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Gui L, Duan X, Wang H, Xie H, Zhang R, Jiang W, Tang W. Lactobacillus rhamnosus GG maintains gut microbiota stability and promotes intestinal adaptation via activated intestinal farnesoid X receptor signaling in short bowel syndrome. Commun Biol 2025; 8:816. [PMID: 40425822 DOI: 10.1038/s42003-025-08254-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 05/19/2025] [Indexed: 05/29/2025] Open
Abstract
Intestinal farnesoid X receptor (FXR) signaling plays a critical role in maintaining intestinal microbiota stability. In this study, we investigated the probiotic Lactobacillus rhamnosus GG (LGG) and its ability to promote intestinal adaptation and stabilize the gut microbiota by activating intestinal FXR signaling in short bowel syndrome (SBS). In patients with type I SBS, fecal microbial α-diversity was decreased, Proteobacteria abundance was increased, and Firmicutes, Actinobacteria, and Bacteroidetes abundance levels were decreased. In vitro, LGG supernatant (LGGs) upregulated FXR expression in Caco-2 cells and ileum organoids. In vivo, LGG supplementation significantly improved intestinal morphology in wild-type (WT) SBS mice, including increased villus height, crypt depth and goblet cell numbers. Serum fibroblast growth factor 15 (FGF15) levels increased and fecal Proteobacteria abundance decreased, while secondary bile acids rose and primary bile acids declined in WT SBS mice after LGG supplementation. In addition, LGG supplementation also increased occludin and FXR expression in WT SBS mice, but not in intestinal FXR knockout (FXRInt-KO) SBS animals. SBS disrupts FXR signaling and gut microbiota equilibrium. LGG counteracts these effects by activating intestinal FXR, which stabilizes microbiota composition, protects the mucosal barrier, and promotes intestinal adaptation both in vitro and in vivo.
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Affiliation(s)
- Linling Gui
- Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China
- Department of Neonatal Surgery, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science &Technology, Wuhan, China
| | - Xufei Duan
- Department of Neonatal Surgery, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science &Technology, Wuhan, China
| | - Hanfei Wang
- Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Hua Xie
- Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Ruyi Zhang
- Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Weiwei Jiang
- Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
| | - Weibing Tang
- Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
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Hou S, Yu J, Li Y, Zhao D, Zhang Z. Advances in Fecal Microbiota Transplantation for Gut Dysbiosis-Related Diseases. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2413197. [PMID: 40013938 PMCID: PMC11967859 DOI: 10.1002/advs.202413197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 01/22/2025] [Indexed: 02/28/2025]
Abstract
This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.
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Affiliation(s)
- Shuna Hou
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
- Department of general surgeryThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Jiachen Yu
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Yongshuang Li
- Department of general surgeryThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Duoyi Zhao
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Zhiyu Zhang
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
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Sutkus LT, Sommer KM, Li Z, Sutton BP, Donovan SD, Dilger RN. Experimentally induced colitis impacts myelin development and home-cage behavior in young pigs regardless of supplementation with oral gamma-cyclodextrin-encapsulated tributyrin. Front Neurosci 2025; 19:1484497. [PMID: 40231172 PMCID: PMC11994669 DOI: 10.3389/fnins.2025.1484497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 03/13/2025] [Indexed: 04/16/2025] Open
Abstract
Introduction Colitis, a chronic intestinal disorder that causes inflammation of the colonic mucosa, has been linked with structural brain abnormalities. To combat intestinal inflammation, researchers have investigated how nutritional supplementation, such as butyric acid, may ameliorate untoward effects. By encapsulating and using conjugates of butyrate, such as butyrate glycerides (i.e., tributyrin), slower release to the lower portions of the gastrointestinal tract can be achieved. Additionally, butyrate supplementation has been linked with supporting brain function and regulating integrity. Methods In the present study, a total of 24 intact male pigs were artificially reared and randomly assigned to 1 of 3 treatment conditions: (1) a control milk replacer (CON), (2) control plus oral dextran sodium sulfate (DSS) to induce colitis, or (3) control supplemented with 9.0 mM of gamma-cyclodextrin encapsulated tributyrin (TBCD) plus oral DSS (TBCD+DSS). Pigs were orally administered DSS treatments daily from postnatal day (PND) 14-18. Continuous video recording began on PND 3 and ceased on PND 27 or 28, with videos processed and analyzed for home-cage tracking behavior. On PND 26 or 27, pigs underwent neuroimaging procedures to assess overall brain anatomy (MPRAGE), microstructure (DTI), and myelin (MWF). Results and discussion Home-cage spatial preference was not altered prior to DSS dosing or during the overall study period. However, TBCD+DSS pigs spent less (p < 0.05) time within quadrant 4 when compared with CON pigs. Across almost all 29 brain regions assessed, absolute volumes were observed to be smaller in the TBCD+DSS group compared with CON and DSS groups. However, once individual volumes were assessed relative to the whole brain, most treatment effects dissipated other than for gray matter volume (p = 0.041). Diffusivity was found to be altered in several regions across treatment groups, thereby indicating differences in fiber organization. In areas like the hippocampus and thalamus, when fractional anisotropy (FA) values were highest for a given treatment, in the other diffusion metrics (mean, radial, axial diffusivity) values were lowest for that same treatment, indicating more organized cellular structure. Several other diffusion trends and differences were observed across various regions. Lastly, myelin water fraction (MWF) values were lowest in DSS-treated groups compared with CON (p < 0.05) for the whole brain and left/right cortices. Conclusion Overall, fiber organization and myelination were observed to be altered by experimentally induced colitis and contrary to expectations, tributyrin supplementation did not ameliorate these effects. Future work is warranted to investigate other protective nutritional mechanisms for colitis.
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Affiliation(s)
- Loretta T. Sutkus
- Neuroscience Program, University of Illinois, Urbana, IL, United States
| | - Kaitlyn M. Sommer
- Department of Animal Sciences, Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States
| | - Zimu Li
- Neuroscience Program, University of Illinois, Urbana, IL, United States
| | - Bradley P. Sutton
- Neuroscience Program, University of Illinois, Urbana, IL, United States
- Department of Bioengineering, University of Illinois, Urbana, IL, United States
- Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana, IL, United States
| | - Sharon D. Donovan
- Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL, United States
- Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States
| | - Ryan N. Dilger
- Neuroscience Program, University of Illinois, Urbana, IL, United States
- Department of Animal Sciences, Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States
- Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States
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Fu J, Zhao J, Shang H. Functions and mechanisms of nonstarch polysaccharides in monogastric animal production. Int J Biol Macromol 2024; 281:136488. [PMID: 39393723 DOI: 10.1016/j.ijbiomac.2024.136488] [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] [Received: 04/21/2024] [Revised: 09/06/2024] [Accepted: 10/08/2024] [Indexed: 10/13/2024]
Abstract
As natural active ingredients, polysaccharides are a class of biological macromolecules that are ubiquitous in living organisms and have antibacterial, antioxidant, antitumor and intestinal flora-regulating functions. Nonstarch polysaccharides (NSPs) are an important class of polysaccharides that include both soluble and insoluble nonstarch polysaccharides. As green feed additives, NSPs play important roles in promoting immunity and disease resistance in the body, regulating the intestinal microbial balance and improving the quality of animal products. NSPs regulate cell signal transduction mainly via interactions between short-chain fatty acids and G protein-coupled receptors and inhibiting the histone deacetylation pathway to protect the intestinal barrier in animals. In this paper, the composition, physiological functions, and molecular mechanisms of the gut protective effects of NSPs are reviewed to provide a reference for the application of NSPs in monogastric animal production.
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Affiliation(s)
- Jia Fu
- College of Forestry and Grassland Science, Jilin Agricultural University, Changchun 130118, China
| | - Jiangchao Zhao
- Department of Animal Science, University of Arkansas, Fayetteville 72701, USA
| | - Hongmei Shang
- College of Forestry and Grassland Science, Jilin Agricultural University, Changchun 130118, China; Jilin Provincial Key Laboratory of Tree and Grass Genetics and Breeding, Jilin Agricultural University, Changchun 130118, China.
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Liu H, Lu H, Wang Y, Yu C, He Z, Dong H. Unlocking the power of short-chain fatty acids in ameliorating intestinal mucosal immunity: a new porcine nutritional approach. Front Cell Infect Microbiol 2024; 14:1449030. [PMID: 39286812 PMCID: PMC11402818 DOI: 10.3389/fcimb.2024.1449030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 08/12/2024] [Indexed: 09/19/2024] Open
Abstract
Short-chain fatty acids (SCFAs), a subset of organic fatty acids with carbon chains ranging from one to six atoms in length, encompass acetate, propionate, and butyrate. These compounds are the endproducts of dietary fiber fermentation, primarily catalyzed by the glycolysis and pentose phosphate pathways within the gut microbiota. SCFAs act as pivotal energy substrates and signaling molecules in the realm of animal nutrition, exerting a profound influence on the intestinal, immune system, and intestinal barrier functions. Specifically, they contibute to 60-70% of the total energy requirements in ruminants and 10-25% in monogastric animals. SCFAs have demonstrated the capability to effectively modulate intestinal pH, optimize the absorption of mineral elements, and impede pathogen invasion. Moreover, they enhance the expression of proteins associated with intestinal tight junctions and stimulate mucus production, thereby refining intestinal tissue morphology and preserving the integrity of the intestinal structure. Notably, SCFAs also exert anti-inflammatory properties, mitigating inflammation within the intestinal epithelium and strengthening the intestinal barrier's defensive capabilities. The present review endeavors to synthesize recent findings regarding the role of SCFAs as crucial signaling intermediaries between the metabolic activities of gut microbiota and the status of porcine cells. It also provides a comprehensive overview of the current literature on SCFAs' impact on immune responses within the porcine intestinal mucosa.
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Affiliation(s)
- Haoyang Liu
- Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China
- Beijing Engineering Research Center of Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China
| | - Hongde Lu
- Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China
- Beijing Engineering Research Center of Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China
| | - Yuxuan Wang
- Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China
- Beijing Engineering Research Center of Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China
| | - Chenyun Yu
- Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China
- Beijing Engineering Research Center of Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China
| | - Zhiyuan He
- Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China
| | - Hong Dong
- Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China
- Beijing Engineering Research Center of Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China
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Piper HG, Bording-Jorgensen M, Veniamin S, Zhang Z, Suarez RG, Armstrong H, Silverman JA, Wine E. Intestinal microbial and metabolite profile in infants with small bowel stomas after bowel resection. J Pediatr Gastroenterol Nutr 2024; 79:705-715. [PMID: 39046027 DOI: 10.1002/jpn3.12327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 05/31/2024] [Accepted: 06/22/2024] [Indexed: 07/25/2024]
Abstract
BACKGROUND Infants with small bowel stomas (SBstoma) frequently struggle with absorption and rely on parenteral nutrition (PN). Intestinal absorption is difficult to predict based solely on intestinal anatomy. The purpose of this study was to characterize the microbiota and metabolic by-products within stoma effluent and correlate with clinical features and intestinal absorption. METHODS Prospective cohort study collecting stoma samples from neonates with SBstoma (N = 23) or colostomy control (N = 6) at initial enteral feed (first sample) and before stoma closure (last sample). Gut bacteriome (16S ribosomal RNA [rRNA] sequencing), short-chain fatty acids (SCFAs) and bile acids (BAs) were characterized along with volume and energy content of a 48 h collection via bomb calorimetry (last sample). Hierarchical clustering and linear regression were used to compare the bacteriome and BAs/SCFAs, to bowel length, PN, and growth. RESULTS Infants with ≤50% small bowel lost more fluid on average than those with >50% and controls (22, 18, 16 mL/kg/day, p = 0.013), but had similar energy losses (7, 10, 9 kcal/kg/day, p = 0.147). Infants growing poorly had enrichment of Proteobacteria compared to infants growing well (90% vs. 15%, p = 0.004). An increase in the ratio of secondary BAs within the small bowel over time, correlated with poor prognostic factors (≤50% small bowel, >50% of calories from PN, and poor growth). CONCLUSION Infants with SBstoma and poor growth have a unique bacteriome community and those with poor enteral tolerance have metabolic differences compared to infants with improved absorption.
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Affiliation(s)
- Hannah G Piper
- Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada
| | | | - Simona Veniamin
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Zhengxiao Zhang
- College of Food and Biological Engineering, Jimei University, Fujian, Xiamen, China
| | - Ricardo G Suarez
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Heather Armstrong
- Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Jason A Silverman
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Eytan Wine
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
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Correia AM, Genova JL, Kim SW, Abranches FF, Rocha GC. Autolyzed yeast and sodium butyrate supplemented alone to diets promoted improvements in performance, intestinal health and nutrient transporter in weaned piglets. Sci Rep 2024; 14:11885. [PMID: 38789563 PMCID: PMC11126410 DOI: 10.1038/s41598-024-62551-9] [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] [Received: 03/16/2024] [Accepted: 05/17/2024] [Indexed: 05/26/2024] Open
Abstract
This study investigated the effects of supplemental nucleotides, autolyzed yeast (Saccharomyces cerevisiae), and sodium butyrate in diets for nursery pigs on growth performance, diarrhea incidence, blood profile, intestinal morphology, mRNA expression of nutrient transporters, inflammatory markers, antioxidant profile, and tight junction proteins in the small intestine. One hundred eighty 21-day-old pigs (5.17 ± 0.57 kg) were assigned in a randomized block design to 1 of 4 dietary treatments: (1) CON: control, basal diet, (2) NUC: CON + nucleotides, (3) YSC: CON + lysed yeast S. cerevisiae, (4) ASB: CON + acidifier sodium butyrate. Pigs were fed for 24 days, phase 1 (21-32 days) and 2 (32-45 days). During phase 1, YSC and ASB improved average daily gain (ADG) and feed conversion (FC) compared with CON. At the overall period, ASB improved ADG and YSC improved FC compared with CON. The NUC diet did not affect growth performance. The ASB increased ileal villus height compared to CON. The YSC and ASB reduced the number of Peyer's patches in the ileum compared with CON. The YSC increased mRNA expression of nutrient transporters (SMCT2, MCT1, and PepT1), tight junction proteins (OCL and ZO-1), antioxidants (GPX), and IL1-β in the jejunum compared with CON. The ASB increased mRNA expression of nutrient transporters (SGLT1 and MCT1), tight junction proteins (OCL and ZO-1), and antioxidants (GPX and SOD) compared with CON. In conclusion, autolyzed yeast and sodium butyrate promoted growth performance by improving the integrity of the intestinal barrier, the mRNA expression of nutrient transporters, and antioxidant enzymes in the jejunum of nursery pigs whereas supplementation of nucleotides did not show such effects.
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Affiliation(s)
- Amanda Medeiros Correia
- Muscle Biology and Nutrigenomics Laboratory, Department of Animal Science, Universidade Federal de Viçosa, Minas Gerais, Brazil
| | - Jansller Luiz Genova
- Muscle Biology and Nutrigenomics Laboratory, Department of Animal Science, Universidade Federal de Viçosa, Minas Gerais, Brazil
| | - Sung Woo Kim
- Department of Animal Science, North Carolina State University, Raleigh, NC, 27695, USA
| | - Fernanda Fialho Abranches
- Muscle Biology and Nutrigenomics Laboratory, Department of Animal Science, Universidade Federal de Viçosa, Minas Gerais, Brazil
| | - Gabriel Cipriano Rocha
- Muscle Biology and Nutrigenomics Laboratory, Department of Animal Science, Universidade Federal de Viçosa, Minas Gerais, Brazil.
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Jiang L, Xu J, Cheng SY, Wang Y, Cai W. The gut microbiome and intestinal failure-associated liver disease. Hepatobiliary Pancreat Dis Int 2023; 22:452-457. [PMID: 37453856 DOI: 10.1016/j.hbpd.2023.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 07/05/2023] [Indexed: 07/18/2023]
Abstract
Intestinal failure-associated liver disease (IFALD) is a common hepatobiliary complication resulting from long-term parenteral nutrition (PN) in patients with intestinal failure. The spectrum of IFALD ranges from cholestasis, steatosis, portal fibrosis, to cirrhosis. Development of IFALD is a multifactorial process, in which gut dysbiosis plays a critical role in its initiation and progression in conjunction with increased intestinal permeability, activation of hepatic immune responses, and administration of lipid emulsion. Gut microbiota manipulation including pre/probiotics, fecal microbiota transplantation, and antibiotics has been studied in IFALD with varying success. In this review, we summarize current knowledge on the taxonomic and functional changes of gut microbiota in preclinical and clinical studies of IFALD. We also review the function of microbial metabolites and associated signalings in the context of IFALD. By providing microbiota-targeted interventions aiming to optimize PN-induced liver injury, our review provides perspectives for future basic and translational investigations in the field.
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Affiliation(s)
- Lu Jiang
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Shanghai Institute for Pediatric Research, Shanghai 200092, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
| | - Juan Xu
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
| | - Si-Yang Cheng
- Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
| | - Ying Wang
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
| | - Wei Cai
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Shanghai Institute for Pediatric Research, Shanghai 200092, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China; Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
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Phelps HM, Warner BW. Intestinal adaptation and rehabilitation. Semin Pediatr Surg 2023; 32:151314. [PMID: 37276784 DOI: 10.1016/j.sempedsurg.2023.151314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Massive intestinal resection is a regrettably necessary but life-saving intervention for progressive or fulminant necrotizing enterocolitis (NEC). However, the resultant short bowel syndrome (SBS) poses its own array of challenges and complications. Within hours of such an abrupt loss of intestinal length, the intestine begins to adapt. Our ability to understand this process of intestinal adaptation has proven critical in our ability to clinically treat the challenging problem of short bowel syndrome. This review first highlights key data relating to intestinal adaptation including structural and functional changes, biochemical regulation, and other factors affecting the magnitude of intestinal adaptation responses. We then focus on intestinal rehabilitation as it relates to strategies to enhance intestinal adaptation while meeting nutritional needs and preventing complications of parenteral nutrition.
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Affiliation(s)
- Hannah M Phelps
- Division of Pediatric Surgery, Department of Surgery, Washington University in St. Louis School of Medicine, 9901 Wohl Hospital, Campus Box 8109, St. Louis, MO 63110, USA.
| | - Brad W Warner
- Division of Pediatric Surgery, Department of Surgery, Washington University in St. Louis School of Medicine, 9901 Wohl Hospital, Campus Box 8109, St. Louis, MO 63110, USA
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Caporilli C, Giannì G, Grassi F, Esposito S. An Overview of Short-Bowel Syndrome in Pediatric Patients: Focus on Clinical Management and Prevention of Complications. Nutrients 2023; 15:nu15102341. [PMID: 37242224 DOI: 10.3390/nu15102341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 04/26/2023] [Accepted: 05/15/2023] [Indexed: 05/28/2023] Open
Abstract
Short-bowel syndrome (SBS) in pediatric age is defined as a malabsorptive state, resulting from congenital malformations, significant small intestine surgical resection or disease-associated loss of absorption. SBS is the leading cause of intestinal failure in children and the underlying cause in 50% of patients on home parental nutrition. It is a life-altering and life-threatening disease due to the inability of the residual intestinal function to maintain nutritional homeostasis of protein, fluid, electrolyte or micronutrient without parenteral or enteral supplementation. The use of parenteral nutrition (PN) has improved medical care in SBS, decreasing mortality and improving the overall prognosis. However, the long-term use of PN is associated with the incidence of many complications, including liver disease and catheter-associated malfunction and bloodstream infections (CRBSIs). This manuscript is a narrative review of the current available evidence on the management of SBS in the pediatric population, focusing on prognostic factors and outcome. The literature review showed that in recent years, the standardization of management has demonstrated to improve the quality of life in these complex patients. Moreover, the development of knowledge in clinical practice has led to a reduction in mortality and morbidity. Diagnostic and therapeutic decisions should be made by a multidisciplinary team that includes neonatologists, pediatric surgeons, gastroenterologists, pediatricians, nutritionists and nurses. A significant improvement in prognosis can occur through the careful monitoring of nutritional status, avoiding dependence on PN and favoring an early introduction of enteral nutrition, and through the prevention, diagnosis and aggressive treatment of CRSBIs and SIBO. Multicenter initiatives, such as research consortium or data registries, are mandatory in order to personalize the management of these patients, improve their quality of life and reduce the cost of care.
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Affiliation(s)
- Chiara Caporilli
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Giuliana Giannì
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Federica Grassi
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Susanna Esposito
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
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Michiels J, Truffin D, Majdeddin M, Van Poucke M, Van Liefferinge E, Van Noten N, Vandaele M, Van Kerschaver C, Degroote J, Peelman L, Linder P. Gluconic acid improves performance of newly weaned piglets associated with alterations in gut microbiome and fermentation. Porcine Health Manag 2023; 9:10. [PMID: 37016456 PMCID: PMC10074721 DOI: 10.1186/s40813-023-00305-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 01/23/2023] [Indexed: 04/06/2023] Open
Abstract
BACKGROUND Weaning is a critical phase in the pigs' life and gut health might be compromised. Gluconic acid was shown to be poorly absorbed but readily fermented to butyrate in the gut which in turn can improve gut function. Hence, a total of 144 weaning pigs were fed the experimental diets for 42 days. Three treatments were replicated in 8 pens with 6 piglets each: control; low dietary dose of gluconic acid, 9 g/kg; and high dietary dose of gluconic acid, 18 g/kg. After 21 days, one piglet from each pen was sampled for blood haematology and biochemistry, fore- and hindgut digesta characteristics and microbiota, and distal small intestinal histo-morphological indices and gene expression. RESULTS Feeding gluconic acid enhanced performance in period d 0-14 post-weaning, in particular feed intake was increased (P = 0.028), though the high dose did not show benefits over the low dose. Regarding d 0-42, feed intake was elevated (P = 0.026). At d 21, piglets fed 18 g/kg gluconic acid showed a trend for lower number of total white blood cells (P = 0.060), caused by particularly lower numbers of lymphocytes as compared to control (P = 0.028). Highly reduced plasma urea was found for groups fed gluconic acid, it amounted to 2.6 and 2.6 mmol/L for the 9 and 18 g/kg level, respectively, as compared to 3.8 mmol/L in control (P = 0.003). Feeding gluconic acid promoted the relative abundance of lactic-acid-producing and acid-utilizing bacteria. In distal small intestine, Lactobacillus amylovorus increased substantially from 11.3 to 82.6% for control and gluconic acid 18 g/kg, respectively (P < 0.05). In mid-colon, the butyrate producers Faecalibacterium prausnitzii (P > 0.05) and Megasphaera elsdenii (P < 0.05) showed highest abundance in gluconic acid 18 g/kg. Consequently, in caecum and mid-colon, increased relative molar percentage of butyrate were found, e.g., 10.0, 12.9 et 14.7% in caecum for gluconic acid at 0, 9, and 18 g/kg, respectively (P = 0.046). Elevated mRNA anti-inflammatory cytokine and survival signalling levels in distal small intestinal mucosa were found by feeding gluconic acid which might be mediated by butyrate. CONCLUSIONS Gluconic acid may have potential to alleviate the postweaning growth-check in pigs by altering microbiota composition and fermentation in the gut.
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Affiliation(s)
- Joris Michiels
- Laboratory for Animal Nutrition and Animal Product Quality, Department of Animal Sciences and Aquatic Ecology, Ghent University, Campus Coupure, Coupure Links 653, 9000, Ghent, Belgium.
| | - Damien Truffin
- Roquette Frères, 1 rue de La Haute Loge, 62136, Lestrem, France
| | - Maryam Majdeddin
- Laboratory for Animal Nutrition and Animal Product Quality, Department of Animal Sciences and Aquatic Ecology, Ghent University, Campus Coupure, Coupure Links 653, 9000, Ghent, Belgium
| | - Mario Van Poucke
- Department of Veterinary and Biosciences, Ghent University, Heidestraat 19, 9820, Merelbeke, Belgium
| | - Elout Van Liefferinge
- Laboratory for Animal Nutrition and Animal Product Quality, Department of Animal Sciences and Aquatic Ecology, Ghent University, Campus Coupure, Coupure Links 653, 9000, Ghent, Belgium
| | - Noémie Van Noten
- Laboratory for Animal Nutrition and Animal Product Quality, Department of Animal Sciences and Aquatic Ecology, Ghent University, Campus Coupure, Coupure Links 653, 9000, Ghent, Belgium
| | - Mario Vandaele
- Laboratory for Animal Nutrition and Animal Product Quality, Department of Animal Sciences and Aquatic Ecology, Ghent University, Campus Coupure, Coupure Links 653, 9000, Ghent, Belgium
| | - Céline Van Kerschaver
- Laboratory for Animal Nutrition and Animal Product Quality, Department of Animal Sciences and Aquatic Ecology, Ghent University, Campus Coupure, Coupure Links 653, 9000, Ghent, Belgium
| | - Jeroen Degroote
- Laboratory for Animal Nutrition and Animal Product Quality, Department of Animal Sciences and Aquatic Ecology, Ghent University, Campus Coupure, Coupure Links 653, 9000, Ghent, Belgium
| | - Luc Peelman
- Department of Veterinary and Biosciences, Ghent University, Heidestraat 19, 9820, Merelbeke, Belgium
| | - Pierre Linder
- Roquette Frères, 1 rue de La Haute Loge, 62136, Lestrem, France
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Mohamed Elfadil O, Mundi MS, Abdelmagid MG, Patel A, Patel N, Martindale R. Butyrate: More Than a Short Chain Fatty Acid. Curr Nutr Rep 2023:10.1007/s13668-023-00461-4. [PMID: 36763294 DOI: 10.1007/s13668-023-00461-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/13/2023] [Indexed: 02/11/2023]
Abstract
PURPOSE OF REVIEW The mechanistic understanding of the importance and the potential benefits of the gut microbiome has exploded in potential roles in human health and disease. Short chain fatty acids (SCFAs), including butyrate, are one of the key metabolic end products that has been a major focus of microbiome understanding. This brief review aims to describe butyrate's relation to certain biological concepts and their clinical application. RECENT FINDINGS Butyrate has reportedly been described as a potent pro-resolution molecule that has a significant role in maintaining gut immunity, supporting gut barrier function, regulation of histone deacetylase (HDAC), and numerous systemic roles. Further research is needed to explore potential benefits of adding SCFAs for patients receiving total parenteral nutrition. Butyrate plays several biological roles in intestinal epithelium anti-inflammatory pathways with clear benefits in numerous acute and chronic disease states and overall human health helping to maintain homeostasis.
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Affiliation(s)
- Osman Mohamed Elfadil
- Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, USA.
| | - Manpreet S Mundi
- Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, USA
| | - Marwa G Abdelmagid
- Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, USA
| | - Ankitaben Patel
- Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, USA
| | - Nishant Patel
- Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, USA
| | - Robert Martindale
- Division of Gastrointestinal and General Surgery, School of Medicine, Oregon Health and Sciences University, Portland, OR, USA
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13
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MAFLD and Celiac Disease in Children. Int J Mol Sci 2023; 24:ijms24021764. [PMID: 36675276 PMCID: PMC9866925 DOI: 10.3390/ijms24021764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/13/2023] [Accepted: 01/14/2023] [Indexed: 01/18/2023] Open
Abstract
Celiac disease (CD) is an immune-mediated systemic disorder elicited by the ingestion of gluten whose clinical presentation ranges from the asymptomatic form to clinical patterns characterized by multiple systemic involvement. Although CD is a disease more frequently diagnosed in patients with symptoms of malabsorption such as diarrhea, steatorrhea, weight loss, or failure to thrive, the raised rate of overweight and obesity among general pediatric and adult populations has increased the possibility to diagnose celiac disease in obese patients as well. Consequently, it is not difficult to also find obesity-related disorders in patients with CD, including "metabolic associated fatty liver disease" (MAFLD). The exact mechanisms linking these two conditions are not yet known. The going assumption is that a gluten-free diet (GFD) plays a pivotal role in determining an altered metabolic profile because of the elevated content of sugars, proteins, saturated fats, and complex carbohydrates, and the higher glycemic index of gluten-free products than gluten-contained foods, predisposing individuals to the development of insulin resistance. However, recent evidence supports the hypothesis that alterations in one of the components of the so-called "gut-liver axis" might contribute to the increased afflux of toxic substances to the liver triggering the liver fat accumulation and to the subsequent hepatocellular damage. The aim of this paper was to describe the actual knowledge about the factors implicated in the pathogenesis of hepatic steatosis in pediatric patients with CD. The presented review allows us to conclude that the serological evaluations for CD with anti-transglutaminase antibodies, should be a part of the general workup in the asymptomatic patients with "non-alcoholic fatty liver disease" (NAFLD) when metabolic risk factors are not evident, and in the patients with steatohepatitis when other causes of liver disease are excluded.
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14
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Fourati S, Dumay A, Roy M, Willemetz A, Ribeiro-Parenti L, Mauras A, Mayeur C, Thomas M, Kapel N, Joly F, Le Gall M, Bado A, Le Beyec J. Fecal microbiota transplantation in a rodent model of short bowel syndrome: A therapeutic approach? Front Cell Infect Microbiol 2023; 13:1023441. [PMID: 36936775 PMCID: PMC10020656 DOI: 10.3389/fcimb.2023.1023441] [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] [Received: 08/19/2022] [Accepted: 02/03/2023] [Indexed: 03/06/2023] Open
Abstract
Extensive intestinal resection leads to Short Bowel Syndrome (SBS), the main cause of chronic intestinal failure. Colon preservation is crucial for spontaneous adaptation, to improve absorption and reduce parenteral nutrition dependence. Fecal microbiota transplantation (FMT), a promising approach in pathologies with dysbiosis as the one observed in SBS patients, was assessed in SBS rats with jejuno-colonic anastomosis. The evolution of weight and food intake, the lenght of intestinal villi and crypts and the composition of fecal microbiota of Sham and SBS rats, transplanted or not with high fat diet rat microbiota, were analyzed. All SBS rats lost weight, increased their food intake and exhibited jejunal and colonic hyperplasia. Microbiota composition of SBS rats, transplanted or not, was largely enriched with Lactobacillaceae, and α- and β-diversity were significantly different from Sham. The FMT altered microbiota composition and α- and β-diversity in Sham but not SBS rats. FMT from high fat diet rats was successfully engrafted in Sham, but failed to take hold in SBS rats, probably because of the specific luminal environment in colon of SBS subjects favoring aero-tolerant over anaerobic bacteria. Finally, the level of food intake in SBS rats was positively correlated with their Lactobacillaceae abundance. Microbiota transfer must be optimized and adapted to this specific SBS environment.
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Affiliation(s)
- Salma Fourati
- UMR-S1149, Centre de recherche sur l’inflammation, INSERM, Universite Paris Cite, Paris, France
- Sorbonne Université, AP-HP, Hôpital de la Pitié‐Salpêtrière‐Charles Foix, Service de Biochimie Endocrinienne et Oncologique, Paris, France
- Paris Center for Microbiome Medicine, Federation Hospitalo-Universitaire, Paris, France
| | - Anne Dumay
- UMR-S1149, Centre de recherche sur l’inflammation, INSERM, Universite Paris Cite, Paris, France
| | - Maryline Roy
- UMR-S1149, Centre de recherche sur l’inflammation, INSERM, Universite Paris Cite, Paris, France
| | - Alexandra Willemetz
- UMR-S1149, Centre de recherche sur l’inflammation, INSERM, Universite Paris Cite, Paris, France
| | - Lara Ribeiro-Parenti
- UMR-S1149, Centre de recherche sur l’inflammation, INSERM, Universite Paris Cite, Paris, France
- AP-HP, Hôpital Bichat -Claude Bernard, Service de chirurgie Générale OEsogastrique et Bariatrique, Paris, France
| | - Aurélie Mauras
- Paris Center for Microbiome Medicine, Federation Hospitalo-Universitaire, Paris, France
- UMR1319 - Micalis Institute, Institut National de Recherche pour l’Agriculture, l’alimentation et l’environnement (INRAE), AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France
| | - Camille Mayeur
- Paris Center for Microbiome Medicine, Federation Hospitalo-Universitaire, Paris, France
- UMR1319 - Micalis Institute, Institut National de Recherche pour l’Agriculture, l’alimentation et l’environnement (INRAE), AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France
| | - Muriel Thomas
- Paris Center for Microbiome Medicine, Federation Hospitalo-Universitaire, Paris, France
- UMR1319 - Micalis Institute, Institut National de Recherche pour l’Agriculture, l’alimentation et l’environnement (INRAE), AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France
| | - Nathalie Kapel
- Paris Center for Microbiome Medicine, Federation Hospitalo-Universitaire, Paris, France
- UMR-S 1139, INSERM, Universite Paris Cite, Paris, France
- AP-HP, Hôpital de la Pitié‐Salpêtrière‐Charles Foix, Service de Coprologie fonctionnelle, Paris, France
| | - Francisca Joly
- UMR-S1149, Centre de recherche sur l’inflammation, INSERM, Universite Paris Cite, Paris, France
- Department of gastroenterology, IBD and nutrition Support, AP‐HP, CRMR MarDi, Hôpital Beaujon, Clichy, France
| | - Maude Le Gall
- UMR-S1149, Centre de recherche sur l’inflammation, INSERM, Universite Paris Cite, Paris, France
| | - André Bado
- UMR-S1149, Centre de recherche sur l’inflammation, INSERM, Universite Paris Cite, Paris, France
| | - Johanne Le Beyec
- UMR-S1149, Centre de recherche sur l’inflammation, INSERM, Universite Paris Cite, Paris, France
- Sorbonne Université, AP-HP, Hôpital de la Pitié‐Salpêtrière‐Charles Foix, Service de Biochimie Endocrinienne et Oncologique, Paris, France
- Paris Center for Microbiome Medicine, Federation Hospitalo-Universitaire, Paris, France
- *Correspondence: Johanne Le Beyec, ;;
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15
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Nutritional Management of Intestinal Failure due to Short Bowel Syndrome in Children. Nutrients 2022; 15:nu15010062. [PMID: 36615720 PMCID: PMC9823779 DOI: 10.3390/nu15010062] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/19/2022] [Accepted: 12/20/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The most common cause of intestinal failure (IF) in childhood remains short bowel syndrome (SBS), where bowel mass is significantly reduced due to a congenital atresia or resection and parenteral nutrition (PN) needed. Home PN has improved outcome and quality of life, but the long-term therapeutic goal is to achieve enteral autonomy whilst avoiding long term complications. This paper is aimed at discussing nutritional strategies available to clinicians caring for these patients. METHODS A literature search was performed from 1992 to 2022 using Pubmed, MEDLINE and Cochrane Database of Systematic Reviews, and recent guidelines were reviewed. In the absence of evidence, recommendations reflect the authors' expert opinion. RESULTS Consensus on the best possible way of feeding children with IF-SBS is lacking and practice varies widely between centres. Feeding should commence as soon as possible following surgery. Oral feeding is the preferred route and breast milk (BM) the first milk of choice in infants. Donor BM, standard preterm or term formula are alternatives in the absence of maternal BM. Extensively hydrolysed or amino acid-based feeds are used when these are not tolerated. Solids should be introduced as soon as clinically appropriate. Children are encouraged to eat by mouth and experience different tastes and textures to avoid oral aversion. Aggressive weaning of PN and tube (over-) feeding are now discouraged. CONCLUSIONS To date, uniform agreement on the optimal type of feed, timing of food introduction and feeding regime used is lacking and great difference in practice remains. There is need for more research to establish common treatment protocols.
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Cerdó T, García-Santos JA, Rodríguez-Pöhnlein A, García-Ricobaraza M, Nieto-Ruíz A, G. Bermúdez M, Campoy C. Impact of Total Parenteral Nutrition on Gut Microbiota in Pediatric Population Suffering Intestinal Disorders. Nutrients 2022; 14:4691. [PMID: 36364953 PMCID: PMC9658482 DOI: 10.3390/nu14214691] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 11/01/2022] [Accepted: 11/04/2022] [Indexed: 08/10/2023] Open
Abstract
Parenteral nutrition (PN) is a life-saving therapy providing nutritional support in patients with digestive tract complications, particularly in preterm neonates due to their gut immaturity during the first postnatal weeks. Despite this, PN can also result in several gastrointestinal complications that are the cause or consequence of gut mucosal atrophy and gut microbiota dysbiosis, which may further aggravate gastrointestinal disorders. Consequently, the use of PN presents many unique challenges, notably in terms of the potential role of the gut microbiota on the functional and clinical outcomes associated with the long-term use of PN. In this review, we synthesize the current evidence on the effects of PN on gut microbiome in infants and children suffering from diverse gastrointestinal diseases, including necrotizing enterocolitis (NEC), short bowel syndrome (SBS) and subsequent intestinal failure, liver disease and inflammatory bowel disease (IBD). Moreover, we discuss the potential use of pre-, pro- and/or synbiotics as promising therapeutic strategies to reduce the risk of severe gastrointestinal disorders and mortality. The findings discussed here highlight the need for more well-designed studies, and harmonize the methods and its interpretation, which are critical to better understand the role of the gut microbiota in PN-related diseases and the development of efficient and personalized approaches based on pro- and/or prebiotics.
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Affiliation(s)
- Tomás Cerdó
- Maimonides Institute for Research in Biomedicine of Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, Spain
| | - José Antonio García-Santos
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - Anna Rodríguez-Pöhnlein
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - María García-Ricobaraza
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - Ana Nieto-Ruíz
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - Mercedes G. Bermúdez
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - Cristina Campoy
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
- Spanish Network of Biomedical Research in Epidemiology and Public Health (CIBERESP), Granada’s Node, Carlos III Health Institute, Avda. Monforte de Lemos 5, 28028 Madrid, Spain
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17
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Sommer KM, Jespersen JC, Sutkus LT, Lee Y, Donovan SM, Dilger RN. Oral gamma-cyclodextrin-encapsulated tributyrin supplementation in young pigs with experimentally induced colitis. J Anim Sci 2022; 100:skac314. [PMID: 36161319 PMCID: PMC9671115 DOI: 10.1093/jas/skac314] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 09/23/2022] [Indexed: 11/13/2022] Open
Abstract
Disruption of intestinal integrity and barrier function due to tissue inflammation has negative implications on overall growth and well-being in young pigs. In this study, we investigated the effects of oral gamma-cyclodextrin-encapsulated tributyrin (TBCD) in young pigs experiencing dextran sodium sulfate (DSS)-induced colitis. Pigs (n = 32 boars) were weaned from the sow at postnatal day (PND) 2, allotted to treatment based on the litter of origin and body weight (BW), and reared artificially over a 26-d feeding period. Treatment groups included: 1) nutritionally adequate (control) milk replacer, no DSS (Control n = 8), 2) control milk replacer plus oral DSS (DSS, n = 7), and 3) control diet supplemented with 8.3 g of TBCD per kg of reconstituted milk replacer plus oral DSS (TBCD + DSS, n = 8). Colitis was induced by administering DSS at 1.25 g of DSS/kg BW daily in a reconstituted milk replacer from PND 14-18. Milk replacer and water were provided ad libitum throughout the 26-d study. All the data were analyzed using a one-way ANOVA using the MIXED procedure of SAS. Control and DSS pigs had similar BW throughout the study, while TBCD + DSS pigs exhibited decreased (P < 0.05) BW starting at approximately PND 15. Additionally, average daily gain (ADG) before and after initiation of DSS dosing, along with over the total study duration, was decreased (P < 0.05) in pigs receiving TBCD + DSS compared with the Control. Milk disappearance was decreased (P < 0.05) in TBCD + DSS pigs when compared with Control and DSS groups. Both the concentration and molar ratio of cecal butyrate concentrations were increased (P < 0.05) in TBCD + DSS pigs compared with the Control group. The DSS and TBCD + DSS treatments also increased (P < 0.05) butyrate concentrations in the luminal contents with the proximal colon compared with Control. TBCD + DSS and DSS pigs had increased (P < 0.05) mucosal width in the distal colon compared with Control, thereby indicating heightened intestinal inflammation. Overall, oral supplementation of encapsulated tributyrin increased the concentration of butyrate in the colon, but was unable to mitigate the negative effects of DSS-induced colitis.
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Affiliation(s)
- Kaitlyn M Sommer
- Department of Animal Sciences, University of Illinois, Urbana, IL, USA
| | | | - Loretta T Sutkus
- Department of Animal Sciences, University of Illinois, Urbana, IL, USA
| | - Youngsoo Lee
- Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL, USA
| | - Sharon M Donovan
- Department of Animal Sciences, University of Illinois, Urbana, IL, USA
| | - Ryan N Dilger
- Department of Animal Sciences, University of Illinois, Urbana, IL, USA
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Słupecka-Ziemilska M, Pierzynowski SG, Szczurek P, Pierzynowska K, Wychowański P, Seklecka B, Koperski M, Starzyńska A, Szkopek D, Donaldson J, Andrzejewski K, Woliński J. Milk Formula Enriched with Sodium Butyrate Influences Small Intestine Contractility in Neonatal Pigs. Nutrients 2022; 14:nu14204301. [PMID: 36296985 PMCID: PMC9608939 DOI: 10.3390/nu14204301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 10/07/2022] [Accepted: 10/10/2022] [Indexed: 11/07/2022] Open
Abstract
Butyrate, a by-product of gut bacteria fermentation as well as the digestion of fat in mother’s milk, exerts a wide spectrum of beneficial effects in the gastrointestinal tissues. The present study aimed to determine the effects of sodium butyrate on small intestine contractility in neonatal piglets. Piglets were fed milk formula alone (group C) or milk formula supplemented with sodium butyrate (group B). After a 7-day treatment period, isometric recordings of whole-thickness segments of the duodenum and middle jejunum were obtained by electric field stimulation under the influence of increasing doses of Ach (acetylocholine) in the presence of TTX (tetrodotoxin) and atropine. Moreover, structural properties of the intestinal wall were assessed, together with the expression of cholinergic and muscarinic receptors (M1 and M2). In both intestinal segments (duodenum and middle jejunum), EFS (electric field stimulation) impulses resulted in increased contractility and amplitude of contractions in group B compared to group C. Additionally, exposure to dietary butyrate led to a significant increase in tunica muscularis thickness in the duodenum, while mitotic and apoptotic indices were increased in the middle jejunum. The expression of M1 and M2 receptors in the middle jejunum was significantly higher after butyrate treatment. The results indicate increased cholinergic signaling and small intestinal growth and renewal in response to feeding with milk formula enriched with sodium butyrate in neonatal piglets.
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Affiliation(s)
- Monika Słupecka-Ziemilska
- Department of Human Epigenetics, Mossakowski Medical Research Institute Polish Academy of Sciences, 02-106 Warszawa, Poland
| | - Stefan Grzegorz Pierzynowski
- Department of Medical Biology, Institute of Rural Health, 20-090 Lublin, Poland
- SGP + Group, 231 32 Trelleborg, Sweden
- Department of Biology, Lund University, Sölvegatan 35, 223 62 Lund, Sweden
| | - Paulina Szczurek
- Department of Animal Nutrition and Feed Sciences, National Research Institute of Animal Production, 32-083 Balice, Poland
| | - Kateryna Pierzynowska
- Department of Biology, Lund University, Sölvegatan 35, 223 62 Lund, Sweden
- Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, 05-110 Jabłonna, Poland
- Correspondence: (K.P.); (J.W.)
| | - Piotr Wychowański
- Division of Oral Surgery and Implantology, Department of Head and Neck, Institute of Clinical Dentistry, Oral Surgery and Implantology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS-Universita Cattolica del Sacro Coure, 00168 Rome, Italy
| | | | - Maciej Koperski
- Department of Human Epigenetics, Mossakowski Medical Research Institute Polish Academy of Sciences, 02-106 Warszawa, Poland
| | - Anna Starzyńska
- Departament of Oral Surgery, Medical University of Gdańsk, 7 Dębinki Street, 80-211 Gdańsk, Poland
| | - Dominika Szkopek
- Large Animal Models Laboratory, The Kielanowski Institute of Animal Physiology and Nutrition, 05-110 Jabłonna, Poland
| | - Janine Donaldson
- SGP + Group, 231 32 Trelleborg, Sweden
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa
| | - Krzysztof Andrzejewski
- Department of Orthopedics and Traumatology, Veteran’s Memorial Hospital, Medical University of Łódź, 90-549 Łódź, Poland
| | - Jarosław Woliński
- Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, 05-110 Jabłonna, Poland
- Large Animal Models Laboratory, The Kielanowski Institute of Animal Physiology and Nutrition, 05-110 Jabłonna, Poland
- Correspondence: (K.P.); (J.W.)
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19
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Pauline M, Fouhse J, Hinchliffe T, Wizzard P, Patrick Nation, Huynh H, Wales P, Willing B, Turner J. Probiotic Treatment Versus Empiric Oral Antibiotics for Managing Dysbiosis in Short Bowel Syndrome: Impact on the Mucosal and Stool Microbiota, Short Chain Fatty Acids and Adaptation. JPEN J Parenter Enteral Nutr 2022; 46:1828-1838. [PMID: 35383975 DOI: 10.1002/jpen.2377] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 03/22/2022] [Accepted: 03/25/2022] [Indexed: 11/07/2022]
Abstract
BACKGROUND Infants and children with short bowel syndrome (SBS) are presumed to be at risk of gut microbial dysbiosis with potential sequelae of bacterial overgrowth that include sepsis, D-lactic acidosis, mucosal inflammation and malabsorption. In neonatal piglets with SBS, we compared intestinal microbial composition, short chain fatty acids (SCFA) and adaptation given probiotic treatment (Lactobacillus and Bifidobacterium spp.) versus oral metronidazole. METHODS Following 75% distal small intestinal resection, piglets were allocated to: probiotic (PRO, 500mg BID n=7), metronidazole (MET, 15mg/kg BID n=8) and placebo (PLA, 500mg BID n=8). After 10 days of parenteral and enteral nutrition, 16S rRNA gene amplicon sequencing (colon tissue and stool) were undertaken and SCFA analysis (stool and colon effluent) performed using gas chromatography. RESULTS In colon, Shannon diversity was higher for PRO compared to MET and PLA (p=0.002). PRO and PLA increased abundance of Bacteroidetes species (e.g. Bacteroides fragilis), compared to MET (p<0.001). PRO compared to PLA increased abundance of Firmicutes species (e.g. Lactobacillus fermentum) (p<0.001). MET increased abundance of Proteobacteria members, predominately Enterobacteriaceae compared to PRO (p=0.004). In stool, microbial findings were similar and SCFA (butyrate) concentrations were highest for PRO (p=0.003) compared to MET. CONCLUSION In pediatric SBS, the empiric use of oral antibiotics, such as metronidazole, is common for presumed clinical consequences of microbial dysbiosis. In this study of SBS piglets, that approach was associated with decreased microbial diversity and increased abundance of potentially inflammatory Proteobacteria. In contrast, a probiotic treatment using Lactobacillus and Bifidobacterium spp. increased both diversity and SCFAs. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Mirielle Pauline
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Janelle Fouhse
- Faculty of Agriculture, Life and Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - Tierah Hinchliffe
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Pamela Wizzard
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Patrick Nation
- Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada
| | - Hien Huynh
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Paul Wales
- Department of Surgery, Cincinnati Children's Hospital Medical Center and University of Cincinnati
| | - Benjamin Willing
- Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada
| | - Justine Turner
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
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Jiang L, Wang Y, Xiao Y, Wang Y, Yan J, Schnabl B, Cai W. Role of the Gut Microbiota in Parenteral Nutrition-Associated Liver Disease: From Current Knowledge to Future Opportunities. J Nutr 2022; 152:377-385. [PMID: 34734271 DOI: 10.1093/jn/nxab380] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 09/02/2021] [Accepted: 10/26/2021] [Indexed: 11/13/2022] Open
Abstract
Parenteral nutrition-associated liver disease (PNALD) refers to a spectrum of conditions that can develop cholestasis, steatosis, fibrosis, and cirrhosis in the setting of parenteral nutrition (PN) use. Patient risk factors include short bowel syndrome, bacterial overgrowth and translocation, disturbance of hepatobiliary circulation, and lack of enteral feeding. A growing body of evidence suggests an intricate linkage between the gut microbiota and the pathogenesis of PNALD. In this review, we highlight current knowledge on the taxonomic and functional changes in the gut microbiota that might serve as noninvasive biomarkers. We also discuss the function of microbial metabolites and associated signaling pathways in the pathogenesis of PNALD. By providing the perspectives of microbiota-host interactions in PNALD for basic and translational research and summarizing current limitations of microbiota-based approaches, this review paves the path for developing novel and precise microbiota-based therapies in PNALD.
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Affiliation(s)
- Lu Jiang
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Shanghai Institute for Pediatric Research, Shanghai, China.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Ying Wang
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Yongtao Xiao
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Shanghai Institute for Pediatric Research, Shanghai, China.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Yong Wang
- Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Junkai Yan
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Shanghai Institute for Pediatric Research, Shanghai, China.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Bernd Schnabl
- Department of Medicine, University of California San Diego, La Jolla, CA, USA.,Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA
| | - Wei Cai
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Shanghai Institute for Pediatric Research, Shanghai, China.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.,Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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21
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Joo SS, Gu BH, Park YJ, Rim CY, Kim MJ, Kim SH, Cho JH, Kim HB, Kim M. Porcine Intestinal Apical-Out Organoid Model for Gut Function Study. Animals (Basel) 2022; 12:ani12030372. [PMID: 35158695 PMCID: PMC8833427 DOI: 10.3390/ani12030372] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 01/24/2022] [Accepted: 01/31/2022] [Indexed: 11/24/2022] Open
Abstract
Simple Summary Pigs have been used in various animal model studies on the gastrointestinal tract (GIT) across both animal science and biomedical science fields. Recently, intestinal organoids have been used as a research tool for the GIT, and they have also been applied to farm animals, including pigs. However, to our knowledge, no functional studies of the porcine intestine using intestinal organoids have been conducted to date. In the present study, we developed two porcine intestinal organoid models (basal-out and apical-out organoids) and compared their characteristics. We also confirmed the possibility of conducting research related to intestinal functions, such as nutrient uptake and gut barrier function. The present study suggests that porcine intestinal organoids can be used as potential models for future GIT mechanism studies, such as host–microbe interactions, harmful ingredient tests, and nutritional research. Abstract Pig models provide valuable research information on farm animals, veterinary, and biomedical sciences. Experimental pig gut models are used in studies on physiology, nutrition, and diseases. Intestinal organoids are powerful tools for investigating intestinal functions such as nutrient uptake and gut barrier function. However, organoids have a basal-out structure and need to grow in the extracellular matrix, which causes difficulties in research on the intestinal apical membrane. We established porcine intestinal organoids from jejunum tissues and developed basal-out and apical-out organoids using different sub-culture methods. Staining and quantitative real-time PCR showed the difference in axis change of the membrane and gene expression of epithelial cell marker genes. To consider the possibility of using apical-out organoids for intestinal function, studies involving fatty acid uptake and disruption of the epithelial barrier were undertaken. Fluorescence fatty acid was more readily absorbed in apical-out organoids than in basal-out organoids within the same time. To determine whether apical-out organoids form a functional barrier, a fluorescent dextran diffusion assay was performed. Hence, we successfully developed porcine intestinal organoid culture systems and showed that the porcine apical-out organoid model is ideal for the investigation of the intestinal environment. It can be used in future studies related to the intestine across various research fields.
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Affiliation(s)
- Sang-Seok Joo
- Department of Animal Science, College of Natural Resources & Live Science, Pusan National University, Miryang 50463, Korea; (S.-S.J.); (Y.-J.P.); (C.-Y.R.)
| | - Bon-Hee Gu
- Life and Industry Convergence Research Institute, Pusan National University, Mirayng 50463, Korea;
| | - Yei-Ju Park
- Department of Animal Science, College of Natural Resources & Live Science, Pusan National University, Miryang 50463, Korea; (S.-S.J.); (Y.-J.P.); (C.-Y.R.)
| | - Chae-Yun Rim
- Department of Animal Science, College of Natural Resources & Live Science, Pusan National University, Miryang 50463, Korea; (S.-S.J.); (Y.-J.P.); (C.-Y.R.)
| | - Min-Ji Kim
- Animal Nutrition and Physiology Division, National Institute of Animal Science, Rural Development Administration, Wanju 55365, Korea; (M.-J.K.); (S.-H.K.)
| | - Sang-Ho Kim
- Animal Nutrition and Physiology Division, National Institute of Animal Science, Rural Development Administration, Wanju 55365, Korea; (M.-J.K.); (S.-H.K.)
| | - Jin-Ho Cho
- Department of Animal Science, Chungbuk National University, Cheongju 28644, Korea;
| | - Hyeun-Bum Kim
- Department of Animal Resources and Science, Dankook University, Cheonan 31116, Korea;
| | - Myunghoo Kim
- Department of Animal Science, College of Natural Resources & Live Science, Pusan National University, Miryang 50463, Korea; (S.-S.J.); (Y.-J.P.); (C.-Y.R.)
- Life and Industry Convergence Research Institute, Pusan National University, Mirayng 50463, Korea;
- Correspondence: ; Tel.: +82-55-350-5516; Fax: +82-55-350-5519
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22
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Papadopoulos GA, Poutahidis T, Chalvatzi S, Kroustallas F, Karavanis E, Fortomaris P. Effects of a tributyrin and monolaurin blend compared to high ZnO levels on growth performance, faecal microbial counts, intestinal histomorphometry and immunohistochemistry in weaned piglets: A field study in two pig herds. Res Vet Sci 2022; 144:54-65. [DOI: 10.1016/j.rvsc.2022.01.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 09/08/2021] [Accepted: 01/12/2022] [Indexed: 01/20/2023]
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23
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Toni T, Alverdy J, Gershuni V. Re-examining chemically defined liquid diets through the lens of the microbiome. Nat Rev Gastroenterol Hepatol 2021; 18:903-911. [PMID: 34594028 PMCID: PMC8815794 DOI: 10.1038/s41575-021-00519-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/31/2021] [Indexed: 12/13/2022]
Abstract
Trends in nutritional science are rapidly shifting as information regarding the value of eating unprocessed foods and its salutary effect on the human microbiome emerge. Unravelling the evolution and ecology by which humans have harboured a microbiome that participates in every facet of health and disease is daunting. Most strikingly, the host habitat has sought out naturally occurring foodstuff that can fulfil its own metabolic needs and also the needs of its microbiota, each of which remain inexorably connected to one another. With the introduction of modern medicine and complexities of critical care, came the assumption that the best way to feed a critically ill patient is by delivering fibre-free chemically defined sterile liquid foods (that is, total enteral nutrition). In this Perspective, we uncover the potential flaws in this assumption and discuss how emerging technology in microbiome sciences might inform the best method of feeding malnourished and critically ill patients.
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Affiliation(s)
- Tiffany Toni
- University of Chicago, Pritzker School of Medicine, Chicago, IL, USA
| | - John Alverdy
- University of Chicago, Pritzker School of Medicine, Chicago, IL, USA
| | - Victoria Gershuni
- University of Pennsylvania, Department of Surgery, Philadelphia, PA, USA and Washington University in St Louis, Department of Surgery, St Louis, MO, USA,Corresponding author
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24
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Xu E, Chen C, Fu J, Zhu L, Shu J, Jin M, Wang Y, Zong X. Dietary fatty acids in gut health: Absorption, metabolism and function. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2021; 7:1337-1344. [PMID: 34786506 PMCID: PMC8570925 DOI: 10.1016/j.aninu.2021.09.010] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 09/17/2021] [Accepted: 09/26/2021] [Indexed: 12/23/2022]
Abstract
In biological responses, fatty acids (FA) are absorbed and metabolized in the form of substrates for energy production. The molecular structures (number of double bonds and chain length) and composition of dietary FA impact digestion, absorption and metabolism, and the biological roles of FA. Recently, increasing evidence indicates that FA are essentially utilized as an energy source and are signaling molecules that exert physiological activity of gut microbiota and immune responses. In addition, FA could serve as natural ligands for orphan G protein-coupled receptors (GPCR), also called free fatty acid receptors (FFAR), which intertwine metabolic and immune systems via multiple mechanisms. The present review explores the recent findings on FA absorption and its impact on gut health, particularly addressing the mechanism by which dietary FA potentially influences intestinal microbiota and epithelial functions. Also, this work attempts to uncover research ideas for devising future strategies for manipulating the composition of dietary FA to regulate gut health and support a normal immune system for metabolic and immune disorders.
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Affiliation(s)
- E. Xu
- Key Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, College of Aniaml Science, Guizhou University, 550025 Guiyang, China
| | - Chao Chen
- Key Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, College of Aniaml Science, Guizhou University, 550025 Guiyang, China
| | - Jie Fu
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, 310058 Hangzhou, China
| | - Luoyi Zhu
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, 310058 Hangzhou, China
| | - Junlan Shu
- Key Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, College of Aniaml Science, Guizhou University, 550025 Guiyang, China
| | - Mingliang Jin
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, 310058 Hangzhou, China
- Key Laboratory of Animal Nutrition and Feed Science in Eastern China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, 310058 Hangzhou, China
| | - Yizhen Wang
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, 310058 Hangzhou, China
- Key Laboratory of Animal Nutrition and Feed Science in Eastern China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, 310058 Hangzhou, China
| | - Xin Zong
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, 310058 Hangzhou, China
- Key Laboratory of Animal Nutrition and Feed Science in Eastern China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, 310058 Hangzhou, China
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25
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Fan L, Lee JH. Enteral feeding and the microbiome in critically ill children: a narrative review. Transl Pediatr 2021; 10:2778-2791. [PMID: 34765500 PMCID: PMC8578772 DOI: 10.21037/tp-20-349] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Accepted: 04/09/2021] [Indexed: 01/10/2023] Open
Abstract
OBJECTIVE This narrative review summarizes our current knowledge on the interplay between enteral nutrition (EN) and gut microbiota in critically ill children, using examples from two commonly encountered diagnoses in the pediatric intensive care unit (PICU): severe sepsis and acute respiratory distress syndrome (ARDS). This review will also highlight potential areas of therapeutic interventions that should be explored in future studies. BACKGROUND Critically ill children display extreme dysbiosis in their gut microbiome. Factors within the PICU that are often associated with dysbiosis include the use of broad-spectrum antibiotics, proton-pump inhibitors (PPIs), intravenous morphine, and fasting. Dysbiosis can potentially lead to adverse clinical outcomes (e.g., nosocomial infection, and prolonged hospitalization). EN may modulate dysbiosis. The gut microbiota is involved in the breaking down of macronutrients, mainly carbohydrates and proteins. Fermentation of undigestible carbohydrate (e.g., inulin and oligosaccharides), and amino acids by large intestine microbiota produces short chain fatty acids (SCFAs). SCFAs serve as the main fuel source for enterocytes and help to maintain healthy gut lining. Changes to selected components of macronutrients can result in alterations in gut microbiome and have potentially beneficial effects in patients in the PICU. METHODS A comprehensive search of the MEDLINE, Cochrane Library and Google Scholar databases was conducted using appropriate MESH terms and keywords. In this narrative review, we provide a summary of current knowledge on effect of EN on gut microbiota in pediatric studies, but also describes animal- and lab-based, as well as adult studies where relevant. CONCLUSIONS The gut microbiome can be altered by dietary modifications and common PICU practices and treatment. Although there are strong associations in restoring eubiosis and improvement in clinical outcomes, proving causality remains challenging. Further microbiome research is needed to provide mechanistic insights into the impact of the ever changing gut microbiome. In the future, new microbiota targeted therapies could potentially be the treatment of challenging PICU conditions and restore homeostasis in these children.
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Affiliation(s)
- Lijia Fan
- Division of Paediatric Critical Care, Department of Paediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, Singapore, Singapore
| | - Jan Hau Lee
- Children's Intensive Care Unit, KK Women's and Children's Hospital, Singapore, Singapore.,Duke-NUS Medical School, Singapore, Singapore
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26
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Maito CD, Melo ADB, Oliveira ACDFD, Genova JL, Filho JRE, Macedo REFD, Monteiro KM, Weber SH, Koppenol A, Costa LB. Simultaneous feeding of calcium butyrate and tannin extract decreased the incidence of diarrhea and proinflammatory markers in weaned piglets. Anim Biosci 2021; 35:87-95. [PMID: 34237915 PMCID: PMC8738937 DOI: 10.5713/ab.21.0011] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Accepted: 05/28/2021] [Indexed: 01/19/2023] Open
Abstract
OBJECTIVE This study was conducted to investigate the effect of associating calcium butyrate with tannin extract, compared to an antimicrobial on the growth performance, incidence of diarrhea, intestinal histology, immune-expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor α (TNF-α) in piglets. METHODS Seventy-two piglets (36 barrows and 36 gilts) weaned at 28±2 d and initial body weight of 7.17±1.07 kg were allocated to 3 treatments in a randomized complete block design with 8 replicates per treatment and 3 animals per experimental unit. Treatments were composed of NC, negative control: basal diet without additives; PC, positive control: basal diet + 40 mg/kg of colistin sulfate; or BT, basal diet + calcium butyrate + tannin extract. The butyrate and tannin inclusion levels were 0.15% in the pre-starter phase and 0.075% in the starter phase. Incidence of diarrhea was monitored daily, and on d 14 and 35 of experiment, 1 animal from each experimental unit was slaughtered to collect intestinal samples. RESULTS No significant differences were observed for growth performance. The butyrate-and tannin-based additive resulted in reduced (p<0.05) incidence of diarrhea in piglets during d 1 to 14 and d 1 to 35 in comparison with the other treatments. Piglets that consumed the diet containing the calcium-butyrate and tannin showed a lower (p<0.05) crypt depth in the duodenum than those receiving the NC treatment at 14 d of experimentation. The BT treatment provided a lower (p<0.05) immune-expression of COX-2 at 14 d and TNF-α at 35 d in the duodenum. CONCLUSION Association between calcium butyrate and tannin extract resulted in a significant decrease in the incidence of diarrhea and inflammatory process in the duodenum of piglets. Therefore, calcium-butyrate combined with tannin could be a part of an alternative program to reduce the use of antimicrobials in the diet of weaned piglets.
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Affiliation(s)
- Camila Demarco Maito
- Graduate Program of Animal Science, School of Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná 80215- 901, Brazil
| | - Antonio Diego Brandão Melo
- Graduate Program of Animal Science, School of Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná 80215- 901, Brazil
| | | | - Jansller Luiz Genova
- Graduate Program of Animal Science, School of Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná 80215- 901, Brazil
| | - Jair Rodini Engracia Filho
- Graduate Program of Animal Science, School of Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná 80215- 901, Brazil
| | - Renata Ernlund Freitas de Macedo
- Graduate Program of Animal Science, School of Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná 80215- 901, Brazil
| | - Kelly Mazutti Monteiro
- Graduate Program of Animal Science, School of Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná 80215- 901, Brazil
| | - Saulo Henrique Weber
- Graduate Program of Animal Science, School of Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná 80215- 901, Brazil
| | | | - Leandro Batista Costa
- Graduate Program of Animal Science, School of Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná 80215- 901, Brazil
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27
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The Interplay between Nutrition, Innate Immunity, and the Commensal Microbiota in Adaptive Intestinal Morphogenesis. Nutrients 2021; 13:nu13072198. [PMID: 34206809 PMCID: PMC8308283 DOI: 10.3390/nu13072198] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 06/20/2021] [Accepted: 06/23/2021] [Indexed: 12/15/2022] Open
Abstract
The gastrointestinal tract is a functionally and anatomically segmented organ that is colonized by microbial communities from birth. While the genetics of mouse gut development is increasingly understood, how nutritional factors and the commensal gut microbiota act in concert to shape tissue organization and morphology of this rapidly renewing organ remains enigmatic. Here, we provide an overview of embryonic mouse gut development, with a focus on the intestinal vasculature and the enteric nervous system. We review how nutrition and the gut microbiota affect the adaptation of cellular and morphologic properties of the intestine, and how these processes are interconnected with innate immunity. Furthermore, we discuss how nutritional and microbial factors impact the renewal and differentiation of the epithelial lineage, influence the adaptation of capillary networks organized in villus structures, and shape the enteric nervous system and the intestinal smooth muscle layers. Intriguingly, the anatomy of the gut shows remarkable flexibility to nutritional and microbial challenges in the adult organism.
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28
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Zhou H, Sun J, Ge L, Liu Z, Chen H, Yu B, Chen D. Exogenous infusion of short-chain fatty acids can improve intestinal functions independently of the gut microbiota. J Anim Sci 2021; 98:5988194. [PMID: 33205812 DOI: 10.1093/jas/skaa371] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Accepted: 11/16/2020] [Indexed: 12/14/2022] Open
Abstract
The present experiment was conducted to investigate the effects of exogenously infused short-chain fatty acids (SCFAs) on the growth development and intestinal functions in a germ-free (GF) pig model. Twelve hysterectomy-derived newborn piglets were reared in six sterile isolators. All piglets were hand-fed Co60-γ-irradiated sterile milk powder for 21 d and then were switched to sterile feed for another 21 d. During the second 21-d period, GF piglets (n = 6) were orally infused with 25 mL/kg sterile saline per day, and SCFA piglets (n = 6) were orally infused with 25 mL/kg SCFAs mixture (acetic, propionic, and butyric acids, 45, 15, and 11 mM, respectively) per day. We observed the concentrations of SCFAs in serum and intestine, and the messenger ribonucleic acid (mRNA) abundance of G-protein-coupled receptor-43 in the ileum was increased (P < 0.05) in the SCFA group. Meanwhile, oral infusion of SCFAs enhanced (P < 0.05) the contents of glucagon-like peptide-2 in the jejunum and serum and tended to increase the villi height in the ileum (P < 0.10). Besides, the activities of lipase, trypsin, sucrase, lactase, Na+-K+-adenosine triphosphatase ([ATPase] P < 0.05), and Ca2+-Mg2+-ATPase (P < 0.10) were stimulated and the mRNA expressions of solute carrier family 7 (SLC7A1) and regeneration protein (REG)-ΙΙΙ γ in the jejunum (P < 0.05) were upregulated in the SCFA group. Additionally, SCFAs infusion downregulated the mRNA abundances of interleukin (IL)-1β and IL-6 in the jejunum, ileum, or colon (P < 0.05) and increased the counts of white blood cell, neutrophils, and lymphocyte in the blood (P < 0.05). Collectively, exogenous infusion of SCFAs might improve intestinal health through promoting intestinal development and absorption function, and enhancing intestinal immune function, and these effects were occur independently of the gut microbiota.
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Affiliation(s)
- Hua Zhou
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China
| | - Jing Sun
- Chongqing Academy of Animal Sciences, Rongchang, Chongqing, China
| | - Liangpeng Ge
- Chongqing Academy of Animal Sciences, Rongchang, Chongqing, China
| | - Zuohua Liu
- Chongqing Academy of Animal Sciences, Rongchang, Chongqing, China
| | - Hong Chen
- College of Food Science, Sichuan Agricultural University, Ya'an, Sichuan, China
| | - Bing Yu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China
| | - Daiwen Chen
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China
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29
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Microbiota reprogramming for treatment of alcohol-related liver disease. Transl Res 2020; 226:26-38. [PMID: 32687975 PMCID: PMC7572584 DOI: 10.1016/j.trsl.2020.07.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 07/01/2020] [Accepted: 07/13/2020] [Indexed: 02/08/2023]
Abstract
In the past decade knowledge has expanded regarding the importance of the gut microbiota in maintaining intestinal homeostasis and overall health. During this same time, we have also gained appreciation for the role of the gut-liver axis in the development of liver diseases. Alcohol overconsumption is one of the leading causes of liver failure globally. However, not all people with alcohol use disorder progress to advanced stages of liver disease. With advances in technology to investigate the gut microbiome and metabolome, we are now beginning to delineate alcohol's effects on the gut microbiome in relation to liver disease. This review presents our current understanding on the role of the gut microbiota during alcohol exposure, and various therapeutic attempts that have been made to reprogram the gut microbiota with the goal of alleviating alcoholic-related liver disease.
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30
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Shi X, Monaco MH, Donovan SM, Lee Y. Encapsulation of tributyrin by gamma-cyclodextrin: Complexation, spray drying, and in vitro fermentation. J Food Sci 2020; 85:2986-2993. [PMID: 32935856 DOI: 10.1111/1750-3841.15440] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Revised: 06/30/2020] [Accepted: 08/10/2020] [Indexed: 11/29/2022]
Abstract
Butyrate is a short-chain fatty acid (SCFA) known for support in gastrointestinal (GI) health. Tributyrin (TB) could be used as an alternate source of butyrate. The objectives of this study were to encapsulate TB using gamma-cyclodextrin (CD) by spray-drying and to investigate the physicochemical and the fermentation properties of TB/CD complex. The TB/CD complex precipitated in water with an average stoichiometry of 1:1.3 of TB:CD. At a 1:2 molar ratio of TB:CD, TB was fully retained in the spray-dried TB/CD complex. The spray-dried TB/CD complex showed crystalline structure, supported by both X-ray diffraction spectra and scanning electron microscopy images. The TB/CD complex at 1:2 molar ratio was fermented and several SCFAs, including butyrate, were produced in an in vitro test using piglets' ileal and colonic contents. A dose-dependent increase in the butyrate concentration in both ileum and ascending colon was observed. Approximately, 426 and 1189 μmole butyrate was produced per gram of TB/CD powder at 9 mM treatment in ileum and ascending colon, respectively. Thus, the production of the TB/CD complex using spray drying is feasible and the complex has the potential for food applications to improve intestinal health. PRACTICAL APPLICATION: The findings in this study can be applied to produce encapsulated tributyrin with gamma-cyclodextrin efficiently using spray-drying. The TB/CD complex was highly fermentable and caused an increase in the butyrate concentration in both ileum and ascending colon, which can be incorporated in foods to enhance butyrate delivery to the GI tract to assist gut health.
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Affiliation(s)
- Xueqian Shi
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Champaign, IL, USA
| | - Marcia H Monaco
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Champaign, IL, USA
| | - Sharon M Donovan
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Champaign, IL, USA
| | - Youngsoo Lee
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Champaign, IL, USA
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Yu M, Li Z, Chen W, Wang G, Rong T, Liu Z, Wang F, Ma X. Hermetia illucens larvae as a Fishmeal replacement alters intestinal specific bacterial populations and immune homeostasis in weanling piglets. J Anim Sci 2020; 98:5810268. [PMID: 32191809 DOI: 10.1093/jas/skz395] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Accepted: 02/12/2020] [Indexed: 12/11/2022] Open
Abstract
Hermetia illucens larvae meal (HILM) are rich in proteins and chitin, and represent an innovative feed ingredient for animals. However, little is known about the intestinal bacteria and immune homeostasis response of HILM as a fishmeal replacement on weanling piglets. Thus, this study aimed to investigate the changes in specific ileal and cecal bacterial populations and their metabolic profiles, and ileal immune indexes in weanling piglets fed with a diet containing HILM. A total of 128 weanling piglets were fed either a basal diet or 1 of 3 diets with 1%, 2%, and 4% HILM (HI0, HI1, HI2, and HI4, respectively). Each group consisted of 8 pens (replicates), with 4 pigs per pen. After 28 d of feeding, 8 barrows per treatment were euthanized, the ileal and cecal digesta, and ileal mucosa were collected for analyzing bacterial population and metabolic profiles, and immune indexes, respectively. Results showed that HILM increased (P < 0.05, maximum in HI2) the number of Lactobacillus and Bifidobacterium in the ileum and cecum, but quadratically decreased (P < 0.05, minimum in HI2) the number of Escherichia coli. In the cecum, the number of Firmicutes, Ruminococcus, Clostridium cluster IV, and Prevotella showed a quadratic response to increasing (P < 0.05, maximum in HI2) HILM levels. Lactate and butyrate concentrations in the ileum and cecum were quadratically increased (P < 0.05, maximum in HI2) with increasing HILM levels. In the cecum, the amines, phenol, and indole compounds concentrations were quadratically decreased (P < 0.05, minimum in HI2) with increasing HILM levels, while total short-chain fatty acids and acetate concentrations were quadratically increased (P < 0.05, maximum in HI2). In the ileum, the TLR4, NF-κB, MyD88, and TNF-α mRNA expressions were quadratically decreased (P < 0.05, minimum in HI2) with increasing HILM levels, while the mRNA expression of IL-10, barrier function (MUC1, ZO-1, Occludin, and Claudin-2), and development-related genes (IGF-1, GLP-2, and EGF) was quadratically increased (P < 0.05, maximum in HI2). Furthermore, the changes in the mucosal gene expression were associated with changes in the bacterial populations and their metabolites. Collectively, these results showed that a diet supplemented with 2% HILM affected specific bacterial populations and metabolic profiles, and maintained ileal immune status. These findings provide new insights into the use of insect meal as a suitable alternative protein source for swine feeding.
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Affiliation(s)
- Miao Yu
- Institute of Animal Science, Guangdong Academy of Agricultural Sciences, State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture, Guangdong Key Laboratory of Animal Breeding and Nutrition, Guangdong Engineering Technology Research Center of Animal Meat quality and Safety Control and Evaluation, Guangzhou, Guangdong, China
| | - Zhenming Li
- Institute of Animal Science, Guangdong Academy of Agricultural Sciences, State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture, Guangdong Key Laboratory of Animal Breeding and Nutrition, Guangdong Engineering Technology Research Center of Animal Meat quality and Safety Control and Evaluation, Guangzhou, Guangdong, China
| | - Weidong Chen
- Institute of Animal Science, Guangdong Academy of Agricultural Sciences, State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture, Guangdong Key Laboratory of Animal Breeding and Nutrition, Guangdong Engineering Technology Research Center of Animal Meat quality and Safety Control and Evaluation, Guangzhou, Guangdong, China
| | - Gang Wang
- Institute of Animal Science, Guangdong Academy of Agricultural Sciences, State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture, Guangdong Key Laboratory of Animal Breeding and Nutrition, Guangdong Engineering Technology Research Center of Animal Meat quality and Safety Control and Evaluation, Guangzhou, Guangdong, China
| | - Ting Rong
- Institute of Animal Science, Guangdong Academy of Agricultural Sciences, State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture, Guangdong Key Laboratory of Animal Breeding and Nutrition, Guangdong Engineering Technology Research Center of Animal Meat quality and Safety Control and Evaluation, Guangzhou, Guangdong, China
| | - Zhichang Liu
- Institute of Animal Science, Guangdong Academy of Agricultural Sciences, State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture, Guangdong Key Laboratory of Animal Breeding and Nutrition, Guangdong Engineering Technology Research Center of Animal Meat quality and Safety Control and Evaluation, Guangzhou, Guangdong, China
| | - Fengyin Wang
- Guangzhou AnRuiJie Environmental Protection Technology Co., Ltd., Guangzhou, China
| | - Xianyong Ma
- Institute of Animal Science, Guangdong Academy of Agricultural Sciences, State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture, Guangdong Key Laboratory of Animal Breeding and Nutrition, Guangdong Engineering Technology Research Center of Animal Meat quality and Safety Control and Evaluation, Guangzhou, Guangdong, China
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Le Beyec J, Billiauws L, Bado A, Joly F, Le Gall M. Short Bowel Syndrome: A Paradigm for Intestinal Adaptation to Nutrition? Annu Rev Nutr 2020; 40:299-321. [PMID: 32631145 DOI: 10.1146/annurev-nutr-011720-122203] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Short bowel syndrome (SBS) is a rare disease that results from extensive resection of the intestine. When the remaining absorption surface of the intestine cannot absorb enough macronutrients, micronutrients, and water, SBS results in intestinal failure (IF). Patients with SBS who suffer from IF require parenteral nutrition for survival, but long-term parenteral nutrition may lead to complications such as catheter sepsis and metabolic diseases. Spontaneous intestinal adaptation occurs weeks to months after resection, resulting in hyperplasia of the remnant gut, modification of gut hormone levels, dysbiosis, and hyperphagia. Oral nutrition and presence of the colon are two major positive drivers for this adaptation. This review aims to summarize the current knowledge of the mechanisms underlying spontaneous intestinal adaptation, particularly in response to modifications of luminal content, including nutrients. In the future, dietary manipulations could be used to treat SBS.
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Affiliation(s)
- Johanne Le Beyec
- Centre de Recherche sur l'Inflammation, INSERM UMRS-1149, Assistance Publique-Hôpitaux de Paris, Université de Paris, 75018 Paris, France; .,Service de Biochimie Endocrinienne et Oncologique, Hôpital Pitié-Salpêtrière-Charles Foix, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, 75013 Paris, France
| | - Lore Billiauws
- Centre de Recherche sur l'Inflammation, INSERM UMRS-1149, Assistance Publique-Hôpitaux de Paris, Université de Paris, 75018 Paris, France; .,Service de Gastroentérologie, MICI et Assistance Nutritive, Groupe Hospitalier Universitaire Paris Nord Val de Seine (GHUPNVS), Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Université de Paris, 92110 Clichy, France
| | - André Bado
- Centre de Recherche sur l'Inflammation, INSERM UMRS-1149, Assistance Publique-Hôpitaux de Paris, Université de Paris, 75018 Paris, France;
| | - Francisca Joly
- Centre de Recherche sur l'Inflammation, INSERM UMRS-1149, Assistance Publique-Hôpitaux de Paris, Université de Paris, 75018 Paris, France; .,Service de Gastroentérologie, MICI et Assistance Nutritive, Groupe Hospitalier Universitaire Paris Nord Val de Seine (GHUPNVS), Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Université de Paris, 92110 Clichy, France
| | - Maude Le Gall
- Centre de Recherche sur l'Inflammation, INSERM UMRS-1149, Assistance Publique-Hôpitaux de Paris, Université de Paris, 75018 Paris, France;
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Ou J, Courtney CM, Steinberger AE, Tecos ME, Warner BW. Nutrition in Necrotizing Enterocolitis and Following Intestinal Resection. Nutrients 2020; 12:nu12020520. [PMID: 32085587 PMCID: PMC7071274 DOI: 10.3390/nu12020520] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 02/13/2020] [Accepted: 02/14/2020] [Indexed: 12/25/2022] Open
Abstract
This review aims to discuss the role of nutrition and feeding practices in necrotizing enterocolitis (NEC), NEC prevention, and its complications, including surgical treatment. A thorough PubMed search was performed with a focus on meta-analyses and randomized controlled trials when available. There are several variables in nutrition and the feeding of preterm infants with the intention of preventing necrotizing enterocolitis (NEC). Starting feeds later rather than earlier, advancing feeds slowly and continuous feeds have not been shown to prevent NEC and breast milk remains the only effective prevention strategy. The lack of medical treatment options for NEC often leads to disease progression requiring surgical resection. Following resection, intestinal adaptation occurs, during which villi lengthen and crypts deepen to increase the functional capacity of remaining bowel. The effect of macronutrients on intestinal adaptation has been extensively studied in animal models. Clinically, the length and portion of intestine that is resected may lead to patients requiring parenteral nutrition, which is also reviewed here. There remain significant gaps in knowledge surrounding many of the nutritional aspects of NEC and more research is needed to determine optimal feeding approaches to prevent NEC, particularly in infants younger than 28 weeks and <1000 grams. Additional research is also needed to identify biomarkers reflecting intestinal recovery following NEC diagnosis individualize when feedings should be safely resumed for each patient.
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Affiliation(s)
- Jocelyn Ou
- Department of Pediatrics, Division of Newborn Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA;
| | - Cathleen M. Courtney
- Department of Surgery, Division of Pediatric Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; (C.M.C.); (A.E.S.); (M.E.T.)
| | - Allie E. Steinberger
- Department of Surgery, Division of Pediatric Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; (C.M.C.); (A.E.S.); (M.E.T.)
| | - Maria E. Tecos
- Department of Surgery, Division of Pediatric Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; (C.M.C.); (A.E.S.); (M.E.T.)
| | - Brad W. Warner
- Department of Surgery, Division of Pediatric Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; (C.M.C.); (A.E.S.); (M.E.T.)
- Correspondence: ; Tel.: 314-454-6022
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Burrin D, Sangild PT, Stoll B, Thymann T, Buddington R, Marini J, Olutoye O, Shulman RJ. Translational Advances in Pediatric Nutrition and Gastroenterology: New Insights from Pig Models. Annu Rev Anim Biosci 2020; 8:321-354. [PMID: 32069436 DOI: 10.1146/annurev-animal-020518-115142] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Pigs are increasingly important animals for modeling human pediatric nutrition and gastroenterology and complementing mechanistic studies in rodents. The comparative advantages in size and physiology of the neonatal pig have led to new translational and clinically relevant models of important diseases of the gastrointestinal tract and liver in premature infants. Studies in pigs have established the essential roles of prematurity, microbial colonization, and enteral nutrition in the pathogenesis of necrotizing enterocolitis. Studies in neonatal pigs have demonstrated the intestinal trophic effects of akey gut hormone, glucagon-like peptide 2 (GLP-2), and its role in the intestinal adaptation process and efficacy in the treatment of short bowel syndrome. Further, pigs have been instrumental in elucidating the physiology of parenteral nutrition-associated liver disease and the means by which phytosterols, fibroblast growth factor 19, and a new generation of lipid emulsions may modify disease. The premature pig will continue to be a valuable model in the development of optimal infant diets (donor human milk, colostrum), specific milk bioactives (arginine, growth factors), gut microbiota modifiers (pre-, pro-, and antibiotics), pharmaceutical drugs (GLP-2 analogs, FXR agonists), and novel diagnostic tools (near-infrared spectroscopy) to prevent and treat these pediatric diseases.
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Affiliation(s)
- Douglas Burrin
- USDA-ARS Children's Nutrition Research Center, Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Baylor College of Medicine, Houston, Texas 77030, USA;
| | - Per Torp Sangild
- Comparative Pediatrics and Nutrition, University of Copenhagen, DK-1870 Frederiksberg C., Copenhagen, Denmark
| | - Barbara Stoll
- USDA-ARS Children's Nutrition Research Center, Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Baylor College of Medicine, Houston, Texas 77030, USA;
| | - Thomas Thymann
- Comparative Pediatrics and Nutrition, University of Copenhagen, DK-1870 Frederiksberg C., Copenhagen, Denmark
| | - Randal Buddington
- College of Nursing, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
| | - Juan Marini
- USDA-ARS Children's Nutrition Research Center, Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Baylor College of Medicine, Houston, Texas 77030, USA;
- Department of Pediatrics, Section of Critical Care Medicine, Baylor College of Medicine, Houston, Texas 77030, USA
| | - Oluyinka Olutoye
- Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA
| | - Robert J Shulman
- USDA-ARS Children's Nutrition Research Center, Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Baylor College of Medicine, Houston, Texas 77030, USA;
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Moludi J, Maleki V, Jafari‐Vayghyan H, Vaghef‐Mehrabany E, Alizadeh M. Metabolic endotoxemia and cardiovascular disease: A systematic review about potential roles of prebiotics and probiotics. Clin Exp Pharmacol Physiol 2020; 47:927-939. [DOI: 10.1111/1440-1681.13250] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Revised: 12/28/2019] [Accepted: 12/31/2019] [Indexed: 12/31/2022]
Affiliation(s)
- Jalal Moludi
- School of Nutrition Sciences and Food Technology Kermanshah University of Medical Sciences Kermanshah Iran
- Clinical Research Development Center Imam Reza Hospital Kermanshah University of Medical Sciences Kermanshah Iran
| | - Vahid Maleki
- Student Research Committee Tabriz University of Medical Sciences Tabriz Iran
| | | | - Elnaz Vaghef‐Mehrabany
- Nutrition Research Center Faculty of Nutrition Tabriz University of Medical Sciences Tabriz Iran
| | - Mohammad Alizadeh
- Nutrition Research Center Faculty of Nutrition Tabriz University of Medical Sciences Tabriz Iran
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Propionate promotes vitamin D receptor expression via yes-associated protein in rats with short bowel syndrome. Biochem Biophys Res Commun 2020; 523:645-650. [PMID: 31941599 DOI: 10.1016/j.bbrc.2019.12.127] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Accepted: 12/19/2019] [Indexed: 11/20/2022]
Abstract
Vitamin D deficiency and refractory osteoporosis are common complications in patients with short bowel syndrome (SBS). The symptom of bone loss is not effectively alleviated, even after the oral administration of vitamin D in SBS patients who had been weaned off parenteral nutrition. In this study, we aimed to investigate the effect of propionate on the expression of the vitamin D receptor (VDR) in the small intestine of rats with SBS. Firstly, IEC-6 (intestinal epithelioid cell line No. 6) cells were incubated in vitro with 1 mM sodium propionate for 24 h. This resulted in a significant increase in the expression of VDR and yes-associated protein (YAP) compared with that in the control group. Transfection of IEC-6 cells with YAP siRNA significantly down-regulated the expression of VDR. By contrast, after incubating IEC-6 cells with lysophosphatidic acid, an agonist of YAP, upregulation of VDR and YAP was observed. Next, we investigated whether this effect occurs in vivo. Five-week-old male Sprague-Dawley rats underwent 80% small bowel resection to establish an SBS model. Rats treated with 1% w/v sodium propionate had high levels of VDR and YAP expression in the intestine and intestinal adaptation was clearly observed compared to the control group. However, these effects were blocked by intraperitoneal injection of verteporfin. Thus, this study showed that propionate promoted VDR expression in the intestine via the activity of YAP, both in vitro and in vivo. Moreover, propionate was shown to play an active role in postoperative intestinal adaptation in SBS rats.
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Wang H, Ren E, Xiang X, Su Y, Zhu W. Dynamic Changes in Serum Metabolomic Profiles of Growing Pigs Induced by Intravenous Infusion of Sodium Butyrate. Metabolites 2020; 10:metabo10010020. [PMID: 31906303 PMCID: PMC7023161 DOI: 10.3390/metabo10010020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Revised: 12/28/2019] [Accepted: 12/29/2019] [Indexed: 12/13/2022] Open
Abstract
This study aimed to explore the dynamic changes in metabolite profiles and metabolism pathways in the serum of growing pigs by intravenous infusion of sodium butyrate (SB). Fourteen crossbred growing barrows (BW = 23.70 ± 1.29 kg) fitted with jugular cannula were randomly allocated to the SB and control (Con) groups, each group consisted of seven replicates (pens), with one pig per pen. At 9:00 of each day during the experimental period, pigs in the SB group were infused with 10 mL of SB (200 mmol/L, pH 7.4, 37 °C) via precaval vein, while the Con group was treated with the same volume of physiological saline. On day 4, the blood of each pig was collected at 0, 30, 60, and 120 min after the intravenous infusion. Metabolites in the serum were detected by gas chromatograph-mass spectrometry analysis. Pathway analysis of metabolomic profiles showed that the differential metabolites mainly enriched in amino acid metabolism, lipid-related metabolism, and the tricarboxylic acid (TCA) cycle. More importantly, the relative concentrations of all eight essential amino acids, five non-essential amino acids, and two amino acid derivatives were decreased by the parenteral SB. In addition, SB significantly increased the relative concentrations of eicosanoic acid and octadecanoic acid and decreased the relative concentration of glycerol-3-phosphate at 0 min (three days after intravenous infusion of SB), which suggests that parenteral SB may increase stearates mobilization and decrease the biosynthesis of stearates. In conclusion, intravenous infusion of SB may induce more amino acids to synthesize proteins and affect fat metabolism through increasing fat mobilization and decreasing the biosynthesis of stearates. However, a further study is needed to understand the mechanism of extensive metabolic pathway changes induced by parenteral SB.
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Affiliation(s)
- Hongyu Wang
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China; (H.W.); (E.R.); (W.Z.)
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Erdu Ren
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China; (H.W.); (E.R.); (W.Z.)
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Xiaoe Xiang
- National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing 210095, China;
| | - Yong Su
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China; (H.W.); (E.R.); (W.Z.)
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
- Correspondence: ; Tel.: +86-25-84395523
| | - Weiyun Zhu
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China; (H.W.); (E.R.); (W.Z.)
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
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Dowhaniuk JK, Szamosi J, Chorlton S, Owens J, Mileski H, Clause R, Pernica JM, Bowdish DME, Surette MG, Ratcliffe EM. Starving the Gut: A Deficit of Butyrate in the Intestinal Ecosystem of Children With Intestinal Failure. JPEN J Parenter Enteral Nutr 2019; 44:1112-1123. [DOI: 10.1002/jpen.1715] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 08/25/2019] [Accepted: 09/08/2019] [Indexed: 12/14/2022]
Affiliation(s)
| | - Jake Szamosi
- Department of Medicine and Biochemistry and Biomedical SciencesMcMaster University Hamilton Ontario Canada
| | - Sam Chorlton
- Department of Undergraduate MedicineMcMaster University Hamilton Ontario Canada
| | - Jillian Owens
- Division of Pediatric Gastroenterology and NutritionMcMaster Children's Hospital Hamilton Ontario Canada
| | - Heather Mileski
- Division of Pediatric Gastroenterology and NutritionMcMaster Children's Hospital Hamilton Ontario Canada
| | - Rose‐Frances Clause
- Division of Pediatric Gastroenterology and NutritionMcMaster Children's Hospital Hamilton Ontario Canada
| | | | - Dawn M. E. Bowdish
- Department of Pathology & Molecular MedicineMcMaster University Hamilton Ontario Canada
| | - Michael G. Surette
- Department of Medicine and Biochemistry and Biomedical SciencesMcMaster University Hamilton Ontario Canada
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Importance of release location on the mode of action of butyrate derivatives in the avian gastrointestinal tract. WORLD POULTRY SCI J 2019. [DOI: 10.1017/s004393391500269x] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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40
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Knackstedt R, Knackstedt T, Gatherwright J. The role of topical probiotics in skin conditions: A systematic review of animal and human studies and implications for future therapies. Exp Dermatol 2019; 29:15-21. [DOI: 10.1111/exd.14032] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 07/27/2019] [Accepted: 08/26/2019] [Indexed: 02/06/2023]
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Goulet O, Abi Nader E, Pigneur B, Lambe C. Short Bowel Syndrome as the Leading Cause of Intestinal Failure in Early Life: Some Insights into the Management. Pediatr Gastroenterol Hepatol Nutr 2019; 22:303-329. [PMID: 31338307 PMCID: PMC6629594 DOI: 10.5223/pghn.2019.22.4.303] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Accepted: 05/11/2019] [Indexed: 12/13/2022] Open
Abstract
Intestinal failure (IF) is the critical reduction of the gut mass or its function below the minimum needed to absorb nutrients and fluids required for adequate growth in children. Severe IF requires parenteral nutrition (PN). Pediatric IF is most commonly due to congenital or neonatal intestinal diseases or malformations divided into 3 groups: 1) reduced intestinal length and consequently reduced absorptive surface, such as in short bowel syndrome (SBS) or extensive aganglionosis; 2) abnormal development of the intestinal mucosa such as congenital diseases of enterocyte development; 3) extensive motility dysfunction such as chronic intestinal pseudo-obstruction syndromes. The leading cause of IF in childhood is the SBS. In clinical practice the degree of IF may be indirectly measured by the level of PN required for normal or catch up growth. Other indicators such as serum citrulline have not proven to be highly reliable prognostic factors in children. The last decades have allowed the development of highly sophisticated nutrient solutions consisting of optimal combinations of macronutrients and micronutrients as well as guidelines, promoting PN as a safe and efficient feeding technique. However, IF that requires long-term PN may be associated with various complications including infections, growth failure, metabolic disorders, and bone disease. IF Associated Liver Disease may be a limiting factor. However, changes in the global management of IF pediatric patients, especially since the setup of intestinal rehabilitation centres did change the prognosis thus limiting "nutritional failure" which is considered as a major indication for intestinal transplantation (ITx) or combined liver-ITx.
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Affiliation(s)
- Olivier Goulet
- Department of Pediatric Gastroenterology-Hepatology-Nutrition, National Reference Center for Rare Digestive Diseases, Pediatric Intestinal Failure Rehabilitation Center, Hôpital Necker-Enfants Malades, University Sorbonne-Paris-Cité Paris Descartes Medical School, Paris, France
| | - Elie Abi Nader
- Department of Pediatric Gastroenterology-Hepatology-Nutrition, National Reference Center for Rare Digestive Diseases, Pediatric Intestinal Failure Rehabilitation Center, Hôpital Necker-Enfants Malades, University Sorbonne-Paris-Cité Paris Descartes Medical School, Paris, France
| | - Bénédicte Pigneur
- Department of Pediatric Gastroenterology-Hepatology-Nutrition, National Reference Center for Rare Digestive Diseases, Pediatric Intestinal Failure Rehabilitation Center, Hôpital Necker-Enfants Malades, University Sorbonne-Paris-Cité Paris Descartes Medical School, Paris, France
| | - Cécile Lambe
- Department of Pediatric Gastroenterology-Hepatology-Nutrition, National Reference Center for Rare Digestive Diseases, Pediatric Intestinal Failure Rehabilitation Center, Hôpital Necker-Enfants Malades, University Sorbonne-Paris-Cité Paris Descartes Medical School, Paris, France
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Lin S, Stoll B, Robinson J, Pastor JJ, Marini JC, Ipharraguerre IR, Hartmann B, Holst JJ, Cruz S, Lau P, Olutoye O, Fang Z, Burrin DG. Differential action of TGR5 agonists on GLP-2 secretion and promotion of intestinal adaptation in a piglet short bowel model. Am J Physiol Gastrointest Liver Physiol 2019; 316:G641-G652. [PMID: 30920308 PMCID: PMC6580240 DOI: 10.1152/ajpgi.00360.2018] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 03/14/2019] [Accepted: 03/20/2019] [Indexed: 02/06/2023]
Abstract
Enteroendocrine L cells and glucagon-like peptide 2 (GLP-2) secretion are activated in the intestinal adaptation process following bowel resection in patients with short bowel syndrome. We hypothesized that enteral activation of Takeda G protein-coupled receptor 5 (TGR5), expressed in enteroendocrine L cells, could augment endogenous GLP-2 secretion and the intestinal adaptation response. Our aim was to assess the efficacy of different TGR5 agonists to stimulate GLP-2 secretion and intestinal adaptation in a piglet short-bowel model. In study 1, parenterally fed neonatal pigs (n = 6/group) were gavaged with vehicle, olive extract (OE; 10 or 50 mg/kg), or ursolic acid (UA; 10 mg/kg), and plasma GLP-2 was measured for 6 h. In study 2, neonatal pigs (n = 6-8/group) were subjected to transection or 80% mid-small intestine resection and, after 2 days, assigned to treatments for 10 days as follows: 1) transection + vehicle (sham), 2) resection + vehicle (SBS), 3) resection + 30 mg UA (SBS + UA), and 4) resection + 180 mg/kg OE (SBS + OE). We measured plasma GLP-2, intestinal histology, cell proliferation, and gene expression, as well as whole body citrulline-arginine kinetics and bile acid profiles. In study 1, GLP-2 secretion was increased by UA and tended to be increased by OE. In study 2, SBS alone, but not additional treatment with either TGR5 agonist, resulted in increased mucosal thickness and crypt cell proliferation in remnant jejunum and ileum sections. SBS increased biliary and ileal concentration of bile acids and expression of inflammatory and farnesoid X receptor target genes, but these measures were suppressed by UA treatment. In conclusion, UA is an effective oral GLP-2 secretagogue in parenterally fed pigs but is not capable of augmenting GLP-2 secretion or the intestinal adaptation response after massive small bowel resection. NEW & NOTEWORTHY Therapeutic activation of endogenous glucagon-like peptide 2 (GLP-2) secretion is a promising strategy to improve intestinal adaptation in patients with short bowel syndrome. This study in neonatal pigs showed that oral supplementation with a selective Takeda G protein-coupled receptor 5 (TGR5) agonist is an effective approach to increase GLP-2 secretion. The results warrant further study to establish a more potent oral TGR5 agonist that can effectively improve intestinal adaptation in pediatric patients with SBS.
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Affiliation(s)
- Sen Lin
- Institute of Animal Nutrition, Sichuan Agricultural University , Chengdu, Sichuan , People's Republic of China
| | - Barbara Stoll
- US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center , Houston, Texas
| | - Jason Robinson
- US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center , Houston, Texas
| | | | - Juan C Marini
- US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center , Houston, Texas
- Section of Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine , Houston, Texas
| | - Ignacio R Ipharraguerre
- Lucta S.A., Montornès del Vallès, Spain
- Institute of Human Nutrition and Food Science, University of Kiel , Kiel , Germany
| | - Bolette Hartmann
- Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen , Copenhagen , Denmark
| | - Jens J Holst
- Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen , Copenhagen , Denmark
| | - Stephanie Cruz
- Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Texas Children's Hospital , Houston, Texas
| | - Patricio Lau
- Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Texas Children's Hospital , Houston, Texas
| | - Oluyinka Olutoye
- Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Texas Children's Hospital , Houston, Texas
| | - Zhengfeng Fang
- Institute of Animal Nutrition, Sichuan Agricultural University , Chengdu, Sichuan , People's Republic of China
| | - Douglas G Burrin
- US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center , Houston, Texas
- Section of Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Houston, Texas
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Norsa L, Lambe C, Abi Abboud S, Barbot-Trystram L, Ferrari A, Talbotec C, Kapel N, Pigneur B, Goulet O. The colon as an energy salvage organ for children with short bowel syndrome. Am J Clin Nutr 2019; 109:1112-1118. [PMID: 30924493 DOI: 10.1093/ajcn/nqy367] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Accepted: 12/03/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The main cause of intestinal failure is short bowel syndrome (SBS). The management goal for children with SBS is to promote intestinal adaptation while preserving growth and development with the use of parenteral nutrition (PN). OBJECTIVES This study evaluated the intestinal absorption rate in children with SBS, focusing on the role of the remnant colon. In addition, the relation between intestinal absorption rate, citrulline concentration, and small bowel length was studied. METHODS Thirty-two children with SBS on PN were included. They were divided into 3 groups according to the European Society for Clinical Nutrition and Metabolism (ESPEN) anatomical classification system: type 1 SBS (n = 9), type 2 (n = 13), and type 3 (n = 10). Intestinal absorption rate was assessed by a stool balance analysis of a 3-d collection of stools. Plasma citrulline concentrations were measured and the level of PN dependency was calculated. RESULTS The total energy absorption rate did not differ significantly between the 3 groups: 68% (61-79% ) for type 1, 60% (40-77%) for type 2, and 60% (40-77%) for type 3 ( P = 0.45). Children with type 2 or 3 SBS had significantly shorter small bowel length than children with type 1: 28 cm (19-36 cm) and 16 cm (2-29 cm), respectively, compared with 60 cm (45-78 cm) ( P = 0.04). Plasma citrulline concentrations were lower in type 3 SBS but not significantly different: 15 µmol/L (11-25 µmol/L) in type 1, 14 µmol/L (7-21 µmol/L) in type 2 , and 9 µmol/L (6-14 µmol/L) in type 3 ( P = 0.141). A multivariate analysis confirmed the role of the remnant colon in providing additional energy absorption. CONCLUSION This study demonstrated the importance of the colon as a salvage organ in children with SBS. Plasma citrulline concentrations should be interpreted according to the type of SBS. Efforts should focus on conservative surgery, early re-establishment of a colon in continuity, and preserving the intestinal microbiota.
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Affiliation(s)
- Lorenzo Norsa
- Department of Pediatric Gastroenterology-Hepatology-Nutrition, Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France.,Pediatric Gastroenterology, Hepatology and Nutrition, Ospedale Papa Giovanni XXIII, Bergamo, Italy
| | - Cécile Lambe
- Department of Pediatric Gastroenterology-Hepatology-Nutrition, Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France
| | - Sabine Abi Abboud
- Department of Pediatric Gastroenterology-Hepatology-Nutrition, Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France
| | - Laurence Barbot-Trystram
- Department of Coprology, Assistance Publique-Hôpitaux de Paris, Hopital de la Pitié-Salpêtrière and Université Paris Descartes, Paris, France
| | - Alberto Ferrari
- FROM Research Foundation (Fondazione per la Ricerca Ospedale Maggiore), ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Cécile Talbotec
- Department of Pediatric Gastroenterology-Hepatology-Nutrition, Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France
| | - Nathalie Kapel
- Department of Coprology, Assistance Publique-Hôpitaux de Paris, Hopital de la Pitié-Salpêtrière and Université Paris Descartes, Paris, France
| | - Benedicte Pigneur
- Department of Pediatric Gastroenterology-Hepatology-Nutrition, Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France
| | - Olivier Goulet
- Department of Pediatric Gastroenterology-Hepatology-Nutrition, Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France
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A More Robust Gut Microbiota in Calorie-Restricted Mice Is Associated with Attenuated Intestinal Injury Caused by the Chemotherapy Drug Cyclophosphamide. mBio 2019; 10:mBio.02903-18. [PMID: 30862756 PMCID: PMC6414708 DOI: 10.1128/mbio.02903-18] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Improving the gut microbiota via calorie restriction is beneficial for human health. Our findings showed differential responses between calorie-restricted mice and ad libitum-fed mice. Compared with the ad libitum-fed mice, the calorie-restricted mice were less susceptible to cyclophosphamide side effects otherwise observed on the gut integrity and its microbiota. These results show the potential benefits of manipulating the gut microbiota with CR prior to cancer chemotherapy. Cyclophosphamide (CTX) is widely used in cancer chemotherapy, but it often induces mucositis, in which the disruption of the gut microbiota might play a pivotal role. Whether the manipulation of the gut microbiota can be used as a strategy to improve CTX-induced mucositis remains to be studied. Here we observed the effects of a 4-week calorie restriction (CR) on CTX-induced mucositis. Compared with ad libitum-fed mice, CR mice showed significantly less mucositis in response to CTX, including lower intestinal permeability, less bacterial translocation, higher number of epithelial stem cells, and less epithelium damage. CTX induced significant shifts of the gut microbiota of the gut microbiota in ad libitum-fed control mice. In contrast, CR mice showed no significant change in their gut microbiota in responding to CTX treatment. CR significantly enriched the gut microbiota in Lactobacillus and Lachnospiraceae which are known to mitigate inflammation and improve gut barrier function. These findings suggest that CR remodeled gut microbiota is more robust and may contribute to attenuate the side effects of cyclophosphamide, which supports the concept that cancer chemotherapy would benefit from strategies targeting the gut microbiota.
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Xiong X, Tan B, Song M, Ji P, Kim K, Yin Y, Liu Y. Nutritional Intervention for the Intestinal Development and Health of Weaned Pigs. Front Vet Sci 2019; 6:46. [PMID: 30847348 PMCID: PMC6393345 DOI: 10.3389/fvets.2019.00046] [Citation(s) in RCA: 116] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Accepted: 02/04/2019] [Indexed: 01/20/2023] Open
Abstract
Weaning imposes simultaneous stress, resulting in reduced feed intake, and growth rate, and increased morbidity and mortality of weaned pigs. Weaning impairs the intestinal integrity, disturbs digestive and absorptive capacity, and increases the intestinal oxidative stress, and susceptibility of diseases in piglets. The improvement of intestinal development and health is critically important for enhancing nutrient digestibility capacity and disease resistance of weaned pigs, therefore, increasing their survival rate at this most vulnerable stage, and overall productive performance during later stages. A healthy gut may include but not limited several important features: a healthy proliferation of intestinal epithelial cells, an integrated gut barrier function, a preferable or balanced gut microbiota, and a well-developed intestinal mucosa immunity. Burgeoning evidence suggested nutritional intervention are one of promising measures to enhance intestinal health of weaned pigs, although the exact protective mechanisms may vary and are still not completely understood. Previous research indicated that functional amino acids, such as arginine, cysteine, glutamine, or glutamate, may enhance intestinal mucosa immunity (i.e., increased sIgA secretion), reduce oxidative damage, stimulate proliferation of enterocytes, and enhance gut barrier function (i.e., enhanced expression of tight junction protein) of weaned pigs. A number of feed additives are marketed to assist in boosting intestinal immunity and regulating gut microbiota, therefore, reducing the negative impacts of weaning, and other environmental challenges on piglets. The promising results have been demonstrated in antimicrobial peptides, clays, direct-fed microbials, micro-minerals, milk components, oligosaccharides, organic acids, phytochemicals, and many other feed additives. This review summarizes our current understanding of nutritional intervention on intestinal health and development of weaned pigs and the importance of mechanistic studies focusing on this research area.
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Affiliation(s)
- Xia Xiong
- Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Bie Tan
- Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Minho Song
- Department of Animal Science and Biotechnology, Chungnam National University, Daejeon, South Korea
| | - Peng Ji
- Department of Nutrition, University of California, Davis, Davis, CA, United States
| | - Kwangwook Kim
- Department of Animal Science, University of California, Davis, Davis, CA, United States
| | - Yulong Yin
- Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Yanhong Liu
- Department of Animal Science, University of California, Davis, Davis, CA, United States
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Teresa C, Antonella D, de Ville de Goyet Jean. New Nutritional and Therapeutical Strategies of NEC. Curr Pediatr Rev 2019; 15:92-105. [PMID: 30868956 DOI: 10.2174/1573396315666190313164753] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 10/09/2018] [Accepted: 03/06/2019] [Indexed: 11/22/2022]
Abstract
Necrotizing enterocolitis (NEC) is an acquired severe disease of the digestive system affecting mostly premature babies, possibly fatal and frequently associated to systemic complications. Because of the severity of this condition and the possible long-term consequences on the child's development, many studies have aimed at preventing the occurrence of the primary events at the level of the bowel wall (ischemia and necrosis followed by sepsis) by modifying or manipulating the diet (breast milk versus formula) and/or the feeding pattern (time for initiation after birth, continuous versus bolus feeding, modulation of intake according clinical events). Feeding have been investigated so far in order to prevent NEC. However, currently well-established and shared clinical nutritional practices are not available in preventing NEC. Nutritional and surgical treatments of NEC are instead well defined. In selected cases surgery is a therapeutic option of NEC, requiring sometimes partial intestinal resection responsible for short bowel syndrome. In this paper we will investigate the available options for treating NEC according to the Walsh and Kliegman classification, focusing on feeding practices in managing short bowel syndrome that can complicate NEC. We will also analyze the proposed ways of preventing NEC.
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Affiliation(s)
- Capriati Teresa
- Artificial Nutrition in Pediatric Children's Hospital, Bambino Gesu, Rome, Italy
| | - Diamanti Antonella
- Artificial Nutrition in Pediatric Children's Hospital, Bambino Gesu, Rome, Italy
| | - de Ville de Goyet Jean
- Pediatric Department for the Treatment and Study of abdominal Disease and Abdominal Transplants, ISMETT-UPMC, Palermo, Italy
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Neelis E, Koning B, Rings E, Wijnen R, Nichols B, Hulst J, Gerasimidis K. The Gut Microbiome in Patients with Intestinal Failure: Current Evidence and Implications for Clinical Practice. JPEN J Parenter Enteral Nutr 2018; 43:194-205. [DOI: 10.1002/jpen.1423] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 06/12/2018] [Indexed: 12/12/2022]
Affiliation(s)
- Esther Neelis
- Department of Paediatric GastroenterologyErasmus MC–Sophia Children's Hospital Rotterdam the Netherlands
| | - Barbara Koning
- Department of Paediatric GastroenterologyErasmus MC–Sophia Children's Hospital Rotterdam the Netherlands
| | - Edmond Rings
- Department of Paediatric GastroenterologyErasmus MC–Sophia Children's Hospital Rotterdam the Netherlands
- Paediatric GastroenterologyLeiden University Medical Center–Willem Alexander Children's Hospital Leiden the Netherlands
| | - René Wijnen
- Paediatric SurgeryErasmus MC–Sophia Children's Hospital Rotterdam the Netherlands
| | - Ben Nichols
- Human NutritionSchool of MedicineCollege of MedicineVeterinary and Life SciencesUniversity of Glasgow Glasgow United Kingdom
| | - Jessie Hulst
- Department of Paediatric GastroenterologyErasmus MC–Sophia Children's Hospital Rotterdam the Netherlands
| | - Konstantinos Gerasimidis
- Human NutritionSchool of MedicineCollege of MedicineVeterinary and Life SciencesUniversity of Glasgow Glasgow United Kingdom
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Chen X, Xu J, Su Y, Zhu W. Effects of Intravenous Infusion With Sodium Butyrate on Colonic Microbiota, Intestinal Development- and Mucosal Immune-Related Gene Expression in Normal Growing Pigs. Front Microbiol 2018; 9:1652. [PMID: 30079060 PMCID: PMC6062594 DOI: 10.3389/fmicb.2018.01652] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 07/02/2018] [Indexed: 12/21/2022] Open
Abstract
This study aimed to investigate effects of intravenous infusion with sodium butyrate (SB) on colonic microbiota, intestinal mucosal immune and intestinal development in normal growing pigs. Twelve crossbred barrows (Duroc × Landrace × Large White) fitted with a medical polyethylene cannula via internal jugular vein were daily infused with 10 ml SB (200 mmol/l) or the same volume of physiological saline for 7 days. Results showed that SB infusion had no effects on the short-chain fatty acids concentrations and the number of total bacteria, but significantly increased the microbial richness estimators (ACE and Chao1), and the abundance of genera related to Clostridiales order in the colonic digesta (P < 0.05). SB infusion significantly up-regulated the mRNA expression of monocarboxylate transporter 1 (MCT1) in the colon, while no change was found in the ileum. Only the relative mRNA of pro-inflammatory cytokine IL-6 gene was decreased significantly in the ileum by SB infusion. On the contrary, in the colon, SB infusion significantly decreased the gene expression of histone deacetylase 1 (HDAC1) and pro-inflammatory cytokines IL-6, IL-18, IL-12p40, and TNF-α (P < 0.05), but significantly increased the secretory immunoglobulin A (sIgA) concentration, the gene expression of anti-inflammatory cytokine IL-10, and the expression of intestinal development-related gene zonula occludens-1 (ZO-1), occludin, and epidermal growth factor (EGF) (P < 0.05). The results suggest that systemic SB can modify colonic microbial composition, regulate the inflammatory cytokine- and intestinal development-related gene expression in pigs under the normal physiological condition. This study may provide an alternative strategy for improving the intestinal health of normal piglets.
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Affiliation(s)
| | | | - Yong Su
- Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
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Abstract
Short-bowel syndrome represents the most common cause of intestinal failure and occurs when the remaining intestine cannot support fluid and nutrient needs to sustain adequate physiology and development without the use of supplemental parenteral nutrition. After intestinal loss or damage, the remnant bowel undergoes multifactorial compensatory processes, termed adaptation, which are largely driven by intraluminal nutrient exposure. Previous studies have provided insight into the biological processes and mediators after resection, however, there still remains a gap in the knowledge of more comprehensive mechanisms that drive the adaptive responses in these patients. Recent data support the microbiota as a key mediator of gut homeostasis and a potential driver of metabolism and immunomodulation after intestinal loss. In this review, we summarize the emerging ideas related to host-microbiota interactions in the intestinal adaptation processes.
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Key Words
- Adaptive Responses
- CONV, conventional
- ENS, enteric nervous system
- Enteric Flora
- GF, germ-free
- GI, gastrointestinal
- GLP-2, glucagon-like peptide 2
- IBD, inflammatory bowel disease
- ICR, ileocecal resection
- IF, intestinal failure
- IL, interleukin
- Immune System
- Intestinal Failure
- Microbial Metabolites
- NEC, necrotizing enterocolitis
- PN, parenteral nutrition
- SBR, small bowel resection
- SBS, short-bowel syndrome
- SCFA, short-chain fatty acid
- SFB, segmented filamentous bacteria
- TGR5, Takeda-G-protein-receptor 5
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