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Zhang S, Zhang H, Zhang C, Wang G, Shi C, Li Z, Gao F, Cui Y, Li M, Yang G. Composition and evolutionary characterization of the gut microbiota in pigs. Int Microbiol 2024; 27:993-1008. [PMID: 37982990 PMCID: PMC11300507 DOI: 10.1007/s10123-023-00449-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 10/28/2023] [Accepted: 11/10/2023] [Indexed: 11/21/2023]
Abstract
The intestinal microbiota plays significant role in the physiology and functioning of host organisms. However, there is limited knowledge of the composition and evolution of microbiota-host relationships from wild ancestors to modern domesticated species. In this study, the 16S rRNA gene V3-V4 in the intestinal contents of different pig breeds was analyzed and was compared using high-throughput sequencing. This identified 18 323 amplicon sequence variants, of which the Firmicutes and Actinobacteria phyla and Bifidobacterium and Allobaculum genera were most prevalent in wild pigs (WP). In contrast, Proteobacteria and Firmicutes predominated in Chinese Shanxi Black pigs (CSB), while Firmicutes were the most prevalent phylum in Large White pigs (LW) and Iberian pigs (IB), followed by Bacteroidetes in IB and Proteobacteria in LW. At the genus level, Shigella and Lactobacillus were most prevalent in CSB and LW, while Actinobacillus and Sarcina predominated in IB. Differential gene expression together with phylogenetic and functional analyses indicated significant differences in the relative abundance of microbial taxa between different pig breeds. Although many microbial taxa were common to both wild and domestic pigs, significant diversification was observed in bacterial genes that potentially influence host phenotypic traits. Overall, these findings suggested that both the composition and functions of the microbiota were closely associated with domestication and the evolutionary changes in the host. The members of the microbial communities were vertically transmitted in pigs, with evidence of co-evolution of both the hosts and their intestinal microbial communities. These results enhance our understanding and appreciation of the complex interactions between intestinal microbes and hosts and highlight the importance of applying this knowledge in agricultural and microbiological research.
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Affiliation(s)
- Shuhong Zhang
- College of Biology and Food, Shangqiu Normal University, Shangqiu, 476000, China
| | - Huan Zhang
- College of Biology and Food, Shangqiu Normal University, Shangqiu, 476000, China
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, 450002, China
| | - Cheng Zhang
- College of Biology and Food, Shangqiu Normal University, Shangqiu, 476000, China
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, 450002, China
| | - Guan Wang
- College of Biology and Food, Shangqiu Normal University, Shangqiu, 476000, China
| | - Chuanxing Shi
- College of Biology and Food, Shangqiu Normal University, Shangqiu, 476000, China
| | - Zhiqiang Li
- College of Biology and Food, Shangqiu Normal University, Shangqiu, 476000, China
| | - Fengyi Gao
- College of Biology and Food, Shangqiu Normal University, Shangqiu, 476000, China
| | - Yanyan Cui
- College of Biology and Food, Shangqiu Normal University, Shangqiu, 476000, China
| | - Ming Li
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, 450002, China.
| | - Guangli Yang
- College of Biology and Food, Shangqiu Normal University, Shangqiu, 476000, China.
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2
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Romano A, Balestrini L, Della Scala G, Chico L, Bertini A, Cangioli M, Ciapparelli F, Ciardella E, Congestrí C, Dinelli V, Donati F, Ficini M, Giovanetti C, Nannicini F, Pasquali A, Pieraccini A. Effects of a Nutraceutical Multicompound, with Probiotics, Hericium, PEA, and Undaria in Patients with Irritable Bowel Syndrome. J Diet Suppl 2024; 21:451-461. [PMID: 38186311 DOI: 10.1080/19390211.2023.2296106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2024]
Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal condition. Probiotics and other nutraceutical compounds can have specific indications in the context of IBS. A retrospective analysis was conducted on 123 IBS patients in order to evaluate the effects of an oral probiotic-based dietary supplement (Colicron, one cps/day for 4 wk) on stool consistency and pain intensity. Different time points were defined as follows: baseline (T0), 2 wk of treatment (T2), and 4 wk of treatment (T4). Stool consistency was assessed by using the Bristol Stool Scale. Pain intensity was evaluated by the Visual Analogue Scale (VAS). Patients who were initially categorized as normal retained regular bowel movements throughout the study. Both patients with constipation and diarrhea showed an improvement in the Bristol Stool Scale. The score increased from 1.5 ± 0.5 to 3.3 ± 0.7 (p < 0.001) and decreased from 6.5 ± 0.7 to 4.3 ± 0.9 (p < 0.001) at T4, respectively, compared to T0. The VAS score for pain in the pooled IBS patients improved from 6.7 ± 2.2 to 2.8 ± 1.9 at T0 vs T4 (p < 0.001), with a similar trend also observed when patients were categorized based on stool consistency: normal (from 5.2 ± 1.9 to 2.9 ± 1.7), constipation (from 7.5 ± 1.3 to 3.2 ± 2.2), and diarrhea (6.7 ± 2.3 to 2.5 ± 1.9) (p < 0.001). Colicron could be useful in symptom relief, reducing abdominal pain and improving stool consistency of IBS patients. However, further controlled clinical trials are needed to confirm these preliminary findings.
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Affiliation(s)
- Antonio Romano
- Gastroenterology Private Practitioner, GF. Medical Center, Pisa, Italy
| | | | | | - Lucia Chico
- Laboratori Aliveda srl, Crespina Lorenzana, Pisa, Italy
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Motei DE, Beteri B, Hepsomali P, Tzortzis G, Vulevic J, Costabile A. Supplementation with postbiotic from Bifidobacterium Breve BB091109 improves inflammatory status and endocrine function in healthy females: a randomized, double-blind, placebo-controlled, parallel-groups study. Front Microbiol 2023; 14:1273861. [PMID: 38075921 PMCID: PMC10702524 DOI: 10.3389/fmicb.2023.1273861] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 11/08/2023] [Indexed: 01/12/2025] Open
Abstract
This study evaluated the effects of dietary supplementation with a postbiotic extract of Bifidobacterium breve BB091109 on pro-inflammatory cytokines levels and markers of endocrine function. A prospective, double-blind, placebo-controlled, randomized, single-centered, parallel study was conducted on a group of 40-55-year-old females. The study included 30 healthy females, divided into two groups: a supplement (n = 20) and a placebo (n = 10) groups. Blood and saliva samples were collected at baseline (wk0), after 4 weeks (wk 4) and 12 weeks (12wk) of daily supplementation (500 mg), and 4 weeks (wk 16) after termination of supplementation. The levels of fasting CRP, IL-6, IL-10, TNF-α, IFN-γ, DHEA, estradiol, estriol, progesterone, cortisol and human growth hormone were analysed. The results revealed a significant effect of the 90-day supplementation with B. breve postbiotic extract on changes in CRP, IL-6 levels, DHEA, estradiol and estriol. In conclusion, the supplementation with the B. breve postbiotic extract improved endocrine function in females over 40 years old and induced protective changes in inflammatory markers. These findings highlight the potential health benefits of this supplementation in promoting hormonal balance and reducing inflammation in this population.
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Affiliation(s)
- Diana Elena Motei
- School of Life and Health Sciences, University of Roehampton, London, United Kingdom
| | - Beyda Beteri
- School of Life and Health Sciences, University of Roehampton, London, United Kingdom
| | - Piril Hepsomali
- School of Psychology and Clinical Language Sciences, University of Reading, Reading, United Kingdom
| | | | | | - Adele Costabile
- School of Life and Health Sciences, University of Roehampton, London, United Kingdom
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4
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Chen X, Shi Y. Determinants of microbial colonization in the premature gut. Mol Med 2023; 29:90. [PMID: 37407941 DOI: 10.1186/s10020-023-00689-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 06/20/2023] [Indexed: 07/07/2023] Open
Abstract
Abnormal microbial colonization in the gut at an early stage of life affects growth, development, and health, resulting in short- and long-term adverse effects. Microbial colonization patterns of preterm infants differ from those of full-term infants in that preterm babies and their mothers have more complicated prenatal and postnatal medical conditions. Maternal complications, antibiotic exposure, delivery mode, feeding type, and the use of probiotics may significantly shape the gut microbiota of preterm infants at an early stage of life; however, these influences subside with age. Although some factors and processes are difficult to intervene in or avoid, understanding the potential factors and determinants will help in developing timely strategies for a healthy gut microbiota in preterm infants. This review discusses potential determinants of gut microbial colonization in preterm infants and their underlying mechanisms.
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Affiliation(s)
- Xiaoyu Chen
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, 110000, China
| | - Yongyan Shi
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, 110000, China.
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Ojha S, Patil N, Jain M, Kole C, Kaushik P. Probiotics for Neurodegenerative Diseases: A Systemic Review. Microorganisms 2023; 11:microorganisms11041083. [PMID: 37110506 PMCID: PMC10140855 DOI: 10.3390/microorganisms11041083] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/12/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023] Open
Abstract
Neurodegenerative disorders (ND) are a group of conditions that affect the neurons in the brain and spinal cord, leading to their degeneration and eventually causing the loss of function in the affected areas. These disorders can be caused by a range of factors, including genetics, environmental factors, and lifestyle choices. Major pathological signs of these diseases are protein misfolding, proteosomal dysfunction, aggregation, inadequate degradation, oxidative stress, free radical formation, mitochondrial dysfunctions, impaired bioenergetics, DNA damage, fragmentation of Golgi apparatus neurons, disruption of axonal transport, dysfunction of neurotrophins (NTFs), neuroinflammatory or neuroimmune processes, and neurohumoral symptoms. According to recent studies, defects or imbalances in gut microbiota can directly lead to neurological disorders through the gut-brain axis. Probiotics in ND are recommended to prevent cognitive dysfunction, which is a major symptom of these diseases. Many in vivo and clinical trials have revealed that probiotics (Lactobacillus acidophilus, Bifidobacterium bifidum, and Lactobacillus casei, etc.) are effective candidates against the progression of ND. It has been proven that the inflammatory process and oxidative stress can be modulated by modifying the gut microbiota with the help of probiotics. As a result, this study provides an overview of the available data, bacterial variety, gut-brain axis defects, and probiotics' mode of action in averting ND. A literature search on particular sites, including PubMed, Nature, and Springer Link, has identified articles that might be pertinent to this subject. The search contains the following few groups of terms: (1) Neurodegenerative disorders and Probiotics OR (2) Probiotics and Neurodegenerative disorders. The outcomes of this study aid in elucidating the relationship between the effects of probiotics on different neurodegenerative disorders. This systematic review will assist in discovering new treatments in the future, as probiotics are generally safe and cause mild side effects in some cases in the human body.
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Affiliation(s)
- Sandhya Ojha
- Cell & Developmental Biology Laboratory, Centre of Research for Development, Parul University, Vadodara 391760, India
- Department of Life Sciences, Parul Institute of Applied Sciences, Parul University, Vadodara 391760, India
| | - Nil Patil
- Cell & Developmental Biology Laboratory, Centre of Research for Development, Parul University, Vadodara 391760, India
- Department of Life Sciences, Parul Institute of Applied Sciences, Parul University, Vadodara 391760, India
| | - Mukul Jain
- Cell & Developmental Biology Laboratory, Centre of Research for Development, Parul University, Vadodara 391760, India
- Department of Life Sciences, Parul Institute of Applied Sciences, Parul University, Vadodara 391760, India
| | | | - Prashant Kaushik
- Instituto de Conservacióny Mejora de la Agrodiversidad Valenciana, Universitat Politècnica de València, 46022 Valencia, Spain
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Adıgüzel E, Çiçek B, Ünal G, Aydın MF, Barlak-Keti D. Probiotics and prebiotics alleviate behavioral deficits, inflammatory response, and gut dysbiosis in prenatal VPA-induced rodent model of autism. Physiol Behav 2022; 256:113961. [PMID: 36100109 DOI: 10.1016/j.physbeh.2022.113961] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 08/07/2022] [Accepted: 09/09/2022] [Indexed: 11/16/2022]
Abstract
Autism spectrum disorders are neuropsychiatric conditions characterized by social interaction and communication disorders and repetitive stereotypical behaviors. These disorders are also accompanied by an inflammatory status. Bidirectional communication between microbiome, gut, and brain has been discovered as a major mechanism influencing core symptoms and biomarkers of autism. Therefore, the modulation of the gut microbiota in autism has recently attracted interest. In this study, probiotic- and prebiotic-mediated modulation of the gut microbiota was compared in terms of different symptoms and findings in an experimental autism model. Valproic acid (VPA) (500 mg/kg) was administered to Wistar rats (on prenatal day 12.5) to induce autistic-like behaviors. Based on the supply of probiotics and prebiotics, animals were grouped as control (saline), autistic-like (prenatal VPA), probiotic (prenatal VPA + 22.5 × 109 cfu/day probiotic), prebiotic (prenatal VPA + 100 mg/day prebiotic), and combined treatment (prenatal VPA + 22.5 × 109 cfu/day probiotic + 100 mg/day prebiotic). After the treatment process, behavioral tests (social behaviors, anxiety, stereotypical behavior, sensorimotor gating, and behavioral despair) and biochemical analyses (serum and brain tissue) were conducted, and the quantities of some phyla and genera were determined in stool samples. Significant positive effects of probiotic and combined treatments were observed on the sociability, social interaction, and anxiety parameters. In addition, all three treatments had positive effects on stereotypical behavior. However, the treatments did not affect sensorimotor gating deficits and behavioral despair. Further, probiotic treatment reversed the VPA-induced increase and decrease in serum IL-6 and IL-10 levels, respectively. Combined treatment also significantly increased the IL-10 levels. Prenatal VPA exposure decreased 5-hydroxytryptamine (5-HT) levels in the prefrontal cortex of the brain; however, combined treatment reversed this decrease. Prenatal VPA exposure also caused a decrease in Bacteroidetes/Firmicutes ratio in the gut microbiota, while the probiotic treatment significantly increased this ratio. These findings indicate that probiotic- and prebiotic-mediated microbial modulation may represent a new therapeutic approach to alleviate autistic-like symptoms.
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Affiliation(s)
- Emre Adıgüzel
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Karamanoğlu Mehmetbey University, İbrahim Öktem Street, Karaman 70200, Turkey.
| | - Betül Çiçek
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Erciyes University, Kayseri, Turkey.
| | - Gökhan Ünal
- Department of Pharmacology, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey.
| | - Mehmet Fatih Aydın
- Department of Public Health, Faculty of Health Sciences, Karamanoğlu Mehmetbey University, Karaman, Turkey,.
| | - Didem Barlak-Keti
- Department of Medical Biochemistry, Medical School, Erciyes University, Kayseri, Turkey.
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7
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Huang D, Wang P, Chen J, Li Y, Zhu M, Tang Y, Zhou W. Selective targeting of MD2 attenuates intestinal inflammation and prevents neonatal necrotizing enterocolitis by suppressing TLR4 signaling. Front Immunol 2022; 13:995791. [PMID: 36389716 PMCID: PMC9663461 DOI: 10.3389/fimmu.2022.995791] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 10/14/2022] [Indexed: 10/17/2023] Open
Abstract
Neonatal necrotizing enterocolitis (NEC) is an inflammatory disease that occurs in premature infants and has a high mortality rate; however, the mechanisms behind this disease remain unclear. The TLR4 signaling pathway in intestinal epithelial cells, mediated by TLR4, is important for the activation of the inflammatory storm in NEC infants. Myeloid differentiation protein 2 (MD2) is a key auxiliary component of the TLR4 signaling pathway. In this study, MD2 was found to be significantly increased in intestinal tissues of NEC patients at the acute stage. We further confirmed that MD2 was upregulated in NEC rats. MD2 inhibitor (MI) pretreatment reduced the occurrence and severity of NEC in neonatal rats, inhibited the activation of NF-κB and the release of inflammatory molecules (TNF-α and IL-6), and reduced the severity of intestinal injury. MI pretreatment significantly reduced enterocyte apoptosis while also maintaining tight junction proteins, including occludin and claudin-1, and protecting intestinal mucosal permeability in NEC rats. In addition, an NEC in vitro model was established by stimulating IEC-6 enterocytes with LPS. MD2 overexpression in IEC-6 enterocytes significantly activated NF-κB. Further, both MD2 silencing and MI pretreatment inhibited the inflammatory response. Overexpression of MD2 increased damage to the IEC-6 monolayer cell barrier, while both MD2 silencing and MI pretreatment played a protective role. In conclusion, MD2 triggers an inflammatory response through the TLR4 signaling pathway, leading to intestinal mucosal injury in NEC. In addition, MI alleviates inflammation and reduces intestinal mucosal injury caused by the inflammatory response by blocking the TLR4-MD2/NF-κB signaling axis. These results suggest that inhibiting MD2 may be an important way to prevent NEC.
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Affiliation(s)
- Dabin Huang
- Department of Neonatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
- Department of Pediatrics, Guangdong Second Provincial General Hospital, Guangzhou, China
| | - Ping Wang
- Department of Neonatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Juncao Chen
- Department of Neonatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Yanbin Li
- Department of Neonatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Mingwei Zhu
- Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Yaping Tang
- Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Wei Zhou
- Department of Neonatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
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Intestinal ‘Infant-Type’ Bifidobacteria Mediate Immune System Development in the First 1000 Days of Life. Nutrients 2022; 14:nu14071498. [PMID: 35406110 PMCID: PMC9002861 DOI: 10.3390/nu14071498] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/27/2022] [Accepted: 03/31/2022] [Indexed: 01/05/2023] Open
Abstract
Immune system maturation begins early in life, but few studies have examined how early-life gut microbiota colonization educates the neonatal immune system. Bifidobacteria predominate in the intestines of breastfed infants and metabolize human milk oligosaccharides. This glycolytic activity alters the intestinal microenvironment and consequently stimulates immune system maturation at the neonatal stage. However, few studies have provided mechanistic insights into the contribution of ‘infant-type’ Bifidobacterium species, especially via metabolites such as short-chain fatty acids. In this review, we highlight the first 1000 days of life, which provide a window of opportunity for infant-type bifidobacteria to educate the neonatal immune system. Furthermore, we discuss the instrumental role of infant-type bifidobacteria in the education of the neonatal immune system by inducing immune tolerance and suppressing intestinal inflammation, and the potential underlying mechanism of this immune effect in the first 1000 days of life. We also summarize recent research that suggests the administration of infant-type bifidobacteria helps to modify the intestinal microecology and prevent the progress of immune-mediated disorders.
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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: 56] [Impact Index Per Article: 14.0] [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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Kosuge A, Kunisawa K, Arai S, Sugawara Y, Shinohara K, Iida T, Wulaer B, Kawai T, Fujigaki H, Yamamoto Y, Saito K, Nabeshima T, Mouri A. Heat-sterilized Bifidobacterium breve prevents depression-like behavior and interleukin-1β expression in mice exposed to chronic social defeat stress. Brain Behav Immun 2021; 96:200-211. [PMID: 34062230 DOI: 10.1016/j.bbi.2021.05.028] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 05/26/2021] [Accepted: 05/27/2021] [Indexed: 12/12/2022] Open
Abstract
Major depressive disorder (MDD) is a common and serious psychiatric disease that involves brain inflammation. Bifidobacterium breve is commonly used as a probiotic and was shown to improve colitis and allergic diseases by suppressing the inflammatory response. Heat-sterilized B. breve has beneficial effects on inflammation. We hypothesize, therefore, that this probiotic might reduce depression symptoms. We tested this is a mouse model of social defeat stress. C57BL/6J mice exposed to chronic social defeat stress (CSDS) for five consecutive days developed a mild depression-like behavior characterized by a social interaction impairment. CSDS also altered the gut microbiota composition, such as increased abundance of Bacilli, Bacteroidia, Mollicutes, and Verrucomicrobiae classes and decreased Erysipelotrichi class. The prophylactic effect of heat-sterilized B. breve as a functional food ingredient was evaluated on the depression-like behavior in mice. The supplementation started two weeks before and lasted two weeks after the last exposure to CSDS. Two weeks after CSDS, the mice showed deficits in social interaction and increased levels of inflammatory cytokines, including interleukin-1β (IL-1β) in the prefrontal cortex (PFC) and hippocampus (HIP). Heat-sterilized B. breve supplementation significantly prevented social interaction impairment, suppressed IL-1β increase in the PFC and HIP, and modulated the alteration of the gut microbiota composition induced by CSDS. These findings suggest that heat-sterilized B. breve prevents depression-like behavior and IL-1β expression induced by CSDS through modulation of the gut microbiota composition in mice. Therefore, heat-sterilized B. breve used as an ingredient of functional food might prevent MDD.
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Affiliation(s)
- Aika Kosuge
- Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Sciences, Aichi, Japan
| | - Kazuo Kunisawa
- Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Sciences, Aichi, Japan
| | - Satoshi Arai
- Morinaga Milk Industry Co., Ltd., R&D Division, Food Ingredients & Technology Institute, Kanagawa, Japan
| | - Yumika Sugawara
- Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Sciences, Aichi, Japan
| | - Katsuki Shinohara
- Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Sciences, Aichi, Japan
| | - Tsubasa Iida
- Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Sciences, Aichi, Japan
| | - Bolati Wulaer
- Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Science, Aichi, Japan; Department of Disease Control and Prevention, Fujita Health University Graduate School of Health Sciences, Aichi, Japan
| | - Tomoki Kawai
- Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Sciences, Aichi, Japan
| | - Hidetsugu Fujigaki
- Department of Disease Control and Prevention, Fujita Health University Graduate School of Health Sciences, Aichi, Japan
| | - Yasuko Yamamoto
- Department of Disease Control and Prevention, Fujita Health University Graduate School of Health Sciences, Aichi, Japan
| | - Kuniaki Saito
- Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Science, Aichi, Japan; Department of Disease Control and Prevention, Fujita Health University Graduate School of Health Sciences, Aichi, Japan; Japanese Drug Organization of Appropriate Use and Research, Aichi, Japan
| | - Toshitaka Nabeshima
- Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Science, Aichi, Japan; Japanese Drug Organization of Appropriate Use and Research, Aichi, Japan
| | - Akihiro Mouri
- Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Sciences, Aichi, Japan; Japanese Drug Organization of Appropriate Use and Research, Aichi, Japan.
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11
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Al-Sadi R, Dharmaprakash V, Nighot P, Guo S, Nighot M, Do T, Ma TY. Bifidobacterium bifidum Enhances the Intestinal Epithelial Tight Junction Barrier and Protects against Intestinal Inflammation by Targeting the Toll-like Receptor-2 Pathway in an NF-κB-Independent Manner. Int J Mol Sci 2021; 22:8070. [PMID: 34360835 PMCID: PMC8347470 DOI: 10.3390/ijms22158070] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 07/19/2021] [Accepted: 07/23/2021] [Indexed: 02/07/2023] Open
Abstract
Defective intestinal tight junction (TJ) barrier is a hallmark in the pathogenesis of inflammatory bowel disease (IBD). To date, there are no effective therapies that specifically target the intestinal TJ barrier. Among the various probiotic bacteria, Bifidobacterium, is one of the most widely studied to have beneficial effects on the intestinal TJ barrier. The main purpose of this study was to identify Bifidobacterium species that cause a sustained enhancement in the intestinal epithelial TJ barrier and can be used therapeutically to target the intestinal TJ barrier and to protect against or treat intestinal inflammation. Our results showed that Bifidobacterium bifidum caused a marked, sustained enhancement in the intestinal TJ barrier in Caco-2 monolayers. The Bifidobacterium bifidum effect on TJ barrier was strain-specific, and only the strain designated as BB1 caused a maximal enhancement in TJ barrier function. The mechanism of BB1 enhancement of intestinal TJ barrier required live bacterial cell/enterocyte interaction and was mediated by the BB1 attachment to Toll-like receptor-2 (TLR-2) at the apical membrane surface. The BB1 enhancement of the intestinal epithelial TJ barrier function was mediated by the activation of the p38 kinase pathway, but not the NF-κB signaling pathway. Moreover, the BB1 caused a marked enhancement in mouse intestinal TJ barrier in a TLR-2-dependent manner and protected against dextran sodium sulfate (DSS)-induced increase in mouse colonic permeability, and treated the DSS-induced colitis in a TJ barrier-dependent manner. These studies show that probiotic bacteria BB1 causes a strain-specific enhancement of the intestinal TJ barrier through a novel mechanism involving BB1 attachment to the enterocyte TLR-2 receptor complex and activation of p38 kinase pathway.
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Affiliation(s)
| | | | | | | | | | | | - Thomas Y. Ma
- Department of Medicine, Penn State College of Medicine, Hershey Medical Center, Penn State University, Hershey, PA 17033, USA; (R.A.-S.); (V.D.); (P.N.); (S.G.); (M.N.); (T.D.)
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12
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de Lange IH, van Gorp C, Eeftinck Schattenkerk LD, van Gemert WG, Derikx JPM, Wolfs TGAM. Enteral Feeding Interventions in the Prevention of Necrotizing Enterocolitis: A Systematic Review of Experimental and Clinical Studies. Nutrients 2021; 13:1726. [PMID: 34069699 PMCID: PMC8161173 DOI: 10.3390/nu13051726] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 05/14/2021] [Accepted: 05/15/2021] [Indexed: 12/11/2022] Open
Abstract
Necrotizing enterocolitis (NEC), which is characterized by severe intestinal inflammation and in advanced stages necrosis, is a gastrointestinal emergency in the neonate with high mortality and morbidity. Despite advancing medical care, effective prevention strategies remain sparse. Factors contributing to the complex pathogenesis of NEC include immaturity of the intestinal immune defense, barrier function, motility and local circulatory regulation and abnormal microbial colonization. Interestingly, enteral feeding is regarded as an important modifiable factor influencing NEC pathogenesis. Moreover, breast milk, which forms the currently most effective prevention strategy, contains many bioactive components that are known to support neonatal immune development and promote healthy gut colonization. This systematic review describes the effect of different enteral feeding interventions on the prevention of NEC incidence and severity and the effect on pathophysiological mechanisms of NEC, in both experimental NEC models and clinical NEC. Besides, pathophysiological mechanisms involved in human NEC development are briefly described to give context for the findings of altered pathophysiological mechanisms of NEC by enteral feeding interventions.
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Affiliation(s)
- Ilse H. de Lange
- European Surgical Center Aachen/Maastricht, Department of Pediatric Surgery, School for Nutrition, Toxicology and Metabolism (NUTRIM), 6202 AZ Maastricht, The Netherlands; (I.H.d.L.); (W.G.v.G.)
- Department of Surgery, School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University, 6202 AZ Maastricht, The Netherlands
- Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands;
| | - Charlotte van Gorp
- Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands;
| | - Laurens D. Eeftinck Schattenkerk
- Department of Pediatric Surgery, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam and Vrije Universiteit Amsterdam, 1105 AZ Amsterdam, The Netherlands; (L.D.E.S.); (J.P.M.D.)
| | - Wim G. van Gemert
- European Surgical Center Aachen/Maastricht, Department of Pediatric Surgery, School for Nutrition, Toxicology and Metabolism (NUTRIM), 6202 AZ Maastricht, The Netherlands; (I.H.d.L.); (W.G.v.G.)
- Department of Surgery, School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University, 6202 AZ Maastricht, The Netherlands
| | - Joep P. M. Derikx
- Department of Pediatric Surgery, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam and Vrije Universiteit Amsterdam, 1105 AZ Amsterdam, The Netherlands; (L.D.E.S.); (J.P.M.D.)
| | - Tim G. A. M. Wolfs
- Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands;
- Department of Biomedical Engineering (BMT), School for Cardiovascular Diseases (CARIM), Maastricht University, 6202 AZ Maastricht, The Netherlands
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13
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Horigome A, Hisata K, Odamaki T, Iwabuchi N, Xiao JZ, Shimizu T. Colonization of Supplemented Bifidobacterium breve M-16V in Low Birth Weight Infants and Its Effects on Their Gut Microbiota Weeks Post-administration. Front Microbiol 2021; 12:610080. [PMID: 33897631 PMCID: PMC8058467 DOI: 10.3389/fmicb.2021.610080] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 03/17/2021] [Indexed: 12/12/2022] Open
Abstract
The colonization and persistence of probiotics introduced into the adult human gut appears to be limited. It is uncertain, however, whether probiotics can successfully colonize the intestinal tracts of full-term and premature infants. In this study, we investigated the colonization and the effect of oral supplementation with Bifidobacterium breve M-16V on the gut microbiota of low birth weight (LBW) infants. A total of 22 LBW infants (12 infants in the M-16V group and 10 infants in the control group) were enrolled. B. breve M-16V was administrated to LBW infants in the M-16V group from birth until hospital discharge. Fecal samples were collected from each subject at weeks (3.7-9.3 weeks in the M-16V group and 2.1-6.1 weeks in the control group) after discharge. qPCR analysis showed that the administrated strain was detected in 83.3% of fecal samples in the M-16V group (at log10 8.33 ± 0.99 cell numbers per gram of wet feces), suggesting that this strain colonized most of the infants beyond several weeks post-administration. Fecal microbiota analysis by 16S rRNA gene sequencing showed that the abundance of Actinobacteria was significantly higher (P < 0.01), whereas that of Proteobacteria was significantly lower (P < 0.001) in the M-16V group as compared with the control group. Notably, the levels of the administrated strain and indigenous Bifidobacterium bacteria were both significantly higher in the M-16V group than in the control group. Our findings suggest that oral administration of B. breve M-16V led to engraftment for at least several weeks post-administration and we observed a potential overall improvement in microbiota formation in the LBW infants' guts.
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Affiliation(s)
- Ayako Horigome
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
| | - Ken Hisata
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Toshitaka Odamaki
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
| | - Noriyuki Iwabuchi
- Food Ingredients and Technology Institute, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
| | - Jin-Zhong Xiao
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
| | - Toshiaki Shimizu
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
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14
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Hortensius LM, van den Hooven EH, Dudink J, Tataranno ML, van Elburg RM, Benders MJNL. NutriBrain: protocol for a randomised, double-blind, controlled trial to evaluate the effects of a nutritional product on brain integrity in preterm infants. BMC Pediatr 2021; 21:132. [PMID: 33731062 PMCID: PMC7968155 DOI: 10.1186/s12887-021-02570-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Accepted: 02/24/2021] [Indexed: 11/23/2022] Open
Abstract
Background The gut microbiota and the brain are connected through different mechanisms. Bacterial colonisation of the gut plays a substantial role in normal brain development, providing opportunities for nutritional neuroprotective interventions that target the gut microbiome. Preterm infants are at risk for brain injury, especially white matter injury, mediated by inflammation and infection. Probiotics, prebiotics and L-glutamine are nutritional components that have individually already demonstrated beneficial effects in preterm infants, mostly by reducing infections or modulating the inflammatory response. The NutriBrain study aims to evaluate the benefits of a combination of probiotics, prebiotics and L-glutamine on white matter microstructure integrity (i.e., development of white matter tracts) at term equivalent age in very and extremely preterm born infants. Methods This study is a double-blind, randomised, controlled, parallel-group, single-center study. Eighty-eight infants born between 24 + 0 and < 30 + 0 weeks gestational age and less than 72 h old will be randomised after parental informed consent to receive either active study product or placebo. Active study product consists of a combination of Bifidobacterium breve M-16V, short-chain galacto-oligosaccharides, long-chain fructo-oligosaccharides and L-glutamine and will be given enterally in addition to regular infant feeding from 48 to 72 h after birth until 36 weeks postmenstrual age. The primary study outcome of white matter microstructure integrity will be measured as fractional anisotropy, assessed using magnetic resonance diffusion tensor imaging at term equivalent age and analysed using Tract-Based Spatial Statistics. Secondary outcomes are white matter injury, brain tissue volumes and cortical morphology, serious neonatal infections, serum inflammatory markers and neurodevelopmental outcome. Discussion This study will be the first to evaluate the effect of a combination of probiotics, prebiotics and L-glutamine on brain development in preterm infants. It may give new insights in the development and function of the gut microbiota and immune system in relation to brain development and provide a new, safe treatment possibility to improve brain development in the care for preterm infants. Trial registration ISRCTN, ISRCTN96620855. Date assigned: 10/10/2017. Supplementary Information The online version contains supplementary material available at 10.1186/s12887-021-02570-x.
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Affiliation(s)
- Lisa M Hortensius
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.,University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands
| | | | - Jeroen Dudink
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.,University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands
| | - Maria Luisa Tataranno
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.,University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands
| | - Ruurd M van Elburg
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.,Emma Children's Hospital, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Manon J N L Benders
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. .,University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.
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15
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Torres-Castro P, Grases-Pintó B, Abril-Gil M, Castell M, Rodríguez-Lagunas MJ, Pérez-Cano FJ, Franch À. Modulation of the Systemic Immune Response in Suckling Rats by Breast Milk TGF-β2, EGF and FGF21 Supplementation. Nutrients 2020; 12:nu12061888. [PMID: 32599899 PMCID: PMC7353385 DOI: 10.3390/nu12061888] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 06/17/2020] [Accepted: 06/21/2020] [Indexed: 12/17/2022] Open
Abstract
Breast milk is a rich fluid containing bioactive compounds such as specific growth factors (GF) that contribute to maturation of the immune system in early life. The aim of this study was to determine whether transforming growth factor-β2 (TGF-β2), epidermal growth factor (EGF) and fibroblast growth factor 21 (FGF21), compounds present in breast milk, could promote systemic immune maturation. For this purpose, newborn Wistar rats were daily supplemented with these GF by oral gavage during the suckling period (21 days of life). At day 14 and 21 of life, plasma for immunoglobulin (Ig) quantification was obtained and spleen lymphocytes were isolated, immunophenotyped and cultured to evaluate their ability to proliferate and release cytokines. The main result was obtained at day 14, when supplementation with EGF increased B cell proportion to reach levels observed at day 21. At the end of the suckling period, all GF increased the plasma levels of IgG1 and IgG2a isotypes, FGF21 balanced the Th1/Th2 cytokine response and both EGF and FGF21 modified splenic lymphocyte composition. These results suggested that the studied milk bioactive factors, mainly EGF and FGF21, may have modulatory roles in the systemic immune responses in early life, although their physiological roles remain to be established.
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Affiliation(s)
- Paulina Torres-Castro
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain; (P.T.-C.); (B.G.-P.); (M.A.-G.); (M.C.); (M.J.R.-L.); (A.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
| | - Blanca Grases-Pintó
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain; (P.T.-C.); (B.G.-P.); (M.A.-G.); (M.C.); (M.J.R.-L.); (A.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
| | - Mar Abril-Gil
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain; (P.T.-C.); (B.G.-P.); (M.A.-G.); (M.C.); (M.J.R.-L.); (A.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
| | - Margarida Castell
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain; (P.T.-C.); (B.G.-P.); (M.A.-G.); (M.C.); (M.J.R.-L.); (A.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
| | - María J. Rodríguez-Lagunas
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain; (P.T.-C.); (B.G.-P.); (M.A.-G.); (M.C.); (M.J.R.-L.); (A.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
| | - Francisco J. Pérez-Cano
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain; (P.T.-C.); (B.G.-P.); (M.A.-G.); (M.C.); (M.J.R.-L.); (A.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
- Correspondence: ; Tel.: +34-93-402-45-05
| | - Àngels Franch
- Section of Physiology, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain; (P.T.-C.); (B.G.-P.); (M.A.-G.); (M.C.); (M.J.R.-L.); (A.F.)
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain
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16
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Yang G, Shi C, Zhang S, Liu Y, Li Z, Gao F, Cui Y, Yan Y, Li M. Characterization of the bacterial microbiota composition and evolution at different intestinal tract in wild pigs ( Sus scrofa ussuricus). PeerJ 2020; 8:e9124. [PMID: 32518722 PMCID: PMC7258971 DOI: 10.7717/peerj.9124] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Accepted: 04/14/2020] [Indexed: 12/29/2022] Open
Abstract
Commensal microorganisms are essential to the normal development and function of many aspects of animal biology, including digestion, nutrient absorption, immunological development, behaviors, and evolution. The specific microbial composition and evolution of the intestinal tracts of wild pigs remain poorly characterized. This study therefore sought to assess the composition, distribution, and evolution of the intestinal microbiome of wild pigs. For these analyses, 16S rRNA V3-V4 regions from five gut sections prepared from each of three wild sows were sequenced to detect the microbiome composition. These analyses revealed the presence of 6,513 operational taxonomic units (OTUs) mostly distributed across 17 phyla and 163 genera in these samples, with Firmicutes and Actinobacteria being the most prevalent phyla of microbes present in cecum and jejunum samples, respectively. Moreover, the abundance of Actinobacteria in wild pigs was higher than that in domestic pigs. At the genus level the Bifidobacterium and Allobaculum species of microbes were most abundant in all tested gut sections, with higher relative abundance in wild pigs relative to domestic pigs, indicating that in the process of pig evolution, the intestinal microbes also evolved, and changes in the intestinal microbial diversity could have been one of the evolutionary forces of pigs. Intestinal microbial functional analyses also revealed the microbes present in the small intestine (duodenum, jejunum, and ileum) and large intestine (cecum and colon) of wild pigs to engage distinct metabolic spatial structures and pathways relative to one another. Overall, these results offer unique insights that would help to advance the current understanding of how the intestinal microbes interact with the host and affect the evolution of pigs.
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Affiliation(s)
- Guangli Yang
- Department of Biology and Food Sciences, Shangqiu Normal University, Shangqiu City, Henan Province, China
| | - Chuanxin Shi
- Department of Biology and Food Sciences, Shangqiu Normal University, Shangqiu City, Henan Province, China
| | - Shuhong Zhang
- Department of Biology and Food Sciences, Shangqiu Normal University, Shangqiu City, Henan Province, China
| | - Yan Liu
- College of Animal Husbandry Engineering, Henan Vocational College of Agricultural, Zhengzhou City, Henan Province, China
| | - Zhiqiang Li
- Department of Biology and Food Sciences, Shangqiu Normal University, Shangqiu City, Henan Province, China
| | - Fengyi Gao
- Department of Biology and Food Sciences, Shangqiu Normal University, Shangqiu City, Henan Province, China
| | - Yanyan Cui
- Department of Biology and Food Sciences, Shangqiu Normal University, Shangqiu City, Henan Province, China
| | - Yongfeng Yan
- Department of Biology and Food Sciences, Shangqiu Normal University, Shangqiu City, Henan Province, China
| | - Ming Li
- Engineering College of Animal Husbandry and Veterinary Science, Henan Agricultural University, Zhengzhou City, Henan Province, China
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17
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Demers-Mathieu V, Huston RK, Dallas DC. Cytokine Expression by Human Macrophage-Like Cells Derived from the Monocytic Cell Line THP-1 Differs Between Treatment With Milk from Preterm- and Term-Delivering Mothers and Pasteurized Donor Milk. Molecules 2020; 25:molecules25102376. [PMID: 32443898 PMCID: PMC7287623 DOI: 10.3390/molecules25102376] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 05/17/2020] [Accepted: 05/18/2020] [Indexed: 11/25/2022] Open
Abstract
Immunomodulatory proteins from human milk may enhance the protection and development of the infant’s gut. This study compared the immunomodulatory effects of treatment with milk from preterm-(PM) and term-delivering (TM) mothers and pasteurized donor milk (DM) on cytokine gene expression in human macrophage-like cells derived from the monocytic cell line THP-1. The gene expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-12 (p40), IL-10 and GAPDH in macrophages treated with PM, TM and DM at steady and activated (inflammatory) states were measured using real-time reverse transcription-polymerase chain reaction. TNF-α and IL-6 in macrophages (both states) with DM were higher than PM or TM. IL-10 in steady state macrophages with DM was higher than PM whereas DM increased IL-10 in activated macrophages compared with TM. TM increased IL-6 and IL-12 (p40) in steady state macrophages compared with PM. IL-12 (p40) in activated macrophages with TM was higher than PM. IL-10 in steady state macrophages with TM was higher than PM. These results suggest that DM induces higher gene expression of pro-inflammatory and anti-inflammatory cytokines in macrophages compared with PM or TM. PM reduced gene expression of pro-inflammatory cytokines compared with TM, which may decrease the development of necrotizing enterocolitis and systematic inflammation.
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Affiliation(s)
- Veronique Demers-Mathieu
- Nutrition Program, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 97331, USA
- Correspondence: ; Tel.: +1-541-286-8366
| | - Robert K. Huston
- Department of Pediatrics, Randall Children’s Hospital at Legacy Emanuel, Portland, OR 97227, USA; (R.K.H.); (D.C.D.)
| | - David C. Dallas
- Department of Pediatrics, Randall Children’s Hospital at Legacy Emanuel, Portland, OR 97227, USA; (R.K.H.); (D.C.D.)
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18
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Cukrowska B, Bierła JB, Zakrzewska M, Klukowski M, Maciorkowska E. The Relationship between the Infant Gut Microbiota and Allergy. The Role of Bifidobacterium breve and Prebiotic Oligosaccharides in the Activation of Anti-Allergic Mechanisms in Early Life. Nutrients 2020; 12:nu12040946. [PMID: 32235348 PMCID: PMC7230322 DOI: 10.3390/nu12040946] [Citation(s) in RCA: 106] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 03/23/2020] [Accepted: 03/26/2020] [Indexed: 12/15/2022] Open
Abstract
The increase in allergy prevalence observed in recent decades may be a consequence of early intestinal dysbiosis. The intestinal microbiota is formed in the first 1000 days of life, when it is particularly sensitive to various factors, such as the composition of the mother’s microbiota, type of delivery, infant’s diet, number of siblings, contact with animals, and antibiotic therapy. Breastfeeding and vaginal birth favorably affect the formation of an infant’s intestinal microbiota and protect against allergy development. The intestinal microbiota of these infants is characterized by an early dominance of Bifidobacterium, which may have a significant impact on the development of immune tolerance. Bifidobacterium breve is a species commonly isolated from the intestines of healthy breastfed infants and from human milk. This review outlines the most important environmental factors affecting microbiota formation and the importance of Bifidobacterium species (with a particular emphasis on Bifidobacterium breve) in microbiota modulation towards anti-allergic processes. In addition, we present the concept, which assumes that infant formulas containing specific probiotic Bifidobacterium breve strains and prebiotic oligosaccharides may be useful in allergy management in non-breastfed infants.
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Affiliation(s)
- Bożena Cukrowska
- Department of Pathology, The Children Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland;
- Correspondence: ; Tel.: +48-22-815-19-69
| | - Joanna B. Bierła
- Department of Pathology, The Children Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland;
| | - Magdalena Zakrzewska
- Department of Developmental Age Medicine and Paediatric Nursing, Faculty of Health Sciences, Medical University of Bialystok, Szpitalna St. 37, 15-295 Białystok, Poland; (M.Z.); (E.M.)
| | - Mark Klukowski
- Department of Pediatrics and Pulmonary Diseases, Faculty of Health Sciences, Medical University of Bialystok, Jerzego Waszyngtona St. 17, 15-274 Białystok, Poland;
| | - Elżbieta Maciorkowska
- Department of Developmental Age Medicine and Paediatric Nursing, Faculty of Health Sciences, Medical University of Bialystok, Szpitalna St. 37, 15-295 Białystok, Poland; (M.Z.); (E.M.)
- Department of Pediatrics and Pulmonary Diseases, Faculty of Health Sciences, Medical University of Bialystok, Jerzego Waszyngtona St. 17, 15-274 Białystok, Poland;
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19
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Paraimmunobiotic Bifidobacteria Modulate the Expression Patterns of Peptidoglycan Recognition Proteins in Porcine Intestinal Epitheliocytes and Antigen Presenting Cells. Cells 2019; 8:cells8080891. [PMID: 31416116 PMCID: PMC6721749 DOI: 10.3390/cells8080891] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 08/07/2019] [Accepted: 08/09/2019] [Indexed: 02/07/2023] Open
Abstract
Peptidoglycan recognition proteins (PGLYRPs) are a family of pattern recognition receptors (PRRs) that are able to induce innate immune responses through their binding to peptidoglycan (PGN), lipopolysaccharide, or lipoteichoic acid, or by interacting with other PRR-ligands. Recently, progress has been made in understanding the immunobiology of PGLYRPs in human and mice, however, their functions in livestock animals have been less explored. In this study, we characterized the expression patterns of PGLYRPs in porcine intestinal epithelial (PIE) cells and antigen-presenting cells (APCs) and their modulation by the interactions of host cells with PRR-ligands and non-viable immunomodulatory probiotics referred to as paraimmunobiotics. We demonstrated that PGLYRP-1, -2, -3, and -4 are expressed in PIE cells and APCs from Peyer’s patches, being PGLYPR-3 and -4 levels higher than PGLYRP-1 and -2. We also showed that PGLYRPs expression in APCs and PIE cells can be modulated by different PRR agonists. By using knockdown PIE cells for TLR2, TLR4, NOD1, and NOD2, or the four PGLYRPs, we demonstrated that PGLYRPs expressions would be required for activation and functioning of TLR2, TLR4, NOD1, and NOD2 in porcine epitheliocytes, but PGLYRPs activation would be independent of those PRR expressions. Importantly, we reported for the first time that PGLYRPs expression can be differentially modulated by paraimmunobiotic bifidobacteria in a strain-dependent manner. These results provide evidence for the use of paraimmunobiotic bifidobacteria as an alternative for the improvement of resistance to intestinal infections or as therapeutic tools for the reduction of the severity of inflammatory damage in diseases in which a role of PGLYRPs-microbe interaction has been demonstrated.
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Abstract
Intestinal dysbiosis is associated with a large number of disease processes including necrotizing enterocolitis and late-onset sepsis in preterm infants and colic and antibiotic-associated diarrhea in term infants. Probiotic microbes are increasingly administered to infants with the intent of decreasing risk of these acute diseases as well as chronic diseases of childhood such as asthma and atopic disease. The mechanisms by which probiotics decrease inflammation, decrease intestinal permeability, alter the intestinal microbiota, and influence metabolism have been discovered through both in vitro studies and in vivo in animal models. We review key mechanisms by which probiotic microbes improve health with emphasis on recent discoveries in the field.
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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: 28] [Impact Index Per Article: 4.7] [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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22
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Wang W, Sun M, Zheng YL, Sun LY, Qu SQ. Effects of Bifidobacterium infantis on cytokine-induced neutrophil chemoattractant and insulin-like growth factor-1 in the ileum of rats with endotoxin injury. World J Gastroenterol 2019; 25:2924-2934. [PMID: 31249450 PMCID: PMC6589735 DOI: 10.3748/wjg.v25.i23.2924] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 03/12/2019] [Accepted: 03/30/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The digestive tract is the maximal immunizing tissue in the body, and mucosal integrity and functional status of the gut is very important to maintain a healthy organism. Severe infection is one of the most common causes of gastrointestinal dysfunction, and the pathogenesis is closely related to endotoxemia and intestinal barrier injury. Bifidobacterium is one of the main probiotics in the human body that is involved in digestion, absorption, metabolism, nutrition, and immunity. Bifidobacterium plays an important role in maintaining the intestinal mucosal barrier integrity. This study investigated the protective mechanism of Bifidobacterium during ileal injury in rats.
AIM To investigate the effects of Bifidobacterium on cytokine-induced neutrophil chemoattractant (CINC) and insulin-like growth factor 1 (IGF-1) in the ileum of rats with endotoxin injury.
METHODS Preweaning rats were randomly divided into three groups: Control (group C), model (group E) and treatment (group T). Group E was intraperitoneally injected with lipopolysaccharide (LPS) to create an animal model of intestinal injury. Group T was intragastrically administered Bifidobacterium suspension 7 d before LPS. Group C was intraperitoneally injected with normal saline. The rats were killed at 2, 6 or 12 h after LPS or physiological saline injection to collect ileal tissue samples. The expression of ileal CINC mRNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR), and expression of ileal IGF-1 protein and mRNA was detected by immunohistochemistry and RT-PCR, respectively.
RESULTS The ileum of rats in Group C did not express CINC mRNA, ileums from Group E expressed high levels, which was then significantly decreased in Group T (F = 23.947, P < 0.05). There was no significant difference in CINC mRNA expression at different times (F = 0.665, P > 0.05). There was a high level of IGF-1 brown granules in ileal crypts and epithelial cells in Group C, sparse staining in Group E, and dark, dense brown staining in Group T. There was a significant difference between Groups C and E and Groups E and T (P < 0.05). There was no significant difference in IGF-1 protein expression at different times (F = 1.269, P > 0.05). IGF-1 mRNA expression was significantly different among the three groups (P < 0.05), though not at different times (F = 0.086, P > 0.05).
CONCLUSION Expression of CINC mRNA increased in the ileum of preweaning rats with endotoxin injury, and exogenous administration of Bifidobacterium reduced CINC mRNA expression. IGF-1 protein and mRNA expression decreased in the ileum of preweaning rats with endotoxin injury, and exogenous administration of Bifidobacterium prevented the decrease in IGF-1 expression. Bifidobacterium may increase IGF-1 expression and enhance intestinal immune barrier function in rats with endotoxin injury.
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Affiliation(s)
- Wei Wang
- Department of Pediatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Mei Sun
- Department of Pediatric Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Yu-Ling Zheng
- Department of Pediatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Liu-Yu Sun
- Department of Pediatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Shu-Qiang Qu
- Department of Pediatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
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Grases-Pintó B, Torres-Castro P, Abril-Gil M, Castell M, Rodríguez-Lagunas MJ, Pérez-Cano FJ, Franch À. A Preterm Rat Model for Immunonutritional Studies. Nutrients 2019; 11:nu11050999. [PMID: 31052461 PMCID: PMC6566403 DOI: 10.3390/nu11050999] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 04/26/2019] [Accepted: 04/29/2019] [Indexed: 12/14/2022] Open
Abstract
Neonates are born with an immature immune system, which develops during the first stages of life. This early immaturity is more acute in preterm newborns. The aim of the present study was to set up a preterm rat model, in which representative biomarkers of innate and adaptive immunity maturation that could be promoted by certain dietary interventions are established. Throughout the study, the body weight was registered. To evaluate the functionality of the intestinal epithelial barrier, in vivo permeability to dextrans was measured and a histomorphometric study was performed. Furthermore, the blood cell count, phagocytic activity of blood leukocytes and plasmatic immunoglobulins (Ig) were determined. Preterm rats showed lower erythrocyte and platelet concentration but a higher count of leukocytes than the term rats. Although there were no changes in the granulocytes’ ability to phagocytize, preterm monocytes had lower phagocytic activity. Moreover, lower plasma IgG and IgM concentrations were detected in preterm rats compared to full-term rats, without affecting IgA. Finally, the intestinal study revealed lower permeability in preterm rats and reduced goblet cell size. Here, we characterized a premature rat model, with differential immune system biomarkers, as a useful tool for immunonutritional studies aimed at boosting the development of the immune system.
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Affiliation(s)
- Blanca Grases-Pintó
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain.
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain.
| | - Paulina Torres-Castro
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain.
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain.
| | - Mar Abril-Gil
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain.
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain.
| | - Margarida Castell
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain.
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain.
| | - María J Rodríguez-Lagunas
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain.
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain.
| | - Francisco J Pérez-Cano
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain.
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain.
| | - Àngels Franch
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain.
- Nutrition and Food Safety Research Institute (INSA·UB), 08921 Santa Coloma de Gramenet, Spain.
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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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Jing Y, Peng F, Shan Y, Jiang J. Berberine reduces the occurrence of neonatal necrotizing enterocolitis by reducing the inflammatory response. Exp Ther Med 2018; 16:5280-5285. [PMID: 30542485 DOI: 10.3892/etm.2018.6871] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Accepted: 08/09/2018] [Indexed: 12/26/2022] Open
Abstract
Necrotizing enterocolitis (NEC) is a life-threatening disease that occurs in premature infants. The aim of the present study was to investigate the effects of berberine, an isoquinoline alkaloid mainly used to treat digestive diseases, in a rat model of NEC. NEC models were established in newborn rats via inhalation of N2 for 90 sec every 4 h and oral administration of 4 mg/kg/day lipopolysaccharides on days 0 and 1. Berberine was administered via oral gavage. In the NEC model group, Toll-like receptor (TLR)4, nuclear factor NF-κB (NF-κB), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were upregulated. Symptoms of NEC in the berberine intervention group were significantly relieved, with a clear reduction in the incidence of NEC compared with the NEC group. TLR4, NF-κB, iNOS, TNF-α, IL-6 and IL-10 expression was decreased following berberine intervention. Furthermore, the expression of mucin-2 (MUC2) and RNA polymerase σ factor SigA (SIgA) were decreased in the NEC model group and increased following berberine intervention, when compared with the untreated group. It was also demonstrated that the incidence of NEC was reduced following berberine administration, possibly owing to changes in the inflammatory responses. The results of the current study support a potential therapeutic role of berberine for the treatment of NEC.
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Affiliation(s)
- Yong Jing
- Department of Pediatric Surgery, The Second People's Hospital of Liaocheng, Linqing, Shandong 252600, P.R. China
| | - Fudong Peng
- Neonatal Intensive Care Unit, The Second People's Hospital of Liaocheng, Linqing, Shandong 252600, P.R. China
| | - Yufeng Shan
- Neonatal Intensive Care Unit, The Second People's Hospital of Liaocheng, Linqing, Shandong 252600, P.R. China
| | - Jingkai Jiang
- Department of Pediatric Surgery, The Second People's Hospital of Liaocheng, Linqing, Shandong 252600, P.R. China
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Athalye-Jape G, Rao S, Patole S. Effects of probiotics on experimental necrotizing enterocolitis: a systematic review and meta-analysis. Pediatr Res 2018; 83:16-22. [PMID: 28949953 DOI: 10.1038/pr.2017.218] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Accepted: 09/02/2017] [Indexed: 12/18/2022]
Abstract
BackgroundMeta-analyses of randomized controlled trials (RCTs) suggest that probiotics decrease the risk of necrotizing enterocolitis (NEC) in preterm infants. Many animal RCTs have evaluated probiotics for preventing NEC. We systematically reviewed the literature on this topic.MethodsThe protocol for systematic review of animal intervention studies (SYRCLE) was followed. Medline, Embase, ISI Web of Science, e-abstracts from the Pediatric Academic Society meetings, and other neonatal conferences were searched in December 2015 and August 2016. RCTs comparing probiotics vs. placebo/no probiotic were included.ResultsA total of 29 RCTs were included (Rats: 16, Mice: 7, Piglets: 3, Quail: 2, Rabbit: 1; N~2,310), with 21 reporting on histopathologically confirmed NEC; remaining 8 assessed only pathways of probiotic benefits. Twenty of the 21 RCTs showed that probiotics significantly reduced NEC. Pooling of data was possible for 16/21 RCTs. Meta-analysis using random-effects model showed that probiotics significantly decreased the risk of NEC (203/641 (31.7%) vs. 344/571 (60.2%); relative risk: 0.51; 95% confidence interval (CI): 0.42-0.62; P<0.00001; I2=44%; number needed to treat: 4; 95% CI: 2.9, 4.3).ConclusionProbiotics significantly reduced NEC via beneficial effects on immunity, inflammation, tissue injury, gut barrier, and intestinal dysbiosis.
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Affiliation(s)
- Gayatri Athalye-Jape
- Department of Neonatal Paediatrics, Princess Margaret Hospital for Children, Perth, Australia.,Department of Neonatal Paediatrics, KEM Hospital for Women, Perth, Australia.,Centre for Neonatal Research and Education, School of Paediatrics and Child Health, University of Western Australia, Perth, Australia
| | - Shripada Rao
- Department of Neonatal Paediatrics, Princess Margaret Hospital for Children, Perth, Australia.,Centre for Neonatal Research and Education, School of Paediatrics and Child Health, University of Western Australia, Perth, Australia
| | - Sanjay Patole
- Department of Neonatal Paediatrics, KEM Hospital for Women, Perth, Australia.,Centre for Neonatal Research and Education, School of Paediatrics and Child Health, University of Western Australia, Perth, Australia
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Athalye-Jape G, Rao S, Simmer K, Patole S. Bifidobacterium breve M-16V as a Probiotic for Preterm Infants: A Strain-Specific Systematic Review. JPEN J Parenter Enteral Nutr 2017; 42:677-688. [PMID: 28796951 DOI: 10.1177/0148607117722749] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 06/30/2017] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Bifidobacterium breve M-16V has been used as a probiotic in preterm infants. Probiotic strain-specific data are essential to guide clinical practice. OBJECTIVE To assess effects of B breve M-16V in preterm neonates. DESIGN A systematic review of randomized controlled trials (RCTs) and non-RCTs of B breve M-16V in preterm infants was conducted. Multiple databases, proceedings of Pediatric Academy Society, and other relevant conferences were searched in September 2016 and on January 5, 2017. RESULTS Five RCTs (n = 482) and 4 non-RCTs (n = 2496) were included. Of the 5 RCTs, 4 carried high/unclear risk of bias in many domains. Meta-analysis (fixed effects model) of RCTs showed no significant benefits on stage ≥2 necrotizing enterocolitis, late-onset sepsis, mortality, and postnatal age at full feeds. Meta-analysis of non-RCTs showed significant benefits on (1) late-onset sepsis-3 studies (n = 2452), odds ratio = 0.56 (95% CI, 0.45-0.71), P < .0001; (2) mortality-2 studies (n = 2319), odds ratio = 0.61 (95% CI, 0.44-0.84), P = .002; and (3) postnatal age at full feeds (days)-2 studies (n = 361), mean difference, -2.42 (95% CI, -2.55 to -2.3), P < .00001. There were no adverse effects from B breve M-16V. On Grading of Recommendations, Assessment, Development, and Evaluation analysis, the overall quality of evidence was deemed very low. CONCLUSIONS Current evidence is limited regarding the potential of B breve M-16V in preterm neonates. Adequately powered, preferably cluster RCTs are needed to confirm these findings.
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Affiliation(s)
- Gayatri Athalye-Jape
- Department of Neonatal Paediatrics, King Edward Memorial Hospital, Perth, Australia.,Department of Neonatal Paediatrics, Princess Margaret Hospital for Children, Perth, Australia.,Centre for Neonatal Research and Education, School of Paediatrics and Child Health, University of Western Australia, Perth, Australia
| | - Shripada Rao
- Department of Neonatal Paediatrics, King Edward Memorial Hospital, Perth, Australia.,Department of Neonatal Paediatrics, Princess Margaret Hospital for Children, Perth, Australia.,Centre for Neonatal Research and Education, School of Paediatrics and Child Health, University of Western Australia, Perth, Australia
| | - Karen Simmer
- Department of Neonatal Paediatrics, King Edward Memorial Hospital, Perth, Australia.,Centre for Neonatal Research and Education, School of Paediatrics and Child Health, University of Western Australia, Perth, Australia
| | - Sanjay Patole
- Department of Neonatal Paediatrics, King Edward Memorial Hospital, Perth, Australia.,Centre for Neonatal Research and Education, School of Paediatrics and Child Health, University of Western Australia, Perth, Australia
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Sugahara H, Yao R, Odamaki T, Xiao J. Differences between live and heat-killed bifidobacteria in the regulation of immune function and the intestinal environment. Benef Microbes 2017; 8:463-472. [DOI: 10.3920/bm2016.0158] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Probiotics are live microorganisms that confer a health benefit on the host, such as improvement of the intestinal environment, modulation of immune function and energy metabolism. Heat-killed probiotic strains have also been known to exhibit some physiological functions; however, the differences between live and heat-killed probiotics have not been well elucidated. In this study, we investigated the differences between live and heat-killed Bifidobacterium breve M-16V, a probiotic strain, in the regulation of immune function, intestinal metabolism and intestinal gene expression of the host using gnotobiotic mouse model and omics approaches. Both live and heat-killed cells of B. breve M-16V showed immune-modulating effects that suppressed pro-inflammatory cytokine production in spleen cells and affected intestinal metabolism; however, live cells exhibited a more remarkable effect in the regulation of intestinal metabolism and intestinal gene expression involved in nutrient metabolism. Our findings are valuable for considering the health benefits of live and heat-killed bacteria and the usefulness of different forms of probiotics.
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Affiliation(s)
- H. Sugahara
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., 1-83, 5-Chome, Higashihara, Zama-City, Kanagawa, Japan
| | - R. Yao
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., 1-83, 5-Chome, Higashihara, Zama-City, Kanagawa, Japan
| | - T. Odamaki
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., 1-83, 5-Chome, Higashihara, Zama-City, Kanagawa, Japan
| | - J.Z. Xiao
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., 1-83, 5-Chome, Higashihara, Zama-City, Kanagawa, Japan
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Abstract
A large number of randomized placebo-controlled clinical trials and cohort studies have demonstrated a decrease in the incidence of necrotizing enterocolitis with administration of probiotic microbes. These studies have prompted many neonatologists to adopt routine prophylactic administration of probiotics while others await more definitive studies and/or probiotic products with demonstrated purity and stable numbers of live organisms. Cross-contamination and inadequate sample size limit the value of further traditional placebo-controlled randomized controlled trials. Key areas for future research include mechanisms of protection, optimum probiotic species or strains (or combinations thereof) and duration of treatment, interactions between diet and the administered probiotic, and the influence of genetic polymorphisms in the mother and infant on probiotic response. Next generation probiotics selected based on bacterial genetics rather than ease of production and large cluster-randomized clinical trials hold great promise for NEC prevention.
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Affiliation(s)
- Mark A Underwood
- Division of Neonatology, UC Davis School of Medicine, Ticon 2, 2516 Stockton Blvd, Sacramento, CA 95817.
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30
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Vongbhavit K, Underwood MA. Prevention of Necrotizing Enterocolitis Through Manipulation of the Intestinal Microbiota of the Premature Infant. Clin Ther 2016; 38:716-32. [PMID: 26872618 DOI: 10.1016/j.clinthera.2016.01.006] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Accepted: 12/30/2015] [Indexed: 12/17/2022]
Abstract
PURPOSE In spite of four decades of research, necrotizing enterocolitis (NEC) remains the most common gastrointestinal complication in premature infants with high mortality and long-term morbidity. The composition of the intestinal microbiota of the premature infant differs dramatically from that of the healthy term infant and appears to be an important risk factor for NEC. METHODS We review the evidence of an association between intestinal dysbiosis and NEC and summarize published English language clinical trials and cohort studies involving attempts to manipulate the intestinal microbiota in premature infants. FINDINGS Promising NEC prevention strategies that alter the intestinal microbiota include probiotics, prebiotics, synbiotics, lacteroferrin, and human milk feeding. IMPLICATIONS Shaping the intestinal microbiota of the premature infant through human milk feeding and dietary supplements decreases the risk of NEC. Further studies to identify the ideal microbial composition and the most effective combination of supplements are indicated.
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Affiliation(s)
- Kannikar Vongbhavit
- Department of Pediatrics, HRH Princess Maha Chakri Sirindhorn Medical Center, Srinakharinwirot University, Nakornayok, Thailand; Department of Pediatrics, University of California Davis, Sacramento, California
| | - Mark A Underwood
- Department of Pediatrics, University of California Davis, Sacramento, California.
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Abstract
Premature infants are at increased risk for morbidity and mortality due to necrotizing enterocolitis (NEC) and sepsis. Probiotics decrease the risk of NEC and death in premature infants; however, mechanisms of action are unclear. A wide variety of probiotic species have been evaluated for potential beneficial properties in vitro, in animal models, and in clinical trials of premature infants. Although there is variation by species and even strain, common mechanisms of protection include attenuation of intestinal inflammation, apoptosis, dysmotility, permeability, supplanting other gut microbes through production of bacteriocins, and more effective use of available nutrients. Here, we review the most promising probiotics and what is known about their impact on the innate and adaptive immune response.
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Affiliation(s)
- Mark A Underwood
- Chief Division of Neonatology, School of Medicine, University of California at Davis, Sacramento, CA
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