M.A.P.D.); (M.v.d.K.); (J.G.); (L.M.J.K.)
- Global Centre of Excellence Immunology, Nutricia Danone Research, 3584 CT Utrecht, The Netherlands
| | - Leon M. J. Knippels
- Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands; (K.S.); (A.L.R.); (C.J.S.); (M.A.P.D.); (M.v.d.K.); (J.G.); (L.M.J.K.)
- Global Centre of Excellence Immunology, Nutricia Danone Research, 3584 CT Utrecht, The Netherlands
| | - Aletta D. Kraneveld
- Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands; (K.S.); (A.L.R.); (C.J.S.); (M.A.P.D.); (M.v.d.K.); (J.G.); (L.M.J.K.)
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20
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Saturio S, Nogacka AM, Alvarado-Jasso GM, Salazar N, de los Reyes-Gavilán CG, Gueimonde M, Arboleya S. Role of Bifidobacteria on Infant Health. Microorganisms 2021; 9:2415. [PMID: 34946017 PMCID: PMC8708449 DOI: 10.3390/microorganisms9122415] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/19/2021] [Accepted: 11/21/2021] [Indexed: 12/19/2022] Open
Abstract
Bifidobacteria are among the predominant microorganisms during infancy, being a dominant microbial group in the healthy breastfed infant and playing a crucial role in newborns and infant development. Not only the levels of the Bifidobacterium genus but also the profile and quantity of the different bifidobacterial species have been demonstrated to be of relevance to infant health. Although no definitive proof is available on the causal association, reduced levels of bifidobacteria are perhaps the most frequently observed alteration of the intestinal microbiota in infant diseases. Moreover, Bifidobacterium strains have been extensively studied by their probiotic attributes. This review compiles the available information about bifidobacterial composition and function since the beginning of life, describing different perinatal factors affecting them, and their implications on different health alterations in infancy. In addition, this review gathers exhaustive information about pre-clinical and clinical studies with Bifidobacterium strains as probiotics in neonates.
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Affiliation(s)
- Silvia Saturio
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (G.M.A.-J.); (N.S.); (C.G.d.l.R.-G.)
- Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), 33011 Oviedo, Spain
| | - Alicja M. Nogacka
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (G.M.A.-J.); (N.S.); (C.G.d.l.R.-G.)
- Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), 33011 Oviedo, Spain
| | - Guadalupe M. Alvarado-Jasso
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (G.M.A.-J.); (N.S.); (C.G.d.l.R.-G.)
| | - Nuria Salazar
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (G.M.A.-J.); (N.S.); (C.G.d.l.R.-G.)
- Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), 33011 Oviedo, Spain
| | - Clara G. de los Reyes-Gavilán
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (G.M.A.-J.); (N.S.); (C.G.d.l.R.-G.)
- Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), 33011 Oviedo, Spain
| | - Miguel Gueimonde
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (G.M.A.-J.); (N.S.); (C.G.d.l.R.-G.)
- Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), 33011 Oviedo, Spain
| | - Silvia Arboleya
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (G.M.A.-J.); (N.S.); (C.G.d.l.R.-G.)
- Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), 33011 Oviedo, Spain
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21
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Jiang S, Hou Y, Meng L, Pu X, Zhu X, Tuo Y, Qian F, Mu G. Effect of Lactiplantibacillus plantarum HM-22 on immunoregulation and intestinal microbiota in α-lactalbumin-induced allergic mice. Food Funct 2021; 12:8887-8898. [PMID: 34606539 DOI: 10.1039/d1fo01703a] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Milk protein is one of the eight major allergens, and α-lactalbumin (α-LA) is one of the major allergens of bovine milk protein. Our previous studies found that Lactiplantibacillus plantarum HM-22 (L. plantarum HM-22) showed a good gastrointestinal survival rate and intestinal colonization. To investigate the effect of L. plantarum HM-22 on intestinal inflammation and intestinal microbiota in α-LA-induced allergic mice, in this study, L. plantarum HM-22 at low and high doses was intragastrically administered to α-LA-induced allergic mice for 5 weeks. The results showed that L. plantarum HM-22 significantly relieved the weight loss and organ index of α-LA-induced allergic mice (p < 0.05). L. plantarum HM-22 increased the levels of interleukin-10 (IL-10), interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) in the serum of α-LA-induced allergic mice and decreased the levels of total immunoglobulin E (IgE) and the proinflammatory factor interleukin-4 (IL-4) (p < 0.05). The crypt structure of the colon tissues of α-LA-induced allergic mice changed, goblet cells decreased, and the phenomenon of a large number of inflammatory corpuscles that appeared was improved and alleviated with the intervention of L. plantarum HM-22 by hematoxylin-eosin (HE) staining. Western blot analysis showed that L. plantarum HM-22 significantly increased the expression of occludin and claudin-1 in the colon of α-LA-induced allergic mice and decreased the expression of the inflammatory proteins p65 and IκBα (p < 0.05). The intestinal microbiota of mice in each group was determined by 16S rRNA amplicon sequencing, and the results showed that intervention with L. plantarum HM-22 improved the intestinal microbes of α-LA-induced allergic mice. Spearman's correlation analysis revealed the correlation between intestinal microbiota changes and the α-LA-induced allergy-related index. This study provides a theoretical basis for probiotics to prevent allergies by changing the intestinal microbiota.
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Affiliation(s)
- Shujuan Jiang
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, China.
| | - Yaqi Hou
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, China.
| | - Lingying Meng
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, China.
| | - Xueli Pu
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, China.
| | - Xuemei Zhu
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, China.
| | - Yanfeng Tuo
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, China.
| | - Fang Qian
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, China.
| | - Guangqing Mu
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, China.
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22
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Bioactive Compounds in Food as a Current Therapeutic Approach to Maintain a Healthy Intestinal Epithelium. Microorganisms 2021; 9:microorganisms9081634. [PMID: 34442713 PMCID: PMC8401766 DOI: 10.3390/microorganisms9081634] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 07/08/2021] [Accepted: 07/28/2021] [Indexed: 12/12/2022] Open
Abstract
The intestinal epithelium serves as an effective barrier against the external environment, hampering the passage of potentially harmful substances (such as pathogenic microbes) that could trigger an exacerbated host immune response. The integrity of this barrier is thus essential for the maintenance of proper intestinal homeostasis and efficient protective reactions against chemical and microbial challenges. The principal consequence of intestinal barrier defects is an increase in intestinal permeability, which leads to an increased influx of luminal stressors, such as pathogens, toxins, and allergens, which in turn trigger inflammation and immune response. The fine and fragile balance of intestinal homeostasis can be altered by multiple factors that regulate barrier function, many of which are poorly understood. This review will address the role of gut microbiota as well as food supplements (such as probiotics, prebiotics, and synbiotics) in modulating gut health and regulating intestinal barrier function. In particular, we will focus on three human pathologies: inflammatory bowel disease, irritable bowel syndrome, and food allergy.
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23
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Szklany K, Kraneveld AD, Tiemessen MM, Garssen J, Knippels LMJ. Nutritional Interventions to Prevent the Development of Atopic Diseases: A Focus on Cow's Milk Allergy. Handb Exp Pharmacol 2021; 268:471-486. [PMID: 34085122 DOI: 10.1007/164_2021_480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
In the western world the prevalence of atopic diseases such as food allergies is increasing highly significantly. One of the earliest and most prevalent food allergies occurring in the first year of life is cow's milk allergy. No treatment is available and only avoidance of the cow's milk allergens prevents the occurrence of an allergic reaction. Since cow's milk allergic children have an increased risk of developing other allergies later in life, investigating nutritional strategies to prevent the development of cow's milk allergy by developing oral tolerance is of high interest. Nutritional components such as prebiotics, probiotics, synbiotics and long-chain polyunsaturated fatty acids possess potential to support the maturation of the immune system early in life that might prevent the development of cow's milk allergy. The available research, so far, shows promising results particularly on the development of eczema. However, the preventive effects of the nutritional interventions on the development of food allergy are inconclusive. Future research may benefit from the combination of various dietary components. To clarify the preventive effects of the nutritional components in food allergy more randomized clinical trials are needed.
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Affiliation(s)
- Kirsten Szklany
- Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of science, Utrecht University, Utrecht, The Netherlands
| | - Aletta D Kraneveld
- Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of science, Utrecht University, Utrecht, The Netherlands.,Veterinary Pharmacology and Therapeutics, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
| | - Machteld M Tiemessen
- Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of science, Utrecht University, Utrecht, The Netherlands.,Department of Immunology, Danone Nutricia Research, Utrecht, The Netherlands
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of science, Utrecht University, Utrecht, The Netherlands.,Department of Immunology, Danone Nutricia Research, Utrecht, The Netherlands
| | - Leon M J Knippels
- Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of science, Utrecht University, Utrecht, The Netherlands. .,Department of Immunology, Danone Nutricia Research, Utrecht, The Netherlands.
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24
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A Fermented Milk Matrix Containing Postbiotics Supports Th1- and Th17-Type Immunity In Vitro and Modulates the Influenza-Specific Vaccination Response In Vivo in Association with Altered Serum Galectin Ratios. Vaccines (Basel) 2021; 9:vaccines9030254. [PMID: 33805597 PMCID: PMC7998404 DOI: 10.3390/vaccines9030254] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 03/03/2021] [Accepted: 03/11/2021] [Indexed: 12/12/2022] Open
Abstract
During a specific milk fermentation process with Bifidobacterium breve C50 and Streptococcus thermophilus 065 (LactofidusTM), postbiotics with possible immunomodulatory properties are produced. We investigated the effects of this fermentation product (FP) in vitro using a model that allows crosstalk between intestinal epithelial (IEC) and immune cells. IECs were exposed to FP and αCD3/CD28-activated peripheral blood mononuclear cells after which the mediator secretion was measured. Additionally, using a murine influenza vaccination model, immune development was assessed. Mice were fed an AIN93G diet containing FP or lactose as control. Vaccine-specific immunity was measured as delayed-type hypersensitivity (DTH) and correlated to intestinal and systemic immunomodulation levels. In vitro, exposure to FP enhanced IFNγ, TNFα and IL-17A concentrations. Moreover, IEC-derived galectin-3/galectin-9 and galectin-4/galectin-9 ratios were increased. In vivo, dietary intervention with FP increased vaccine-specific DTH responses as compared to the lactose-receiving group. Although no effects on humoral immunity and vaccine-specific T-cell responses were detected, an enhanced systemic serum galectin-3/galectin-9 and galectin-4/galectin-9 ratio correlated with a shift in RORγ (Th17) mRNA expression over regulatory TGFβ1 in the ileum. This was also positively correlated with the increased DTH response. These results indicate that FP can enhance epithelial galectin-3 and -4 over galectin-9 release, and boost adaptive immunity by promoting Th1- and Th17-type cytokines under inflammatory conditions in vitro. Similar variations in galectin and immune balance were observed in the vaccination model, where FP improved the influenza-specific DTH response.
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25
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Suther C, Moore MD, Beigelman A, Zhou Y. The Gut Microbiome and the Big Eight. Nutrients 2020; 12:nu12123728. [PMID: 33287179 PMCID: PMC7761723 DOI: 10.3390/nu12123728] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 11/28/2020] [Accepted: 12/01/2020] [Indexed: 12/11/2022] Open
Abstract
Food allergies are increasing at an alarming rate, with 6.5% of the general population affected. It has been hypothesized that the increase in allergies stems from the “hygiene hypothesis”. The gut microbiome, a collection of microbiota and their genetic contents from the gastrointestinal tract, has been shown to play a part in the development of food allergies. The Food and Drug Administration requires all regulated food companies to clearly state an inclusion of the major, or “big eight” food allergens on packaging. This review is to provide information on the significant advancements related to the gut microbiome and each of the eight major food allergies individually. Establishment of causal connection between the microbiome and food allergies has uncovered novel mechanisms. New strategies are discussed to prevent future sensitization and reaction through novel treatments involving functional additives and dietary changes that target the microbiome.
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Affiliation(s)
- Cassandra Suther
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA; (C.S.); (M.D.M.)
- Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA
| | - Matthew D. Moore
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA; (C.S.); (M.D.M.)
| | - Avraham Beigelman
- Kipper Institute of Allergy and Immunology, Schneider Children’s Medical Center, Tel Aviv University, Tel Aviv 5891000, Israel;
| | - Yanjiao Zhou
- Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA
- Correspondence: ; Tel.: +1-860-679-6379
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26
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Kerperien J, Veening-Griffioen D, Oja A, Wehkamp T, Jeurink PV, Garssen J, Knippels LMJ, Willemsen LEM. Dietary Vitamin D Supplementation Is Ineffective in Preventing Murine Cow's Milk Allergy, Irrespective of the Presence of Nondigestible Oligosaccharides. Int Arch Allergy Immunol 2020; 181:908-918. [PMID: 32814335 DOI: 10.1159/000509750] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 06/09/2020] [Indexed: 12/23/2022] Open
Abstract
INTRODUCTION Cow's milk allergy (CMA) is one of the most common food allergies especially early in life. A mixture of nondigestible short-chain galacto-oligosaccharides, long-chain fructo-oligosaccharides, and pectin-derived acidic-oligosaccharides (GFA) may reduce allergy development and allergic symptoms in murine CMA. Recently, vitamin D (VitD) has been suggested to have beneficial effects in reducing allergy as well. OBJECTIVE In this study, the immune modulatory effect on allergy prevention using the combination of GFA and VitD was investigated. METHODS Female C3H/HeOuJ mice were fed a control or GFA-containing diet with depleted, standard (1,000 IU/kg), or supplemented (5,000 IU/kg) VitD content for 2 weeks before and during whey sensitization (n = 10-15). Mice were sensitized 5 times intragastrically with PBS as a control, whey as cow's milk allergen, and/or cholera toxin as adjuvant on a weekly interval. One week after the last sensitization, mice were intradermally challenged in both ear pinnae and orally with whey, subsequently the acute allergic skin response and shock symptoms were measured. After 18 h, terminal blood samples, mesenteric lymph nodes, and spleens were collected. Whey-specific immunoglobulin (Ig) E and IgG1 levels were measured by means of ELISA. T cell subsets and dendritic cells (DCs) were studied using flow cytometry. RESULTS Additional VitD supplementation did not lower the allergic symptoms compared to the standard VitD diet. CMA mice fed the GFA diet supplemented with VitD (GFA VitD+) significantly decreased the acute allergic skin response of whey sensitized mice when compared to the CMA mice fed VitD (VitD+) group (p < 0.05). The effect of GFA was not improved by extra VitD supplementation even though the CMA mice fed the GFA VitD+ diet had a significantly increased percentage of CD103+ DCs compared to the VitD+ group (p < 0.05). The VitD-deprived mice showed a high percentage of severe shock and many reached the humane endpoint; therefore, these groups were not further analyzed. CONCLUSIONS High-dose VitD supplementation in mice does not protect against CMA development in the presence or absence of GFA.
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Affiliation(s)
- JoAnn Kerperien
- Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - Désirée Veening-Griffioen
- Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.,Nutricia Research B.V, Utrecht, The Netherlands
| | - Anna Oja
- Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | | | - Prescilla V Jeurink
- Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.,Nutricia Research B.V, Utrecht, The Netherlands
| | - Johan Garssen
- Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.,Nutricia Research B.V, Utrecht, The Netherlands
| | - Leon M J Knippels
- Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.,Nutricia Research B.V, Utrecht, The Netherlands
| | - Linette E M Willemsen
- Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands,
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Prebiotics: Mechanisms and Preventive Effects in Allergy. Nutrients 2019; 11:nu11081841. [PMID: 31398959 PMCID: PMC6722770 DOI: 10.3390/nu11081841] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 07/31/2019] [Accepted: 08/01/2019] [Indexed: 12/13/2022] Open
Abstract
Allergic diseases now affect over 30% of individuals in many communities, particularly young children, underscoring the need for effective prevention strategies in early life. These allergic conditions have been linked to environmental and lifestyle changes driving the dysfunction of three interdependent biological systems: microbiota, epithelial barrier and immune system. While this is multifactorial, dietary changes are of particular interest in the altered establishment and maturation of the microbiome, including the associated profile of metabolites that modulate immune development and barrier function. Prebiotics are non-digestible food ingredients that beneficially influence the health of the host by 1) acting as a fermentable substrate for some specific commensal host bacteria leading to the release of short-chain fatty acids in the gut intestinal tract influencing many molecular and cellular processes; 2) acting directly on several compartments and specifically on different patterns of cells (epithelial and immune cells). Nutrients with prebiotic properties are therefore of central interest in allergy prevention for their potential to promote a more tolerogenic environment through these multiple pathways. Both observational studies and experimental models lend further credence to this hypothesis. In this review, we describe both the mechanisms and the therapeutic evidence from preclinical and clinical studies exploring the role of prebiotics in allergy prevention.
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28
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Combined Exposure of Activated Intestinal Epithelial Cells to Nondigestible Oligosaccharides and CpG-ODN Suppresses Th2-Associated CCL22 Release While Enhancing Galectin-9, TGF β, and Th1 Polarization. Mediators Inflamm 2019; 2019:8456829. [PMID: 31427886 PMCID: PMC6683774 DOI: 10.1155/2019/8456829] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 04/22/2019] [Accepted: 06/08/2019] [Indexed: 12/18/2022] Open
Abstract
Background Short-chain galacto- and long-chain fructo-oligosaccharides (scGOS/lcFOS) and CpG-ODN affect intestinal epithelial cells (IEC). Epithelial IL1α may contribute to allergic sensitization via autocrine mediator release affecting dendritic cells (DC). We studied whether IL1α contributes to Th2-associated mediator release by activated IEC and IEC/DC cocultures and possible modulation by scGOS/lcFOS±CpG-ODN. Methods Solid phase or transwell cultured IEC were preincubated with IL1α and/or IFNγ/TNFα for 6 h. The transwell IEC were also apically exposed to scGOS/lcFOS±CpG-ODN for 6 h, washed, and re-exposed, while cocultured with immature moDC (ccDC) for 48 h. These ccDC were subsequently added to allogeneic naïve T cells (MLR). IEC- and/or DC-derived mediators and T cell cytokines were measured. Results IL1α tended to enhance IL25 and enhanced IL33 and CCL20 release by IEC, while IL1α or TNFα or IFNγ enhanced CCL22. These were all further increased upon combined exposure of IFNγ/TNFα±IL1α coinciding with increased IL33 secretion in the solid phase culture. In the transwell, IL25 and IL33 remained under detection, while CCL20 and CCL22 were induced by IL1α or IFNγ/TNFα, respectively, and a synergistic increase was observed upon combined exposure of IFNγ/TNFα and IL1α. Furthermore, IFNγ was found to enhance galectin-9 secretion, which was more pronounced in IFNγ/TNFα±IL1α-exposed IEC and coincided with TGFβ increase. Epithelial CpG-ODN exposure further increased CCL20, while reducing CCL22 release by IFNγ/TNFα/IL1α-activated IEC; however, scGOS/lcFOS suppressed both. Combined scGOS/lcFOS and CpG-ODN reduced CCL22, while CCL20 and regulatory galectin-9 and TGFβ remained high in the supernatant of IFNγ/TNFα/IL1α-activated IEC and the following IEC/DC coculture. ccDC of scGOS/lcFOS- and CpG-ODN-exposed IFNγ/TNFα/IL1α-activated IEC increased IFNγ, IL10, TGFβ, and galectin-9 secretion in the MLR compared to ccDC exposed to control-activated IEC. Conclusion IL1α enhanced CCL20 and Th2-associated CCL22 release by IFNγ/TNFα-activated IEC. Combined scGOS/lcFOS and CpG-ODN exposure suppressed CCL22, while maintaining high CCL20, TGFβ, and galectin-9 concentrations. In addition, ccDC derived from this IEC/DC coculture enhanced Th1 and regulatory mediator secretion mimicking known in vivo effects.
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Wong CB, Iwabuchi N, Xiao JZ. Exploring the Science behind Bifidobacterium breve M-16V in Infant Health. Nutrients 2019; 11:nu11081724. [PMID: 31349739 PMCID: PMC6723912 DOI: 10.3390/nu11081724] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 07/22/2019] [Accepted: 07/24/2019] [Indexed: 12/18/2022] Open
Abstract
Probiotics intervention has been proposed as a feasible preventative approach against adverse health-related complications in infants. Nevertheless, the umbrella concept of probiotics has led to a massive application of probiotics in a range of products for promoting infant health, for which the strain-specificity, safety and efficacy findings associated with a specific probiotics strain are not clearly defined. Bifidobacterium breve M-16V is a commonly used probiotic strain in infants. M-16V has been demonstrated to offer potential in protecting infants from developing the devastating necrotising enterocolitis (NEC) and allergic diseases. This review comprehends the potential beneficial effects of M-16V on infant health particularly in the prevention and treatment of premature birth complications and immune-mediated disorders in infants. Mechanistic studies supporting the use of M-16V implicated that M-16V is capable of promoting early gut microbial colonisation and may be involved in the regulation of immune balance and inflammatory response to protect high-risk infants from NEC and allergies. Summarised information on M-16V has provided conceptual proof of the use of M-16V as a potential probiotics candidate aimed at promoting infant health, particularly in the vulnerable preterm population.
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MESH Headings
- Animals
- Animals, Newborn
- Bifidobacterium breve/physiology
- Disease Models, Animal
- Gastrointestinal Microbiome
- Gestational Age
- Humans
- Infant
- Infant Health
- Infant, Newborn
- Infant, Newborn, Diseases/diagnosis
- Infant, Newborn, Diseases/microbiology
- Infant, Newborn, Diseases/prevention & control
- Infant, Premature
- Probiotics/adverse effects
- Probiotics/therapeutic use
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Affiliation(s)
- Chyn Boon Wong
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa 252-8583, Japan
| | - Noriyuki Iwabuchi
- Food Ingredients and Technology Institute, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa 252-8583, Japan
| | - Jin-Zhong Xiao
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa 252-8583, Japan.
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Rogier R, Ederveen THA, Wopereis H, Hartog A, Boekhorst J, van Hijum SAFT, Knol J, Garssen J, Walgreen B, Helsen MM, van der Kraan PM, van Lent PLEM, van de Loo FAJ, Abdollahi-Roodsaz S, Koenders MI. Supplementation of diet with non-digestible oligosaccharides alters the intestinal microbiota, but not arthritis development, in IL-1 receptor antagonist deficient mice. PLoS One 2019; 14:e0219366. [PMID: 31283798 PMCID: PMC6613703 DOI: 10.1371/journal.pone.0219366] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 06/22/2019] [Indexed: 02/07/2023] Open
Abstract
The intestinal microbiome is perturbed in patients with new-onset and chronic autoimmune inflammatory arthritis. Recent studies in mouse models suggest that development and progression of autoimmune arthritis is highly affected by the intestinal microbiome. This makes modulation of the intestinal microbiota an interesting novel approach to suppress inflammatory arthritis. Prebiotics, defined as non-digestible carbohydrates that selectively stimulate the growth and activity of beneficial microorganisms, provide a relatively non-invasive approach to modulate the intestinal microbiota. The aim of this study was to assess the therapeutic potential of dietary supplementation with a prebiotic mixture of 90% short-chain galacto-oligosaccharides and 10% long-chain fructo-oligosaccharides (scGOS/lcFOS) in experimental arthritis in mice. We here show that dietary supplementation with scGOS/lcFOS has a pronounced effect on the composition of the fecal microbiota. Interestingly, the genera Enterococcus and Clostridium were markedly decreased by scGOS/lcFOS dietary supplementation. In contrast, the family Lachnospiraceae and the genus Lactobacillus, both associated with healthy microbiota, increased in mice receiving scGOS/lcFOS diet. However, the scGOS/lcFOS induced alterations of the intestinal microbiota did not induce significant effects on the intestinal and systemic T helper cell subsets and were not sufficient to reproducibly suppress arthritis in mice. As expected, we did observe a significant increase in the bone mineral density in mice upon dietary supplementation with scGOS/lcFOS for 8 weeks. Altogether, this study suggests that dietary scGOS/lcFOS supplementation is able to promote presumably healthy gut microbiota and improve bone mineral density, but not inflammation, in arthritis-prone mice.
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Affiliation(s)
- Rebecca Rogier
- Experimental Rheumatology, Radboudumc, Nijmegen, The Netherlands
| | - Thomas H. A. Ederveen
- Centre for Molecular and Biomolecular Informatics, Radboudumc, Nijmegen, The Netherlands
| | - Harm Wopereis
- Danone Nutricia Research, Utrecht, The Netherlands
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
| | - Anita Hartog
- Danone Nutricia Research, Utrecht, The Netherlands
- NIZO food research, Ede, The Netherlands
| | - Jos Boekhorst
- Centre for Molecular and Biomolecular Informatics, Radboudumc, Nijmegen, The Netherlands
- NIZO food research, Ede, The Netherlands
| | | | - Jan Knol
- Danone Nutricia Research, Utrecht, The Netherlands
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
| | - Johan Garssen
- Danone Nutricia Research, Utrecht, The Netherlands
- Division of Pharmacology, Utrecht institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
| | | | | | | | | | | | | | - Marije I. Koenders
- Experimental Rheumatology, Radboudumc, Nijmegen, The Netherlands
- * E-mail:
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Abdel-Aziz MI, Vijverberg SJH, Neerincx AH, Kraneveld AD, Maitland-van der Zee AH. The crosstalk between microbiome and asthma: Exploring associations and challenges. Clin Exp Allergy 2019; 49:1067-1086. [PMID: 31148278 PMCID: PMC6852296 DOI: 10.1111/cea.13444] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 05/23/2019] [Accepted: 05/24/2019] [Indexed: 12/17/2022]
Abstract
With the advancement of high‐throughput DNA/RNA sequencing and computational analysis techniques, commensal bacteria are now considered almost as important as pathological ones. Understanding the interaction between these bacterial microbiota, host and asthma is crucial to reveal their role in asthma pathophysiology. Several airway and/or gut microbiome studies have shown associations between certain bacterial taxa and asthma. However, challenges remain before gained knowledge from these studies can be implemented into clinical practice, such as inconsistency between studies in choosing sampling compartments and/or sequencing approaches, variability of results in asthma studies, and not taking into account medication intake and diet composition especially when investigating gut microbiome. Overcoming those challenges will help to better understand the complex asthma disease process. The therapeutic potential of using pro‐ and prebiotics to prevent or reduce risk of asthma exacerbations requires further investigation. This review will focus on methodological issues regarding setting up a microbiome study, recent developments in asthma bacterial microbiome studies, challenges and future therapeutic potential.
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Affiliation(s)
- Mahmoud I Abdel-Aziz
- Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.,Department of Clinical Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt
| | - Susanne J H Vijverberg
- Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Anne H Neerincx
- Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Aletta D Kraneveld
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.,Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
| | - Anke H Maitland-van der Zee
- Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.,Department of Pediatric Respiratory Medicine, Amsterdam UMC, Emma Children's Hospital, Amsterdam, The Netherlands
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Zhao Y, Zhang S, Zhang X, Pan L, Bao N, Qin G. Fructooligosaccharide Inhibits the Absorption of β-conglycinin (A Major Soybean Allergen) in IPEC-J2. INTERNATIONAL JOURNAL OF FOOD ENGINEERING 2019; 15. [DOI: 10.1515/ijfe-2018-0116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Abstract
Dissecting the inhibited variation of allergen absorption could contribute to the development of novel therapeutic or preventive treatments for food/feed allergies. This study investigated the effects of fructooligosaccharide (FOS) on the absorption, intracellular accumulation of intact or hydrolysed β-conglycinin in porcine intestinal epithelial cells (IPEC-J2). As demonstrated by ELISA and immunoblotting, β-conglycinin was absorbed in a dose- and time-dependent manner (p < 0.05). Actually, β-conglycinin was easily transported and absorbed after enzymatic hydrolysis. Three peptides (52 kDa, 30 kDa and 25 kDa) were produced during transcellular absorption of intact or hydrolysed β-conglycinin. FOS inhibited the absorption of β-conglycinin, especially the 52 and 30 kDa peptides. The immunoreactive peptides derived from the 52, 35 or 22 kDa peptides were the substrings of the known epitopes determined by mass spectrometry and bioinformatic analyses. These results indicate that FOS can efficiently inhibit the absorption of 52 and 30 kDa peptides derived from β-conglycinin.
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Affiliation(s)
- Yuan Zhao
- Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Provincial Key Laboratory of Animal nutrition and feed science, College of Animal Science and Technology , Jilin Agricultural University , Changchun 130118 , P.R. China
| | - Shiyao Zhang
- Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Provincial Key Laboratory of Animal nutrition and feed science, College of Animal Science and Technology , Jilin Agricultural University , Changchun 130118 , P.R. China
| | - Xiaodong Zhang
- Institute of Zoonosis, Department of Public Health , Jilin University , Changchun 130062 , P.R. China
| | - Li Pan
- Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Provincial Key Laboratory of Animal nutrition and feed science, College of Animal Science and Technology , Jilin Agricultural University , Changchun 130118 , P.R. China
| | - Nan Bao
- Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Provincial Key Laboratory of Animal nutrition and feed science, College of Animal Science and Technology , Jilin Agricultural University , Changchun 130118 , P.R. China
| | - Guixin Qin
- Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Provincial Key Laboratory of Animal nutrition and feed science, College of Animal Science and Technology , Jilin Agricultural University , Changchun 130118 , P.R. China
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Izumi H, Ehara T, Sugahara H, Matsubara T, Mitsuyama E, Nakazato Y, Tsuda M, Shimizu T, Odamaki T, Xiao JZ, Takeda Y. The Combination of Bifidobacterium breve and Three Prebiotic Oligosaccharides Modifies Gut Immune and Endocrine Functions in Neonatal Mice. J Nutr 2019; 149:344-353. [PMID: 30721975 DOI: 10.1093/jn/nxy248] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 04/03/2018] [Accepted: 09/04/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Several types of oligosaccharides are used in infant formula to improve the gut microbiota of formula-fed infants. We previously reported that a combination of 3 oligosaccharides (lactulose, raffinose, and galacto-oligosaccharides; LRG) and Bifidobacterium breve effectively increased B. breve numbers, acetate, and the expression of several immune- and gut hormone-related mRNAs in neonatal mice gut. OBJECTIVE We investigated whether changes in neonatal gut microbiota alter gut immune and endocrine development. METHODS We first compared postnatal day (PD) 14 with PD21 in C57BL/6J male mouse pups to identify the physiologic immune and endocrine changes during development. In a separate study, we administered phosphate-buffered saline (control group; CON), B. breve M-16V (M-16V), or M-16V + LRG to male mouse pups from PD6 to PD13, and analyzed the gut microbiota and immune and endocrine parameters on PD14 to evaluate whether M-16V + LRG accelerates gut immune and endocrine development. RESULTS The proportion of regulatory T (Treg) cells in the CD4+ cells of large intestinal lamina propria lymphocytes (LPLs) was significantly increased (63% higher) at PD21 compared with PD14. The serum glucagon-like peptide (GLP)-1 tended to be lower (P = 0.0515) and that of GLP-2 was significantly lower (58% lower) at PD21 than at PD14. M-16V + LRG significantly increased the Treg proportion in large intestinal LPL CD4+ cells (20% and 29% higher compared with CON and M-16V, respectively) at PD14. M-16V + LRG also caused significant changes in expression of large intestinal mRNAs that are consistent with developmental progression, and increased serum concentrations of GLP-1 (207% and 311% higher compared with CON and M-16V, respectively) and GLP-2 (57% and 97% higher compared with CON and M-16V, respectively) at PD14. CONCLUSIONS Neonatal administration of M-16V + LRG alters the gut microbiota and enhances gut immune and endocrine development in suckling mice.
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Affiliation(s)
| | - Tatsuya Ehara
- Wellness & Nutrition Science Institute, R&D Division
| | - Hirosuke Sugahara
- Next Generation Science Institute, R&D Division, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
| | | | - Eri Mitsuyama
- Next Generation Science Institute, R&D Division, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
| | - Yuki Nakazato
- Wellness & Nutrition Science Institute, R&D Division
| | - Muneya Tsuda
- Wellness & Nutrition Science Institute, R&D Division
| | | | - Toshitaka Odamaki
- Next Generation Science Institute, R&D Division, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
| | - Jin-Zhong Xiao
- Next Generation Science Institute, R&D Division, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
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Pescuma M, Hébert E, Font G, Saavedra L, Mozzi F. Hydrolysate of β-lactoglobulin by Lactobacillus delbrueckii subsp. bulgaricus CRL 656 suppresses the immunoreactivity of β-lactoglobulin as revealed by in vivo assays. Int Dairy J 2019. [DOI: 10.1016/j.idairyj.2018.08.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Bozzi Cionci N, Baffoni L, Gaggìa F, Di Gioia D. Therapeutic Microbiology: The Role of Bifidobacterium breve as Food Supplement for the Prevention/Treatment of Paediatric Diseases. Nutrients 2018; 10:E1723. [PMID: 30423810 PMCID: PMC6265827 DOI: 10.3390/nu10111723] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 11/05/2018] [Accepted: 11/08/2018] [Indexed: 02/07/2023] Open
Abstract
The human intestinal microbiota, establishing a symbiotic relationship with the host, plays a significant role for human health. It is also well known that a disease status is frequently characterized by a dysbiotic condition of the gut microbiota. A probiotic treatment can represent an alternative therapy for enteric disorders and human pathologies not apparently linked to the gastrointestinal tract. Among bifidobacteria, strains of the species Bifidobacterium breve are widely used in paediatrics. B. breve is the dominant species in the gut of breast-fed infants and it has also been isolated from human milk. It has antimicrobial activity against human pathogens, it does not possess transmissible antibiotic resistance traits, it is not cytotoxic and it has immuno-stimulating abilities. This review describes the applications of B. breve strains mainly for the prevention/treatment of paediatric pathologies. The target pathologies range from widespread gut diseases, including diarrhoea and infant colics, to celiac disease, obesity, allergic and neurological disorders. Moreover, B. breve strains are used for the prevention of side infections in preterm newborns and during antibiotic treatments or chemotherapy. With this documentation, we hope to increase knowledge on this species to boost the interest in the emerging discipline known as "therapeutic microbiology".
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Affiliation(s)
- Nicole Bozzi Cionci
- Department of Agricultural and Food Sciences (DISTAL), Alma Mater Studiorum-Università di Bologna, Viale Fanin 42, 40127 Bologna, Italy.
| | - Loredana Baffoni
- Department of Agricultural and Food Sciences (DISTAL), Alma Mater Studiorum-Università di Bologna, Viale Fanin 42, 40127 Bologna, Italy.
| | - Francesca Gaggìa
- Department of Agricultural and Food Sciences (DISTAL), Alma Mater Studiorum-Università di Bologna, Viale Fanin 42, 40127 Bologna, Italy.
| | - Diana Di Gioia
- Department of Agricultural and Food Sciences (DISTAL), Alma Mater Studiorum-Università di Bologna, Viale Fanin 42, 40127 Bologna, Italy.
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Kerperien J, Veening-Griffioen D, Wehkamp T, van Esch BCAM, Hofman GA, Cornelissen P, Boon L, Jeurink PV, Garssen J, Knippels LMJ, Willemsen LEM. IL-10 Receptor or TGF-β Neutralization Abrogates the Protective Effect of a Specific Nondigestible Oligosaccharide Mixture in Cow-Milk-Allergic Mice. J Nutr 2018; 148:1372-1379. [PMID: 29986071 PMCID: PMC6074790 DOI: 10.1093/jn/nxy104] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Revised: 01/19/2018] [Accepted: 04/20/2018] [Indexed: 11/14/2022] Open
Abstract
Background Dietary nondigestible, short-chain galacto-, long-chain fructo-, and pectin-derived acidic oligosaccharides (GFAs) lower the effector response in cow-milk-allergic (CMA) mice; and forkhead box P3 (Foxp3)-positive regulatory T cells (Tregs) were shown to contribute to this. Objective The aim of this study was to assess the contribution of interleukin 10 (IL-10) and transforming growth factor β (TGF-β) to the protective effect of the GFA diet in CMA mice. Methods Female C3H/HeOuJ mice, 3-4 wk old, were orally sensitized with cholera toxin (Sham) or whey and cholera toxin (Whey) 1 time/wk for 5 consecutive weeks and challenged with whey 1 wk later. The mice were fed a control or 1% GFA (9:2:1) (Whey+GFA) diet starting 2 wk before the first sensitization. In a second experiment, the mice were also injected with αIL-10 receptor (αIL-10r), αTGF-β, or isotype control antibodies 24 h before each sensitization. The acute allergic skin response, anaphylaxis score, whey-specific IgE, mucosal mast cell protease 1 (mMCP-1), and Treg frequency in the mesenteric lymph nodes (MLNs) and intestinal Foxp3, Il10, and Tgfb mRNA expression were determined. Results In Whey+GFA mice, intestinal Il10, Tgfb, or Foxp3 mRNA expression was 2-10 times higher (P < 0.05) and the MLN Treg frequency was 25% higher compared with Whey mice (P < 0.05). The acute allergic skin response was 50% lower in Whey+GFA mice compared with Whey mice (P < 0.01), and IL-10 receptor (IL-10r) or TGF-β neutralizing antibodies prevented this protective effect (P < 0.001). The Whey mice had higher serum mMCP-1 concentrations and whey-immunoglobulin E (-IgE) levels than Sham mice (P < 0.01), whereas these were not higher in Whey+GFA mice, and neutralizing antibodies partially interfered with these responses. Conclusions Dietary GFAs enhance the Treg frequency in the MLNs and mucosal IL-10 and TGF-β transcription while suppressing the allergic effector response. Neutralizing antibodies showed that the allergy-protective effect of the GFA diet was mediated by IL-10 and TGF-β in CMA mice.
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Affiliation(s)
- JoAnn Kerperien
- Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
| | - Désirée Veening-Griffioen
- Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
| | | | - Betty C A M van Esch
- Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
| | - Gerard A Hofman
- Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
| | - Paquita Cornelissen
- Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
| | | | - Prescilla V Jeurink
- Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
| | - Johan Garssen
- Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
| | - Leon M J Knippels
- Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
| | - Linette E M Willemsen
- Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
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Rigo-Adrover MDM, van Limpt K, Knipping K, Garssen J, Knol J, Costabile A, Franch À, Castell M, Pérez-Cano FJ. Preventive Effect of a Synbiotic Combination of Galacto- and Fructooligosaccharides Mixture With Bifidobacterium breve M-16V in a Model of Multiple Rotavirus Infections. Front Immunol 2018; 9:1318. [PMID: 29942312 PMCID: PMC6004411 DOI: 10.3389/fimmu.2018.01318] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Accepted: 05/28/2018] [Indexed: 12/24/2022] Open
Abstract
Rotavirus (RV) causes morbidity and mortality among infants worldwide, and there is evidence that probiotics and prebiotics can have a positive influence against infective processes such as that due to RV. The aim of this study was to evidence a preventive role of one prebiotic mixture (of short-chain galactooligosaccharide/long-chain fructooligosaccharide), the probiotic Bifidobacterium breve M-16V and the combination of the prebiotic and the probiotic, as a synbiotic, in a suckling rat double-RV infection model. Hyperimmune bovine colostrum was used as protection control. The first infection was induced with RV SA11 and the second one with EDIM. Clinical variables and immune response were evaluated after both infections. Dietary interventions ameliorated clinical symptoms after the first infection. The prebiotic and the synbiotic significantly reduced viral shedding after the first infection, but all the interventions showed higher viral load than in the RV group after the second infection. All interventions modulated ex vivo antibody and cytokine production, gut wash cytokine levels and small intestine gene expression after both infections. In conclusion, a daily supplement of the products tested in this preclinical model is highly effective in preventing RV-induced diarrhea but allowing the boost of the early immune response for a future immune response against reinfection, suggesting that these components may be potential agents for modulating RV infection in infants.
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Affiliation(s)
- Maria Del Mar Rigo-Adrover
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, University of Barcelona (UB), Barcelona, Spain.,Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), University of Barcelona (UB), Santa Coloma de Gramanet, Spain
| | | | - Karen Knipping
- Nutricia Research, Utrecht, Netherlands.,Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - Johan Garssen
- Nutricia Research, Utrecht, Netherlands.,Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - Jan Knol
- Nutricia Research, Utrecht, Netherlands
| | - Adele Costabile
- Health Sciences Research Centre, Life Science Department, Whitelands College, University of Roehampton, London, United Kingdom
| | - Àngels Franch
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, University of Barcelona (UB), Barcelona, Spain.,Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), University of Barcelona (UB), Santa Coloma de Gramanet, Spain
| | - Margarida Castell
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, University of Barcelona (UB), Barcelona, Spain.,Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), University of Barcelona (UB), Santa Coloma de Gramanet, Spain
| | - Francisco José Pérez-Cano
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, University of Barcelona (UB), Barcelona, Spain.,Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), University of Barcelona (UB), Santa Coloma de Gramanet, Spain
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Hepatic Mitochondrial Dysfunction and Immune Response in a Murine Model of Peanut Allergy. Nutrients 2018; 10:nu10060744. [PMID: 29890625 PMCID: PMC6024519 DOI: 10.3390/nu10060744] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 06/04/2018] [Accepted: 06/06/2018] [Indexed: 12/24/2022] Open
Abstract
Background: Evidence suggests a relevant role for liver and mitochondrial dysfunction in allergic disease. However, the role of hepatic mitochondrial function in food allergy is largely unknown. We aimed to investigate hepatic mitochondrial dysfunction in a murine model of peanut allergy. Methods: Three-week-old C3H/HeOuJ mice were sensitized by the oral route with peanut-extract (PNT). We investigated: 1. the occurrence of effective sensitization to PNT by analysing acute allergic skin response, anaphylactic symptoms score, body temperature, serum mucosal mast cell protease-1 (mMCP-1) and anti-PNT immunoglobulin E (IgE) levels; 2. hepatic involvement by analysing interleukin (IL)-4, IL-5, IL-13, IL-10 and IFN-γ mRNA expression; 3. hepatic mitochondrial oxidation rates and efficiency by polarography, and hydrogen peroxide (H2O2) yield, aconitase and superoxide dysmutase activities by spectrophotometry. Results: Sensitization to PNT was demonstrated by acute allergic skin response, anaphylactic symptoms score, body temperature decrease, serum mMCP-1 and anti-peanut IgE levels. Liver involvement was demonstrated by a significant increase of hepatic Th2 cytokines (IL-4, IL-5 and IL-13) mRNA expression. Mitochondrial dysfunction was demonstrated by lower state 3 respiration rate in the presence of succinate, decreased fatty acid oxidation in the presence of palmitoyl-carnitine, increased yield of ROS proven by the inactivation of aconitase enzyme and higher H2O2 mitochondrial release. Conclusions: We provide evidence of hepatic mitochondrial dysfunction in a murine model of peanut allergy. These data could open the way to the identification of new mitochondrial targets for innovative preventive and therapeutic strategies against food allergy.
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Candy DCA, Van Ampting MTJ, Oude Nijhuis MM, Wopereis H, Butt AM, Peroni DG, Vandenplas Y, Fox AT, Shah N, West CE, Garssen J, Harthoorn LF, Knol J, Michaelis LJ. A synbiotic-containing amino-acid-based formula improves gut microbiota in non-IgE-mediated allergic infants. Pediatr Res 2018; 83:677-686. [PMID: 29155807 PMCID: PMC6023699 DOI: 10.1038/pr.2017.270] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 10/07/2017] [Indexed: 12/18/2022]
Abstract
BackgroundPrebiotics and probiotics (synbiotics) can modify gut microbiota and have potential in allergy management when combined with amino-acid-based formula (AAF) for infants with cow's milk allergy (CMA).MethodsThis multicenter, double-blind, randomized controlled trial investigated the effects of an AAF-including synbiotic blend on percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group (ER/CC) in feces from infants with suspected non-IgE-mediated CMA. Feces from age-matched healthy breastfed infants were used as reference (healthy breastfed reference (HBR)) for primary outcomes. The CMA subjects were randomized and received test or control formula for 8 weeks. Test formula was a hypoallergenic, nutritionally complete AAF including a prebiotic blend of fructo-oligosaccharides and the probiotic strain Bifidobacterium breve M-16V. Control formula was AAF without synbiotics.ResultsA total of 35 (test) and 36 (control) subjects were randomized; HBR included 51 infants. At week 8, the median percentage of bifidobacteria was higher in the test group than in the control group (35.4% vs. 9.7%, respectively; P<0.001), whereas ER/CC was lower (9.5% vs. 24.2%, respectively; P<0.001). HBR levels of bifidobacteria and ER/CC were 55% and 6.5%, respectively.ConclusionAAF including specific synbiotics, which results in levels of bifidobacteria and ER/CC approximating levels in the HBR group, improves the fecal microbiota of infants with suspected non-IgE-mediated CMA.
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Affiliation(s)
| | | | - Manon M Oude Nijhuis
- Nutricia Research, Nutricia Advanced Medical Nutrition, Utrecht, The Netherlands
| | - Harm Wopereis
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
| | - Assad M Butt
- Royal Alexandra Children’s Hospital, Brighton, UK
| | | | | | - Adam T Fox
- Guy’s and St Thomas’ Hospitals NHS Foundation Trust, London, UK
| | - Neil Shah
- Great Ormond Street Hospital, London, UK
| | | | - Johan Garssen
- Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - Lucien F Harthoorn
- Nutricia Research, Nutricia Advanced Medical Nutrition, Utrecht, The Netherlands
| | - Jan Knol
- Nutricia Research, Nutricia Advanced Medical Nutrition, Utrecht, The Netherlands
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Yang A, Zuo L, Cheng Y, Wu Z, Li X, Tong P, Chen H. Degradation of major allergens and allergenicity reduction of soybean meal through solid-state fermentation with microorganisms. Food Funct 2018; 9:1899-1909. [PMID: 29536997 DOI: 10.1039/c7fo01824j] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
In this study, we determined whether solid-state fermentation could degrade major allergens and reduce potential allergenicity of soybean meal (SBM). Solid-state fermentation was realized through a mixture of Lactobacillus casei, yeast, and Bacillus subtilis. High-performance liquid chromatography, size exclusion-high-performance liquid chromatography, and capillary liquid chromatography/tandem mass spectrometry coupled with electrospray ionization were used to examine the total amino acids and molecular weight distribution of the fermented soybean meal (FSBM). In addition, the potential allergenicity of FSBM was assessed by conducting in vitro competitive inhibition ELISA and oral sensitization and challenge of a BALB/c mice model. The results indicated that the total amino acid content increased and soy protein was degraded into polypeptides with low molecular weights that were derived from the hydrolysis of the allergen sequences N232-D383, G253-I265, E169-S215, G68-G98, A365-I375, and V153-A167. Moreover, the FSBM group exhibited a lower in vitro immunoglobulin E (IgE)-binding capacity than the SBM group. The BALB/c model indicated that the FSBM group manifested milder damage to the intestine, lower mMCP-1 and IgE levels, and higher IFN-γ levels as compared to the SBM group. These findings suggested that the potential allergenicity of SBM was reduced by the solid-state fermentation induced by the mixture of Lactobacillus casei, yeast, and Bacillus subtilis.
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Affiliation(s)
- Anshu Yang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China. and Sino-German Joint Research Institute, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China
| | - LingLing Zuo
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China. and Sino-German Joint Research Institute, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China
| | - Youfei Cheng
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China. and Sino-German Joint Research Institute, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China
| | - Zhihua Wu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China. and Sino-German Joint Research Institute, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China
| | - Xin Li
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China.
| | - Ping Tong
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China.
| | - Hongbing Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China. and Sino-German Joint Research Institute, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China
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Kostadinova AI, Pablos-Tanarro A, Diks MAP, van Esch BCAM, Garssen J, Knippels LMJ, Willemsen LEM. Dietary Intervention with β-Lactoglobulin-Derived Peptides and a Specific Mixture of Fructo-Oligosaccharides and Bifidobacterium breve M-16V Facilitates the Prevention of Whey-Induced Allergy in Mice by Supporting a Tolerance-Prone Immune Environment. Front Immunol 2017; 8:1303. [PMID: 29123515 PMCID: PMC5662887 DOI: 10.3389/fimmu.2017.01303] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Accepted: 09/27/2017] [Indexed: 12/27/2022] Open
Abstract
Cow's milk allergy (CMA) prevails in infants and brings increased risk of developing other allergic diseases. Oral administration of specific β-lactoglobulin (BLG)-derived peptides (PepMix) and a specific blend of short- and long-chain fructo-oligosaccharides and Bifidobacterium breve M-16V (FF/Bb) was found to partially prevent CMA development in mice. In this study, we aimed to expand the knowledge on the preventive potential and the underlying mechanisms of this approach. Three-week-old female C3H/HeOuJ mice were orally exposed to PepMix±FF/Bb prior to a 5-week oral sensitization with whole whey and cholera toxin as an adjuvant. The acute allergic skin response was determined after an intradermal challenge with whole whey protein. Following an oral challenge with whey, regulatory T cells (Tregs) in the small intestine lamina propria (SI-LP) and mRNA expression of immune markers in the Peyer's patches (PP) were investigated. The early impact of PepMix and FF/Bb interventions on the immune system during the oral tolerance (OT) induction phase was investigated after the last OT administration. Pre-exposing mice to PepMix+FF/Bb partially prevented the acute allergic skin response compared to PBS and increased Tregs and activated T cells in the SI-LP compared to sham-sensitized mice. It also increased the mRNA expression of Tbet over GATA3 in the PP of whey-sensitized mice. Directly upon the 6-day OT phase, FF/Bb intervention enhanced cecal content levels of propionic and butyric acid in PepMix-fed mice and the former was positively correlated with Foxp3+ cell numbers in the colon. In the PP of PepMix+FF/Bb-exposed mice, IL-22 mRNA expression increased and IL-10 followed the same tendency, while the Foxp3 expression was increased over GATA3 and RorγT. In the colon, the Tbet mRNA expression increased over GATA3, while IL-22 decreased. In addition, the Foxp3+/GATA3+ and regulatory/effector T cell ratios in the mesenteric lymph nodes and the CD11b+/CD11b- conventional dendritic cells ratio in the SI-LP were increased. In conclusion, the FF/Bb diet facilitates the capacity of the specific BLG-peptides to partially prevent the allergic response after sensitization to whole whey protein, possibly by creating a tolerance-prone environment during the OT phase. Such a dietary intervention might contribute to tailoring successful strategies for CMA prevention.
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Affiliation(s)
- Atanaska I Kostadinova
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.,Department of Immunology, Nutricia Research, Utrecht, Netherlands
| | - Alba Pablos-Tanarro
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.,Instituto de Investigación en Ciencias de la Alimentación (CIAL, CSIC-UAM), Madrid, Spain
| | - Mara A P Diks
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - Betty C A M van Esch
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.,Department of Immunology, Nutricia Research, Utrecht, Netherlands
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.,Department of Immunology, Nutricia Research, Utrecht, Netherlands
| | - Léon M J Knippels
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.,Department of Immunology, Nutricia Research, Utrecht, Netherlands
| | - Linette E M Willemsen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
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Human Milk and Allergic Diseases: An Unsolved Puzzle. Nutrients 2017; 9:nu9080894. [PMID: 28817095 PMCID: PMC5579687 DOI: 10.3390/nu9080894] [Citation(s) in RCA: 89] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Revised: 08/01/2017] [Accepted: 08/01/2017] [Indexed: 02/07/2023] Open
Abstract
There is conflicting evidence on the protective role of breastfeeding in relation to the development of allergic sensitisation and allergic disease. Studies vary in methodology and definition of outcomes, which lead to considerable heterogeneity. Human milk composition varies both within and between individuals, which may partially explain conflicting data. It is known that human milk composition is very complex and contains variable levels of immune active molecules, oligosaccharides, metabolites, vitamins and other nutrients and microbial content. Existing evidence suggests that modulation of human breast milk composition has potential for preventing allergic diseases in early life. In this review, we discuss associations between breastfeeding/human milk composition and allergy development.
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Aitoro R, Simeoli R, Amoroso A, Paparo L, Nocerino R, Pirozzi C, di Costanzo M, Meli R, De Caro C, Picariello G, Mamone G, Calignano A, Nagler CR, Berni Canani R. Extensively hydrolyzed casein formula alone or with L. rhamnosus GG reduces β-lactoglobulin sensitization in mice. Pediatr Allergy Immunol 2017; 28:230-237. [PMID: 27992668 DOI: 10.1111/pai.12687] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/14/2016] [Indexed: 01/04/2023]
Abstract
BACKGROUND Extensively hydrolyzed casein formula (EHCF) has been proposed for the prevention and is commonly used for the treatment of cow's milk allergy (CMA). The addition of the probiotic Lactobacillus rhamnosus GG (LGG) to EHCF may induce faster acquisition of tolerance to cow's milk. The mechanisms underlying this effect are largely unexplored. We investigated the effects of EHCF alone or in combination with LGG on β-lactoglobulin (BLG) sensitization in mice. METHODS Three-week-old C3H/HeOuJ mice were sensitized by oral administration of BLG using cholera toxin as adjuvant at weekly intervals for 5 weeks (sensitization period). Two experimental phases were conducted: (i) EHCF or EHCF+LGG given daily, starting 2 weeks before the sensitization period and then given daily for 5 weeks and (ii) EHCF or EHCF+LGG given daily for 4 weeks, starting 1 week after the sensitization period. Diet free of cow's milk protein was used as control. Acute allergic skin response, anaphylactic symptom score, body temperature, intestinal permeability, anti-BLG serum IgE, and interleukin (IL)-4, IL-5, IL-10, IL-13, IFN-γ mRNA expression were analyzed. Peptide fractions of EHCF were characterized by reversed-phase (RP)-HPLC, MALDI-TOF mass spectrometry, and nano-HPLC/ESI-MS/MS. RESULTS Extensively hydrolyzed casein formula administration before or after BLG-induced sensitization significantly reduced acute allergic skin reaction, anaphylactic symptom score, body temperature decrease, intestinal permeability increase, IL-4, IL-5, IL-13, and anti-BLG IgE production. EHCF increased expression of IFN-γ and IL-10. Many of these effects were significantly enhanced by LGG supplementation. The peptide panels were similar between the two study formulas and contained sequences that could have immunoregulatory activities. CONCLUSIONS The data support dietary intervention with EHCF for CMA prevention and treatment through a favorable immunomodulatory action. The observed effects are significantly enhanced by LGG supplementation.
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Affiliation(s)
- Rosita Aitoro
- Department of Translational Medical Science, University of Naples 'Federico II', Naples, Italy
| | - Raffaele Simeoli
- Department of Pharmacy, University of Naples 'Federico II', Naples, Italy
| | - Antonio Amoroso
- Department of Translational Medical Science, University of Naples 'Federico II', Naples, Italy
| | - Lorella Paparo
- Department of Translational Medical Science, University of Naples 'Federico II', Naples, Italy
| | - Rita Nocerino
- Department of Translational Medical Science, University of Naples 'Federico II', Naples, Italy
| | - Claudio Pirozzi
- Department of Pharmacy, University of Naples 'Federico II', Naples, Italy
| | - Margherita di Costanzo
- Department of Translational Medical Science, University of Naples 'Federico II', Naples, Italy
| | - Rosaria Meli
- Department of Pharmacy, University of Naples 'Federico II', Naples, Italy
| | - Carmen De Caro
- Department of Pharmacy, University of Naples 'Federico II', Naples, Italy
| | | | | | - Antonio Calignano
- Department of Pharmacy, University of Naples 'Federico II', Naples, Italy
| | - Cathryn R Nagler
- Committee on Immunology and Departments of Pathology, University of Chicago, Chicago, IL, USA
| | - Roberto Berni Canani
- Department of Translational Medical Science, University of Naples 'Federico II', Naples, Italy.,European Laboratory for The Investigation of Food Induced Diseases, University of Naples 'Federico II', Naples, Italy.,CEINGE Advanced Biotechnologies, University of Naples 'Federico II', Naples, Italy
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Moya-Pérez A, Luczynski P, Renes IB, Wang S, Borre Y, Anthony Ryan C, Knol J, Stanton C, Dinan TG, Cryan JF. Intervention strategies for cesarean section-induced alterations in the microbiota-gut-brain axis. Nutr Rev 2017; 75:225-240. [PMID: 28379454 PMCID: PMC5410982 DOI: 10.1093/nutrit/nuw069] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Microbial colonization of the gastrointestinal tract is an essential process that modulates host physiology and immunity. Recently, researchers have begun to understand how and when these microorganisms colonize the gut and the early-life factors that impact their natural ecological establishment. The vertical transmission of maternal microbes to the offspring is a critical factor for host immune and metabolic development. Increasing evidence also points to a role in the wiring of the gut-brain axis. This process may be altered by various factors such as mode of delivery, gestational age at birth, the use of antibiotics in early life, infant feeding, and hygiene practices. In fact, these early exposures that impact the intestinal microbiota have been associated with the development of diseases such as obesity, type 1 diabetes, asthma, allergies, and even neurodevelopmental disorders. The present review summarizes the impact of cesarean birth on the gut microbiome and the health status of the developing infant and discusses possible preventative and restorative strategies to compensate for early-life microbial perturbations.
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Affiliation(s)
- Angela Moya-Pérez
- A. Moya-Pérez, P. Luczynski, Y. Borre, C.A. Ryan, C. Stanton, T.G. Dinan, and J.F. Cryan are with the APC Microbiome Institute; C.A. Ryan is with the Department of Paediatrics and Child Health; T.G. Dinan is with the Department of Psychiatry and Neurobehavioural Science; and J.F. Cryan is with the Department of Anatomy and Neuroscience; University College Cork, Cork, Ireland. I.B. Renes and J. Knol are with Nutricia Research, Utrecht, the Netherlands. S. Wang is with Nutricia Research, Singapore. J. Knol is with the Laboratory of Microbiology, Wageningen University, Wageningen, the Netherlands. C. Stanton is with the Teagasc Moorepark Food Research Centre, Fermoy, Cork, Ireland
| | - Pauline Luczynski
- A. Moya-Pérez, P. Luczynski, Y. Borre, C.A. Ryan, C. Stanton, T.G. Dinan, and J.F. Cryan are with the APC Microbiome Institute; C.A. Ryan is with the Department of Paediatrics and Child Health; T.G. Dinan is with the Department of Psychiatry and Neurobehavioural Science; and J.F. Cryan is with the Department of Anatomy and Neuroscience; University College Cork, Cork, Ireland. I.B. Renes and J. Knol are with Nutricia Research, Utrecht, the Netherlands. S. Wang is with Nutricia Research, Singapore. J. Knol is with the Laboratory of Microbiology, Wageningen University, Wageningen, the Netherlands. C. Stanton is with the Teagasc Moorepark Food Research Centre, Fermoy, Cork, Ireland
| | - Ingrid B. Renes
- A. Moya-Pérez, P. Luczynski, Y. Borre, C.A. Ryan, C. Stanton, T.G. Dinan, and J.F. Cryan are with the APC Microbiome Institute; C.A. Ryan is with the Department of Paediatrics and Child Health; T.G. Dinan is with the Department of Psychiatry and Neurobehavioural Science; and J.F. Cryan is with the Department of Anatomy and Neuroscience; University College Cork, Cork, Ireland. I.B. Renes and J. Knol are with Nutricia Research, Utrecht, the Netherlands. S. Wang is with Nutricia Research, Singapore. J. Knol is with the Laboratory of Microbiology, Wageningen University, Wageningen, the Netherlands. C. Stanton is with the Teagasc Moorepark Food Research Centre, Fermoy, Cork, Ireland
| | - Shugui Wang
- A. Moya-Pérez, P. Luczynski, Y. Borre, C.A. Ryan, C. Stanton, T.G. Dinan, and J.F. Cryan are with the APC Microbiome Institute; C.A. Ryan is with the Department of Paediatrics and Child Health; T.G. Dinan is with the Department of Psychiatry and Neurobehavioural Science; and J.F. Cryan is with the Department of Anatomy and Neuroscience; University College Cork, Cork, Ireland. I.B. Renes and J. Knol are with Nutricia Research, Utrecht, the Netherlands. S. Wang is with Nutricia Research, Singapore. J. Knol is with the Laboratory of Microbiology, Wageningen University, Wageningen, the Netherlands. C. Stanton is with the Teagasc Moorepark Food Research Centre, Fermoy, Cork, Ireland
| | - Yuliya Borre
- A. Moya-Pérez, P. Luczynski, Y. Borre, C.A. Ryan, C. Stanton, T.G. Dinan, and J.F. Cryan are with the APC Microbiome Institute; C.A. Ryan is with the Department of Paediatrics and Child Health; T.G. Dinan is with the Department of Psychiatry and Neurobehavioural Science; and J.F. Cryan is with the Department of Anatomy and Neuroscience; University College Cork, Cork, Ireland. I.B. Renes and J. Knol are with Nutricia Research, Utrecht, the Netherlands. S. Wang is with Nutricia Research, Singapore. J. Knol is with the Laboratory of Microbiology, Wageningen University, Wageningen, the Netherlands. C. Stanton is with the Teagasc Moorepark Food Research Centre, Fermoy, Cork, Ireland
| | - C. Anthony Ryan
- A. Moya-Pérez, P. Luczynski, Y. Borre, C.A. Ryan, C. Stanton, T.G. Dinan, and J.F. Cryan are with the APC Microbiome Institute; C.A. Ryan is with the Department of Paediatrics and Child Health; T.G. Dinan is with the Department of Psychiatry and Neurobehavioural Science; and J.F. Cryan is with the Department of Anatomy and Neuroscience; University College Cork, Cork, Ireland. I.B. Renes and J. Knol are with Nutricia Research, Utrecht, the Netherlands. S. Wang is with Nutricia Research, Singapore. J. Knol is with the Laboratory of Microbiology, Wageningen University, Wageningen, the Netherlands. C. Stanton is with the Teagasc Moorepark Food Research Centre, Fermoy, Cork, Ireland
| | - Jan Knol
- A. Moya-Pérez, P. Luczynski, Y. Borre, C.A. Ryan, C. Stanton, T.G. Dinan, and J.F. Cryan are with the APC Microbiome Institute; C.A. Ryan is with the Department of Paediatrics and Child Health; T.G. Dinan is with the Department of Psychiatry and Neurobehavioural Science; and J.F. Cryan is with the Department of Anatomy and Neuroscience; University College Cork, Cork, Ireland. I.B. Renes and J. Knol are with Nutricia Research, Utrecht, the Netherlands. S. Wang is with Nutricia Research, Singapore. J. Knol is with the Laboratory of Microbiology, Wageningen University, Wageningen, the Netherlands. C. Stanton is with the Teagasc Moorepark Food Research Centre, Fermoy, Cork, Ireland
| | - Catherine Stanton
- A. Moya-Pérez, P. Luczynski, Y. Borre, C.A. Ryan, C. Stanton, T.G. Dinan, and J.F. Cryan are with the APC Microbiome Institute; C.A. Ryan is with the Department of Paediatrics and Child Health; T.G. Dinan is with the Department of Psychiatry and Neurobehavioural Science; and J.F. Cryan is with the Department of Anatomy and Neuroscience; University College Cork, Cork, Ireland. I.B. Renes and J. Knol are with Nutricia Research, Utrecht, the Netherlands. S. Wang is with Nutricia Research, Singapore. J. Knol is with the Laboratory of Microbiology, Wageningen University, Wageningen, the Netherlands. C. Stanton is with the Teagasc Moorepark Food Research Centre, Fermoy, Cork, Ireland
| | - Timothy G. Dinan
- A. Moya-Pérez, P. Luczynski, Y. Borre, C.A. Ryan, C. Stanton, T.G. Dinan, and J.F. Cryan are with the APC Microbiome Institute; C.A. Ryan is with the Department of Paediatrics and Child Health; T.G. Dinan is with the Department of Psychiatry and Neurobehavioural Science; and J.F. Cryan is with the Department of Anatomy and Neuroscience; University College Cork, Cork, Ireland. I.B. Renes and J. Knol are with Nutricia Research, Utrecht, the Netherlands. S. Wang is with Nutricia Research, Singapore. J. Knol is with the Laboratory of Microbiology, Wageningen University, Wageningen, the Netherlands. C. Stanton is with the Teagasc Moorepark Food Research Centre, Fermoy, Cork, Ireland
| | - John F. Cryan
- A. Moya-Pérez, P. Luczynski, Y. Borre, C.A. Ryan, C. Stanton, T.G. Dinan, and J.F. Cryan are with the APC Microbiome Institute; C.A. Ryan is with the Department of Paediatrics and Child Health; T.G. Dinan is with the Department of Psychiatry and Neurobehavioural Science; and J.F. Cryan is with the Department of Anatomy and Neuroscience; University College Cork, Cork, Ireland. I.B. Renes and J. Knol are with Nutricia Research, Utrecht, the Netherlands. S. Wang is with Nutricia Research, Singapore. J. Knol is with the Laboratory of Microbiology, Wageningen University, Wageningen, the Netherlands. C. Stanton is with the Teagasc Moorepark Food Research Centre, Fermoy, Cork, Ireland
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Liu MY, Yang ZY, Dai WK, Huang JQ, Li YH, Zhang J, Qiu CZ, Wei C, Zhou Q, Sun X, Feng X, Li DF, Wang HP, Zheng YJ. Protective effect of Bifidobacterium infantis CGMCC313-2 on ovalbumin-induced airway asthma and β-lactoglobulin-induced intestinal food allergy mouse models. World J Gastroenterol 2017; 23:2149-2158. [PMID: 28405142 PMCID: PMC5374126 DOI: 10.3748/wjg.v23.i12.2149] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2016] [Revised: 01/17/2017] [Accepted: 02/17/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To determine whether oral administration of Bifidobacterium infantis CGMCC313-2 (B. infantis CGMCC313-2) inhibits allergen-induced airway inflammation and food allergies in a mouse model.
METHODS Ovalbumin (OVA)-induced allergic asthma and β-lactoglobulin-induced food allergy mouse models were used in this study. Following oral administration of B. infantis CGMCC313-2 during or after allergen sensitization, histopathologic changes in the lung and intestine were evaluated by hematoxylin and eosin (HE) staining. In the allergic asthma mouse model, we evaluated the proportion of lung-infiltrating inflammatory cells. OVA-specific IgE and IgG1 levels in serum and cytokine levels in bronchoalveolar lavage fluid (BALF) were also assessed. In the food allergy mouse model, the levels of total IgE and cytokines in serum were measured.
RESULTS Oral administration of B. infantis CGMCC313-2 during or after allergen sensitization suppressed allergic inflammation in lung and intestinal tissues, while the proportion of infiltrating inflammatory cells was significantly decreased in the BALF of allergic asthma mice. Moreover, B. infantis CGMCC313-2 decreased the serum levels of total IgE in food allergy mice, and reductions in IgE and IgG1 were also observed in OVA-induced allergic asthma mice. The expression of interleukin-4 (IL-4) and IL-13 in both serum and BALF was suppressed following the administration of B. infantis CGMCC313-2, while an effect on serum IL-10 levels was not observed.
CONCLUSION B. infantis CGMCC313-2 inhibits the secretion of allergen-induced IgE, IL-4 and IL-13, and attenuates allergic inflammation.
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van Esch BC, Kostadinova AI, Garssen J, Willemsen LE, Knippels LM. A dietary intervention with non-digestible oligosaccharides and partial hydrolysed whey protein prevents the onset of food allergic symptoms in mice. PHARMANUTRITION 2017. [DOI: 10.1016/j.phanu.2016.11.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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Kostadinova AI, Meulenbroek LAPM, van Esch BCAM, Hofman GA, Garssen J, Willemsen LEM, Knippels LMJ. A Specific Mixture of Fructo-Oligosaccharides and Bifidobacterium breve M-16V Facilitates Partial Non-Responsiveness to Whey Protein in Mice Orally Exposed to β-Lactoglobulin-Derived Peptides. Front Immunol 2017; 7:673. [PMID: 28127297 PMCID: PMC5226939 DOI: 10.3389/fimmu.2016.00673] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Accepted: 12/20/2016] [Indexed: 12/27/2022] Open
Abstract
Oral tolerance is a promising approach for allergy prevention in early life, but it strongly depends on allergen exposure and proper immune environment. Small tolerance-inducing peptides and dietary immunomodulatory components may comprise an attractive method for allergy prevention in at-risk infants. This study aimed to investigate whether early oral exposure to β-lactoglobulin-derived peptides (BLG-peptides) and a specific synbiotic mixture of short- and long- chain fructo-oligosaccharides (scFOS/lcFOS, FF) and Bifidobacterium breve (Bb) M-16V (FF/Bb) can prevent cow’s milk allergy (CMA). Three-week-old female C3H/HeOuJ mice were orally exposed to phosphate buffered saline (PBS), whey protein, or a mixture of four synthetic BLG-peptides combined with a FF/Bb-enriched diet prior to intragastric sensitization with whey protein and cholera toxin. To assess the acute allergic skin response and clinical signs of allergy, mice were challenged intradermally with whole whey protein. Serum immunoglobulins were analyzed after a whey protein oral challenge. Cytokine production by allergen-reactivated splenocytes was measured and changes in T cells subsets in the spleen, mesenteric lymph nodes, and intestinal lamina propria were investigated. Pre-exposing mice to a low dosage of BLG-peptides and a FF/Bb-enriched diet prior to whey protein sensitization resulted in a significant reduction of the acute allergic skin response to whey compared to PBS-pretreated mice fed a control diet. Serum immunoglobulins were not affected, but anaphylactic symptom scores remained low and splenocytes were non-responsive in whey-induced cytokine production. In addition, preservation of the Th1/Th2 balance in the small intestine lamina propria was a hallmark of the mechanism underlying the protective effect of the BLG-peptides–FF/Bb intervention. Prior exposure to BLG-peptides and a FF/Bb-enriched diet is a promising approach for protecting the intestinal Th1/Th2 balance and reducing the allergic response to whole whey protein. Therefore, it might have implications for developing successful nutritional strategies for CMA prevention.
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Affiliation(s)
- Atanaska I Kostadinova
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands; Immunology, Nutricia Research, Utrecht, Netherlands
| | | | - Betty C A M van Esch
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands; Immunology, Nutricia Research, Utrecht, Netherlands
| | - Gerard A Hofman
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht , Netherlands
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands; Immunology, Nutricia Research, Utrecht, Netherlands
| | - Linette E M Willemsen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht , Netherlands
| | - Léon M J Knippels
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands; Immunology, Nutricia Research, Utrecht, Netherlands
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Kang MG, Lee HJ, Cho JY, Kim K, Yang SJ, Kim D. Anti-inflammatory effects of sucrose-derived oligosaccharides produced by a constitutive mutant L. mesenteroides B-512FMCM dextransucrase in high fat diet-fed mice. Biochem Biophys Res Commun 2016; 477:350-5. [PMID: 27342664 DOI: 10.1016/j.bbrc.2016.06.102] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 06/20/2016] [Indexed: 01/07/2023]
Abstract
Oligosaccharide (OS) is used as a sugar replacement as well as an ingredient in functional foods because of its beneficial effects, mainly on reducing calorie content and promoting intestinal health. By contrast, the effects of OS on inflammation are less well investigated. The purpose of this study was to investigate the effects of sucrose-derived OS on glucose control and inflammation in high fat (HF) diet-fed mice. Male C57BL6 mice were randomly assigned to six treatment groups (n = 10-14 mice per group): 1) lean control (CON), 2) HF control, 3) HF-low sucrose (LS, 100 mg/kg/day), 4) HF-high sucrose (HS, 1000 mg/kg/day), 5) HF-low OS (LOS, 100 mg/kg/day), and 6) HF-high OS (HOS, 1000 mg/kg/day). PBS (vehicle), sucrose, and OS were administered by stomach gavage. Body weight, food intake, and markers of liver function (activities of aspartate aminotransferase and alanine aminotransferase) were not affected by the treatments. HOS treatment decreased levels of serum glucose, insulin, and homeostasis model assessment-insulin resistance compared with sucrose treatment. However, serum adiponectin levels of the HOS group were higher than those of the sucrose groups. Serum levels of the pro-inflammatory cytokines interleukin-6 (IL-6) and fetuin-A were lower in the HOS group than in the sucrose groups. Hepatic gene expression levels of pro-inflammatory cytokines and related factors (fetuin-A, NF-κB, TLR4, TNF-alpha, and IL-6) were decreased and the levels of insulin signaling-related molecules (sirtuin 1, insulin receptor, and Akt) were increased in HOS-treated mice as compared with sucrose-treated mice. These results demonstrate that OS treatment is effective in improving glucose control and inflammation in high fat diet-fed mice.
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Affiliation(s)
- Min-Gyung Kang
- Division of Food and Nutrition, Chonnam National University, Gwangju, 61186, Republic of Korea
| | - Hee Jae Lee
- Department of Food and Nutrition, Seoul Women's University, Seoul, 01797, Republic of Korea
| | - Jae-Young Cho
- Graduate School of International Agricultural Technology and Institute of Food Industrialization, Institutes of Green Bio Science & Technology, Seoul National University, Gangwon-do, 25354, Republic of Korea
| | - Kanghwa Kim
- Division of Food and Nutrition, Chonnam National University, Gwangju, 61186, Republic of Korea
| | - Soo Jin Yang
- Department of Food and Nutrition, Seoul Women's University, Seoul, 01797, Republic of Korea.
| | - Doman Kim
- Graduate School of International Agricultural Technology and Institute of Food Industrialization, Institutes of Green Bio Science & Technology, Seoul National University, Gangwon-do, 25354, Republic of Korea.
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49
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van Esch BCAM, Abbring S, Diks MAP, Dingjan GM, Harthoorn LF, Vos AP, Garssen J. Post-sensitization administration of non-digestible oligosaccharides and Bifidobacterium breve M-16V reduces allergic symptoms in mice. Immun Inflamm Dis 2016; 4:155-165. [PMID: 27933160 PMCID: PMC4879462 DOI: 10.1002/iid3.101] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2015] [Revised: 01/26/2016] [Accepted: 01/27/2016] [Indexed: 12/16/2022] Open
Abstract
To support dietary management of severe cow's milk allergic infants, a synbiotic mixture of non-digestible oligosaccharides and Bifidobacterium breve M-16V (B. breve) was designed from source materials that are completely cow's milk-free. It was investigated whether this specific synbiotic concept can reduce an established food allergic response in a research model for hen's egg allergy. Mice were orally sensitized once a week for 5 weeks to ovalbumin (OVA) using cholera toxin (CT) as an adjuvant. Non-sensitized mice received CT in PBS only. Sensitized mice were fed a control diet or a diet enriched with short-chain- (scFOS) and long-chain fructo-oligosaccharides (lcFOS), B. breve or scFOSlcFOS + B. breve for 3 weeks starting after the last sensitization. Non-sensitized mice received the control diet. Anaphylactic shock symptoms, acute allergic skin responses and serum specific IgE, mMCP-1 and galectin-9 were measured upon OVA challenge. Activated Th2-, Th1-cells and regulatory T-cells were quantified in spleen and mesenteric lymph nodes (MLN) and cytokine profiles were analyzed. Short chain fatty acids (SCFA) were measured in ceacal samples. The acute allergic skin response was reduced in mice fed the scFOSlcFOS + B. breve diet compared to mice fed any of the other diets. A reduction in mast cell degranulation (mMCP-1) and anaphylactic shock symptoms was also observed in these mice. Unstimulated splenocyte cultures produced increased levels of IL10 and IFNg in mice fed the scFOSlcFOS + B. breve diet. Correspondingly, increased percentages of activated Th1 cells were observed in the spleen. Allergen-specific re-stimulation of splenocytes showed a decrease in IL5 production. In summary; post-sensitization administration of scFOSlcFOS + B. breve was effective in reducing allergic symptoms after allergen challenge. These effects coincided with changes in regulatory and effector T-cell subsets and increases in the SCFA propionic acid. These results suggest immune modulatory benefits of dietary intervention with a unique combination of scFOSlcFOS + B. breve in established food allergy. Whether these effects translate to human applications is subject for ongoing clinical studies.
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Affiliation(s)
- Betty C. A. M. van Esch
- Faculty of ScienceDivison of PharmacologyUtrecht Institute for Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands
- Nutricia ResearchUtrechtThe Netherlands
| | - Suzanne Abbring
- Faculty of ScienceDivison of PharmacologyUtrecht Institute for Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands
| | - Mara A. P. Diks
- Faculty of ScienceDivison of PharmacologyUtrecht Institute for Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands
| | - Gemma M. Dingjan
- Faculty of ScienceDivison of PharmacologyUtrecht Institute for Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands
| | | | - A. Paul Vos
- Faculty of ScienceDivison of PharmacologyUtrecht Institute for Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands
- Nutricia ResearchNutricia Advanced Medical NutritionUtrechtthe Netherlands
| | - Johan Garssen
- Faculty of ScienceDivison of PharmacologyUtrecht Institute for Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands
- Nutricia ResearchUtrechtThe Netherlands
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50
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Rigo-Adrover M, Saldaña-Ruíz S, van Limpt K, Knipping K, Garssen J, Knol J, Franch A, Castell M, Pérez-Cano FJ. A combination of scGOS/lcFOS with Bifidobacterium breve M-16V protects suckling rats from rotavirus gastroenteritis. Eur J Nutr 2016; 56:1657-1670. [PMID: 27112962 DOI: 10.1007/s00394-016-1213-1] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Accepted: 03/31/2016] [Indexed: 12/17/2022]
Abstract
PURPOSE Rotavirus (RV) is the leading cause of severe diarrhoea among infants and young children, and although more standardized studies are needed, there is evidence that probiotics can help to fight against RV and other infectious and intestinal pathologies. On the other hand, the effects of prebiotics have not been properly addressed in the context of an RV infection. The aim of this study was to demonstrate a protective role for a specific scGOS/lcFOS 9:1 prebiotic mixture (PRE) separately, the probiotic Bifidobacterium breve M-16V (PRO) separately and the combination of the prebiotic mixture and the probiotic (synbiotic, SYN) in a suckling rat RV infection model. METHODS The animals received the intervention from the 3rd to the 21st day of life by oral gavage. On day 7, RV was orally administered. Clinical parameters and immune response were evaluated. RESULTS The intervention with the PRO reduced the incidence, severity and duration of the diarrhoea (p < 0.05). The PRE and SYN products improved clinical parameters as well, but a change in stool consistency induced by the PRE intervention hindered the observation of this effect. Both the PRE and the SYN, but not the PRO, significantly reduced viral shedding. All interventions modulated the specific antibody response in serum and intestinal washes at day 14 and 21 of life. CONCLUSIONS A daily supplement of a scGOS/lcFOS 9:1 prebiotic mixture, Bifidobacterium breve M-16V or a combination of both is highly effective in modulating RV-induced diarrhoea in this preclinical model.
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Affiliation(s)
- M Rigo-Adrover
- Department of Physiology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain.,Nutrition and Food Safety Research Institute (INSA), Barcelona, Spain
| | - S Saldaña-Ruíz
- Department of Physiology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain.,Nutrition and Food Safety Research Institute (INSA), Barcelona, Spain
| | | | - K Knipping
- Nutricia Research, Utrecht, The Netherlands.,Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - J Garssen
- Nutricia Research, Utrecht, The Netherlands.,Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - J Knol
- Nutricia Research, Utrecht, The Netherlands
| | - A Franch
- Department of Physiology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain.,Nutrition and Food Safety Research Institute (INSA), Barcelona, Spain
| | - M Castell
- Department of Physiology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain.,Nutrition and Food Safety Research Institute (INSA), Barcelona, Spain
| | - F J Pérez-Cano
- Department of Physiology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain. .,Nutrition and Food Safety Research Institute (INSA), Barcelona, Spain.
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