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Mazzuoli S, Regano N, Lamacchia S, Silvestri A, Guglielmi FW. Forty-eight months outcomes of teduglutide treatment in adult stable patients with short bowel syndrome and home parenteral nutrition dependence: A real-world Italian single-center observational cohort study. Nutrition 2025; 131:112640. [PMID: 39689615 DOI: 10.1016/j.nut.2024.112640] [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: 05/26/2024] [Revised: 10/24/2024] [Accepted: 11/10/2024] [Indexed: 12/19/2024]
Abstract
AIM OF THE STUDY This real-life study is designed to investigate the short and long-term efficacy and safety of teduglutide (TED) and its effects on the quality of life (QoL) in a cohort of adult, stable patients with short bowel syndrome and chronic intestinal failure receiving long-term parenteral support (PS). PATIENT AND METHODS A prospective, single-center study was conducted for individuals who began to take TED between March 2017 and August 2023. RESULTS Ten patients were included in the analysis, among whom the median duration of TED administration was 48 (range, 12-71) months. Data relative to short-term clinical outcomes demonstrate that 4 of 10 (40%) patients were early responders to TED therapy, defined as a >20% reduction in PS requirement at 3 months. Six of the 10 (60%) were non-responders. Data relative to 48 months long-term clinical outcomes demonstrated the absence of late responder patients and underline that all 4 early TED responder patients continued to maintain a sustained reduction in PS. Indeed, two of the 4 patients (50%) responding to TED discontinued PS while the other 2 patients (50%) reduced the number of weekly PS infusions by approximately 50%. The physical and mental components of the QoL improved significantly (P < 0.05) in responsive patients but did not change in non-responsive ones. Predictability of response to TED therapy in this study seemed to be linked to 1) SBS type 3, which was completely absent in the non-responder patients (P < 0.0001), 2) the residual small bowel length was significantly (P < 0.02) higher in responder (102 ± 18 cm) compared to non-responder patients (67 ± 27 cm), and 3) SBS type 1 and 2, enterostomy, surgical complications are significantly predictive of no response. Crohn's disease is equally present in both responder and non-responder patients. The number of side effects observed in our experience was extremely small both at the 3rd (0.01 n°/d/patients) and at the 48th month (0.001 n°/d/patients). No endoscopic neoplastic lesions were observed up to the 48th month of TED therapy. CONCLUSIONS This real-world experience allows us to state that, after 48 months of treatment, TED: 1) is a safe therapy with minimal, rare side effects; 2) produces a rapid reduction in PS volumes in 40% of treated patients; 3) consents 20% of enrolled patients to be weaned off PS; 4) maintains a stable nutritional state and, finally, 5) significantly improves the QoL.
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Affiliation(s)
- Silvia Mazzuoli
- Gastroenterology Department, Monsignor Raffaele DIMICCOLI Hospital, Barletta, BT, Italy
| | - Nunzia Regano
- Gastroenterology Department, Monsignor Raffaele DIMICCOLI Hospital, Barletta, BT, Italy
| | - Stefania Lamacchia
- Gastroenterology Department, Monsignor Raffaele DIMICCOLI Hospital, Barletta, BT, Italy
| | - Angela Silvestri
- Gastroenterology Department, Monsignor Raffaele DIMICCOLI Hospital, Barletta, BT, Italy
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Mihajlovic M, Rosseel Z, De Waele E, Vinken M. Parenteral nutrition-associated liver injury: clinical relevance and mechanistic insights. Toxicol Sci 2024; 199:1-11. [PMID: 38383052 DOI: 10.1093/toxsci/kfae020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/23/2024] Open
Abstract
Intestinal failure-associated liver disease (IFALD) is a relatively common complication in individuals receiving parenteral nutrition (PN). IFALD can be manifested as different types of liver injury, including steatosis, cholestasis, and fibrosis, and could result in liver failure in some cases. The onset and progression of IFALD are highly dependent on various patient and PN-related risk factors. Despite still being under investigation, several mechanisms have been proposed. Liver injury can originate due to caloric overload, nutrient deficiency, and toxicity, as well as phytosterol content, and omega-6 to omega-3 fatty acids ratio contained in lipid emulsions. Additional mechanisms include immature or defective bile acid metabolism, acute heart failure, infections, and sepsis exerting negative effects via Toll-like receptor 4 and nuclear factor κB inflammatory signaling. Furthermore, lack of enteral feeding, gut dysbiosis, and altered enterohepatic circulation that affect the farnesoid x receptor-fibroblast growth factor 19 axis can also contribute to IFALD. Various best practices can be adopted to minimize the risk of developing IFALD, such as prevention and management of central line infections and sepsis, preservation of intestine's length, a switch to oral and enteral feeding, cyclic PN, avoidance of overfeeding and soybean oil-based lipid formulations, and avoiding hepatotoxic substances. The present review thus provides a comprehensive overview of all relevant aspects inherent to IFALD. Further research focused on clinical observations, translational models, and advanced toxicological knowledge frameworks is needed to gain more insight into the molecular pathogenesis of hepatotoxicity, reduce IFALD incidence, and encourage the safe use of PN.
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Affiliation(s)
- Milos Mihajlovic
- Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium
| | - Zenzi Rosseel
- Department of Pharmacy, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium
- Department of Clinical Nutrition, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium
| | - Elisabeth De Waele
- Department of Clinical Nutrition, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium
- Department of Intensive Care, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium
- Faculty of Medicine and Pharmacy, Department of Clinical Sciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium
| | - Mathieu Vinken
- Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium
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Chowdhury F, Hill L, Shah N, Popov J, Cheveldayoff P, Pai N. Intestinal microbiome in short bowel syndrome: diagnostic and therapeutic opportunities. Curr Opin Gastroenterol 2023; 39:463-471. [PMID: 37751391 DOI: 10.1097/mog.0000000000000970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/28/2023]
Abstract
PURPOSE OF REVIEW The intestinal microbiome plays a strong, complementary role in the development and integrity of the intestinal epithelium. This biology is crucial for intestinal adaptation, particularly after the mucosal insults that lead to short bowel syndrome (SBS). The purpose of this review is to discuss relationships between the intestinal microbiota and the physiology of intestinal adaptation. RECENT FINDINGS We will address interactions between the intestinal microbiome and nutritional metabolism, factors leading to dysbiosis in SBS, and common compositional differences of the gut microbiome in SBS patients as compared to healthy controls. We will also discuss novel opportunities to expand diagnostic and therapeutic interventions in this population, by using our knowledge of the microbiome to manipulate luminal bacteria and study their resultant metabolites. As microbial therapeutics advance across so many fields of medicine, this review is timely in its advocacy for ongoing research that focuses on the SBS population.Our review will discuss 4 key areas: 1) physiology of the intestinal microbiome in SBS, 2) clinical and therapeutic insults that lead to a state of dysbiosis, 3) currently available evidence on microbiome-based approaches to SBS management, and 4) opportunities and innovations to inspire future research. SUMMARY The clinical implications of this review are both current, and potential. Understanding how the microbiome impacts intestinal adaptation and host physiology may enhance our understanding of why we experience such clinical variability in SBS patients' outcomes. This review may also expand clinicians' understanding of what 'personalized medicine' can mean for this patient population, and how we may someday consider our nutritional, therapeutic, and prognostic recommendations based on our patients' host, and microbial physiology.
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Affiliation(s)
- Fariha Chowdhury
- Department of Pediatrics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario
| | - Lee Hill
- Department of Pediatrics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario
- Department of Pediatrics, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
| | - Nyah Shah
- Department of Pediatrics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario
| | - Jelena Popov
- Harvard Medical School, Boston, Massachusetts, United States of America
| | - Paige Cheveldayoff
- Department of Pediatrics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario
- Centre for Metabolism, Obesity and Diabetes Research
| | - Nikhil Pai
- Department of Pediatrics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario
- Centre for Metabolism, Obesity and Diabetes Research
- Farncombe Family Digestive Health Research Institute, McMaster University
- Division of Pediatric Gastroenterology & Nutrition, McMaster Children's Hospital, Hamilton, Ontario, Canada
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Fourati S, de Dreuille B, Bettolo J, Hutinet C, Le Gall M, Bado A, Joly F, Le Beyec J. Hyperphagia is prominent in adult patients with short bowel syndrome: A role for the colon? Clin Nutr 2023; 42:2109-2115. [PMID: 37751660 DOI: 10.1016/j.clnu.2023.09.003] [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: 06/09/2023] [Revised: 08/24/2023] [Accepted: 09/03/2023] [Indexed: 09/28/2023]
Abstract
RATIONALE Short Bowel Syndrome (SBS) is the major cause of chronic intestinal failure (IF) and requires parenteral nutrition (PN). After bowel resection, some patients develop spontaneous intestinal adaptations and hyperphagia. Since promoting oral energy intake contributes to PN weaning, this study aims to characterize hyperphagia in patients with SBS and identify its determinants. METHODS This observational retrospective study included adult patients with SBS who were followed at an expert PN center between 2006 and 2019, with at least 2 separate nutritional assessments. Exclusion criteria were: active neoplasia, alternative treatment for IF or appetite-affecting medication. Resting energy expenditure (REE) was calculated for each patient using the Harris-Benedict equation. Food Intake Ratio (FIR) was calculated by dividing the highest caloric oral intake by REE and hyperphagia was defined as FIR >1.5. RESULTS Among the 59 patients with SBS included in this study, 82.6% had a FIR >1.5, including 15.5% with a FIR >3. Protein supplied approximately 16% of total energy intake while fat and carbohydrates provided 36% and 48%, respectively. The FIR was independent of gender and whether patients received oral nutrition alone (n = 28) or combined with PN (n = 31). The FIR was also not associated with residual small bowel length, nor the proportion of preserved colon. However, it was negatively correlated with the body mass index (BMI) of these patients (r = -0.533, p < 0.001), whether they had PN support or not. Patients with either a jejuno-colonic (n = 31) or a jejuno-ileal anastomosis (n = 9), had a significantly higher FIR compared to those with an end-jejunostomy (n = 18) (p < 0.05). However, no difference was found in the proportion of calories provided by protein, fat and carbohydrate between the 3 patients groups divided according to the SBS anatomical type. CONCLUSION A large majority of patients with SBS exhibited a hyperphagia regardless of PN dependence or bowel length, which was inversely correlated with BMI. The presence of the colon in continuity, thus in contact with the nutritional flow, seems to favor a higher oral intake which is beneficial for the nutritional autonomy of patients. This raises the question of a role of colonic microbiota and hormones in this behavior. Finally, this study also revealed an unexpected discrepancy between recommended energy intakes from protein, fat and carbohydrate and the actual intake of patients with SBS.
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Affiliation(s)
- Salma Fourati
- UMR-S 1149 Centre de Recherche sur l'Inflammation Inserm, Université Paris Cité, 75018 Paris, France; Service de Biochimie Endocrinienne et Oncologique, Hôpital de la Pitié-Salpêtrière-Charles Foix, Sorbonne Université, 75013 Paris, France.
| | - Brune de Dreuille
- UMR-S 1149 Centre de Recherche sur l'Inflammation Inserm, Université Paris Cité, 75018 Paris, France
| | - Joanna Bettolo
- Department of Gastroenterology and Nutritional Support, Center for Intestinal Failure, Reference Centre of Rare Disease MarDI, AP-HP Beaujon Hospital, University of Paris Inserm UMR 1149, Paris, France
| | - Coralie Hutinet
- Department of Gastroenterology and Nutritional Support, Center for Intestinal Failure, Reference Centre of Rare Disease MarDI, AP-HP Beaujon Hospital, University of Paris Inserm UMR 1149, Paris, France
| | - Maude Le Gall
- UMR-S 1149 Centre de Recherche sur l'Inflammation Inserm, Université Paris Cité, 75018 Paris, France
| | - André Bado
- UMR-S 1149 Centre de Recherche sur l'Inflammation Inserm, Université Paris Cité, 75018 Paris, France
| | - Francisca Joly
- UMR-S 1149 Centre de Recherche sur l'Inflammation Inserm, Université Paris Cité, 75018 Paris, France; Department of Gastroenterology and Nutritional Support, Center for Intestinal Failure, Reference Centre of Rare Disease MarDI, AP-HP Beaujon Hospital, University of Paris Inserm UMR 1149, Paris, France
| | - Johanne Le Beyec
- UMR-S 1149 Centre de Recherche sur l'Inflammation Inserm, Université Paris Cité, 75018 Paris, France; Service de Biochimie Endocrinienne et Oncologique, Hôpital de la Pitié-Salpêtrière-Charles Foix, Sorbonne Université, 75013 Paris, France
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Tappenden KA. Anatomical and physiological considerations in short bowel syndrome: Emphasis on intestinal adaptation and the role of enterohormones. Nutr Clin Pract 2023; 38 Suppl 1:S27-S34. [PMID: 37115026 DOI: 10.1002/ncp.10991] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 03/10/2023] [Accepted: 03/13/2023] [Indexed: 04/29/2023] Open
Abstract
Short bowel syndrome (SBS)-associated intestinal failure (IF) is a complex, life-threatening condition that requires complex care of multiple factors impacting the patient's long-term prognosis. Various etiologies result in SBS-IF, with three primary anatomical subtypes occurring following intestinal resection. Depending on the extent and segment(s) of the intestine resected, malabsorption can be nutrient specific or sweeping; however, such issues and the associated prognosis for the patient can be predicted with analysis of the residual intestine, along with baseline nutrient and fluid deficits and extent of malabsorption. The provision of parenteral nutrition/intravenous (PN-IV) fluids and antisymptomatic agents is fundamental; however, optimal management should focus on intestinal rehabilitation, wherein intestinal adaptation is prioritized and PN-IV fluids are weaned over time. Key strategies to maximize intestinal adaptation include hyperphagic consumption of an individualized SBS diet and the appropriate use of trophic agents, such as a glucagon-like peptide 2 analog.
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Affiliation(s)
- Kelly A Tappenden
- Department of Kinesiology and Nutrition, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, Illinois, USA
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The Role of a Colon-in-Continuity in Short Bowel Syndrome. Nutrients 2023; 15:nu15030628. [PMID: 36771335 PMCID: PMC9918966 DOI: 10.3390/nu15030628] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/11/2023] [Accepted: 01/20/2023] [Indexed: 01/28/2023] Open
Abstract
Short bowel syndrome (SBS) is a rare gastrointestinal condition that is defined as having less than 200 cm of remaining small intestine. SBS results from extensive surgical resection and is associated with a high risk for intestinal failure (IF) with a need for parenteral support (PS). Depending on the region of intestinal resection, three different main anatomy types can be distinguished from each other. In this review, we synthesize the current knowledge on the role of the colon in the setting of SBS-IF with a colon-in-continuity (SBS-IF-CiC), e.g., by enhancing the degree of intestinal adaptation, energy salvage, and the role of the microbiota. In addition, the effect of the disease-modifying treatment with glucagon-like peptide-2 (GLP-2) analogs in SBS-IF-CiC and how it differs from patients without a colon will be discussed. Overall, the findings explained in this review highlight the importance of preservation of the colon in SBS-IF.
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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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L’intestin un organe endocrine : de la physiologie aux implications thérapeutiques en nutrition. NUTR CLIN METAB 2022. [DOI: 10.1016/j.nupar.2021.12.179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Wang Y, Zheng L, Zhou Z, Yao D, Huang Y, Liu B, Duan Y, Li Y. Review article: insights into the bile acid-gut microbiota axis in intestinal failure-associated liver disease-redefining the treatment approach. Aliment Pharmacol Ther 2022; 55:49-63. [PMID: 34713470 DOI: 10.1111/apt.16676] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 06/04/2021] [Accepted: 10/15/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND Intestinal failure-associated liver disease (IFALD) increases mortality of patients with intestinal failure (IF), but lacks effective prevention or treatment approaches. Bile acids, gut microbiota and the host have close and complex interactions, which play a central role in modulating host immune and metabolic homeostasis. Increasing evidence suggests that derangement of the bile acid-gut microbiota (BA-GM) axis contributes to the development of IFALD. AIMS To review the BA-GM axis in the pathogenesis and clinical applications of IFALD, and to explore future directions for effective disease management. METHODS We conducted a literature search on bile acid and gut microbiota in IF and liver diseases. RESULTS The BA-GM axis demonstrates a unique IF signature manifesting as an increase in primary-to-secondary bile acids ratio, disturbed enterohepatic circulation, blunted bile acid signalling pathways, gut microbial dysbiosis, and altered microbial metabolic outputs. Bile acids and gut microbiota shape the compositional and functional alterations of each other in IF; collaboratively, they promote immune dysfunction and metabolic aberration in the liver. Diagnostic markers and treatments targeting the BA-GM axis showed promising potential in the management of IFALD. CONCLUSIONS Bile acids and gut microbiota play a central role in the development of IFALD and make attractive biomarkers as well as therapeutic targets. A multitarget, individualised therapy aiming at different parts of the BA-GM axis may provide optimal clinical benefits and requires future investigation.
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Affiliation(s)
- Yaoxuan Wang
- Department of General Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Lei Zheng
- Department of General Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Zhiyuan Zhou
- Department of General Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Danhua Yao
- Department of General Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Yuhua Huang
- Department of General Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Bin Liu
- Department of General Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Yantao Duan
- Department of General Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Yousheng Li
- Department of General Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
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Mazzuoli S, Regano N, Lamacchia S, Silvestri A, Guglielmi FW. Intestinal iatrogenic hyperadaptation in patients with short bowel syndrome and Crohn's disease: Is this an indication for mandatory lifelong injections of teduglutide? Nutrition 2021; 91-92:111396. [PMID: 34399400 DOI: 10.1016/j.nut.2021.111396] [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: 04/19/2021] [Revised: 05/20/2021] [Accepted: 06/16/2021] [Indexed: 11/18/2022]
Abstract
Short bowel syndrome with chronic intestinal failure (SBS-CIF) is a rare disease leading to a markedly decreased absorption of fluids and nutrients. Intestinal adaptation in patients with SBS-CIF who are treated with home parenteral nutrition is a natural repair process activated by increased secretions of glucagon-like peptide-2, inducing intestinal trophism, nutrient transport, and lowering gastrointestinal motility. Teduglutide (TED), a glucagon-like peptide-2 analog, offers a new, effective therapeutic alternative to boost intestinal adaptation. There is still no consensus regarding the question of whether intestinal adaptation is permanent or a transient, drug-dependent process requiring lifelong injections of TED. Here we report the clinical cases of two female patients with SBS-CIF secondary to Crohn's disease, who had received TED for 36 and 41 mo. In both patients, TED was discontinued for 5 d but needed to be resumed after an additional 5 d. In patient 1, the discontinuation of TED was accidental (the patient inadvertently injected frozen TED vials); whereas in patient 2, the suspension was at the patient's request. A rapid, significant (P < 0.0001) decline of intestinal function (diarrheal evacuations, fecal volume, food intake) was documented after the suspension of active TED in patient 1. After the resumption of active TED, the symptoms rapidly and significantly (P < 0.0001) improved. The same trend was observed in patient 2. Infective causes of diarrhea were ruled out in both patients. In conclusion, our experience shows that even after long-term treatment, the iatrogenic hyperadaptation process obtained with TED results is a temporary, drug-dependent process and vanishes with the suspension of therapy. These clinical cases suggest that in patients with SBS-CIF receiving TED, this treatment must be administered lifelong.
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Affiliation(s)
- Silvia Mazzuoli
- Gastroenterology Department, Monsignor Raffaele Dimiccoli Hospital, Barletta, Italy
| | - Nunzia Regano
- Gastroenterology Department, Monsignor Raffaele Dimiccoli Hospital, Barletta, Italy
| | - Stefania Lamacchia
- Gastroenterology Department, Monsignor Raffaele Dimiccoli Hospital, Barletta, Italy
| | - Angela Silvestri
- Gastroenterology Department, Monsignor Raffaele Dimiccoli Hospital, Barletta, Italy
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Neelis EG, de Koning BAE, Hulst JM, Papadopoulou R, Kerbiriou C, Rings EHHM, Wijnen RMH, Nichols B, Gerasimidis K. Gut microbiota and its diet-related activity in children with intestinal failure receiving long-term parenteral nutrition. JPEN J Parenter Enteral Nutr 2021; 46:693-708. [PMID: 33982321 PMCID: PMC9255855 DOI: 10.1002/jpen.2188] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Background This study characterized gut microbiota and its diet‐related activity in children with intestinal failure (IF) receiving parenteral nutrition (PN) compared with those of healthy controls (HC) and in relation to disease characteristics. Methods The fecal microbiota and short‐chain fatty acids (SCFAs) were measured in 15 IF patients (n = 68) and 25 HC (n = 25). Results Patients with IF had a lower bacterial load (P = .003), diversity (P < .001), evenness (P < .001) and richness (P = 0.006) than HC. Patients with surgical IF had lower diversity (P < .039) than those with functional IF. Propionic acid and butyric acid (p < .001) were lower and d‐lactate and l‐lactate were higher (p < 0.001) in IF patients than in HC. The energy supplied by PN (%PN) was negatively associated with microbiota diversity and SCFA profile. IF patients had more Escherichia‐Shigella (P = .006), Cronobacter (P = .001), and Staphylococcus (Operational Taxonomic Unit 14, P < .001) and less Faecalibacterium (P < 0.001) and Ruminococcus 1 and 2 (P < .001). Duration of PN (P = .005), %PN (P = .005), and fiber intake (P = .011) were predictive of microbiota structure. Higher intake of enteral nutrition was associated with microbiota structure and function closer to those of HC. Conclusions Microbiota composition and its diet‐related function are altered in IF, with depletion of beneficial SCFAs and species and supraphysiological increase of potentially harmful pathobionts. The influence of this compositional and functional microbial dysbiosis on patients’ outcomes and management warrants further exploration.
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Affiliation(s)
- Esther G Neelis
- Department of Pediatric Gastroenterology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Barbara A E de Koning
- Department of Pediatric Gastroenterology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Jessie M Hulst
- Department of Pediatric Gastroenterology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.,Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Rodanthi Papadopoulou
- Human Nutrition, School of Medicine, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
| | - Caroline Kerbiriou
- Human Nutrition, School of Medicine, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
| | - Edmond H H M Rings
- Department of Pediatric Gastroenterology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.,Department of Pediatric Gastroenterology, Leiden University Medical Center-Willem Alexander Children's Hospital, Leiden, The Netherlands
| | - René M H Wijnen
- Department of Pediatric Surgery, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Ben Nichols
- Department of Pediatric Gastroenterology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Konstantinos Gerasimidis
- Department of Pediatric Gastroenterology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands
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12
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Fousekis FS, Mitselos IV, Christodoulou DK. New insights into intestinal failure-associated liver disease in adults: A comprehensive review of the literature. Saudi J Gastroenterol 2021; 27:3-12. [PMID: 33642350 PMCID: PMC8083246 DOI: 10.4103/sjg.sjg_551_20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Intestinal failure-associated liver disease (IFALD) remains one of the most common and serious complications of parenteral nutrition (PN), causing a wide spectrum of hepatic manifestations from steatosis and mild cholestasis to portal hypertension and end-stage liver failure. The prevalence of IFALD depends on the diagnostic criteria and ranges from 4.3% to 65%. Moreover, many factors are shown to contribute to its development, including nutrient deficiencies, toxicity of PN, infections, and alterations of bile acid metabolism and gut microbiota. Prevention and management of IFALD aim at ameliorating or eliminating the risk factors associated with IFALD. The use of PN formulations with a lower ratio omega-6-to-omega-3 polyunsaturated fatty acids, cycle PN, optimization of enteral stimulation and prevention and early treatment of infections constitute the main therapeutic targets. However, failure of improvement and severe IFALD with end-stage liver failure should be considered as the indications of intestinal transplantation. The aim of this review is to provide an update of the epidemiology, pathophysiology, and diagnosis of IFALD in the adult population as well as to present a clinical approach of the therapeutic strategies of IFALD and present novel therapeutic targets.
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Affiliation(s)
- Fotios S. Fousekis
- Department of Gastroenterology and Hepatology, School of Health Sciences, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Ioannis V. Mitselos
- Department of Gastroenterology and Hepatology, School of Health Sciences, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Dimitrios K. Christodoulou
- Department of Gastroenterology and Hepatology, School of Health Sciences, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, Ioannina, Greece,Address for correspondence: Prof. Dimitrios K. Christodoulou, Professor of Gastroenterology, Department of Gastroenterology and Hepatology, School of Health Sciences, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, POBox 1186, Ioannina 45110, Greece. E-mail:
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13
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Abstract
PURPOSE OF REVIEW Since the approval of teduglutide, a glucagon-like peptide-2 (GLP-2) analog, for the treatment of patients with short bowel syndrome (SBS) associated with intestinal failure, enterohormone therapy has received significant interest and is becoming the first choice of treatment in selected patients. As such, it is paramount to assess and understand the new place of hormonal therapy in the algorithm of treatments in SBS-intestinal failure. RECENT FINDINGS Specialized intestinal failure units have recently reported their outcomes with teduglutide to evaluate if they are consistent with the phase III trials results. SBS-intestinal failure patients are very heterogenous including their response to this treatment, hence the importance of real-life studies beyond the context of clinical trials. Moreover, it is essential to find a consensus on criteria identifying candidate patients for teduglutide. In addition, the impact of teduglutide on quality of life and its cost-effectiveness are emerging as well as new enterohormone treatments are being studied whether it is long action GLP-2 analog or other ileocolonic break hormones like glucagon-like peptide-1 analog. SUMMARY Hormonotherapy is currently modifying the natural history of patients with SBS-intestinal failure by decreasing their need for parenteral support and possibly even complications associated with long-term parenteral support. Enterohormone treatment is now the cornerstone in SBS-intestinal failure and should be offered as a first-line therapy to selected patients.
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Affiliation(s)
- Dane Christina Daoud
- Division of Gastroenterology, Department of Medicine, Centre Hospitalier de l'Université de Montréal (CHUM), Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada
| | - Francisca Joly
- Department of Gastroenterology and Nutritional Support, Center for Intestinal Failure, Reference Centre of Rare Disease MarDI, AP-HP Beaujon Hospital, University of Paris Inserm UMR 1149, Paris, France
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14
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Abstract
Parenteral nutrition has been widely used in patients whose gastrointestinal tract is anatomically or physiologically unavailable for sufficient food intake. It has been considered lifesaving but is not without adverse effects. It has been proven to cause liver injury through different mechanisms. We present a review of parenteral nutrition-associated liver disease.
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15
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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: 22] [Impact Index Per Article: 4.4] [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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16
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Le Gall M, Thenet S, Aguanno D, Jarry AC, Genser L, Ribeiro-Parenti L, Joly F, Ledoux S, Bado A, Le Beyec J. Intestinal plasticity in response to nutrition and gastrointestinal surgery. Nutr Rev 2020; 77:129-143. [PMID: 30517714 DOI: 10.1093/nutrit/nuy064] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The plasticity of a material corresponds to its capacity to change its feature under the effect of an external action. Intestinal plasticity could be defined as the ability of the intestine to modify its size or thickness and intestinal cells to modulate their absorption and secretion functions in response to external or internal cues/signals. This review will focus on intestinal adaptation mechanisms in response to diet and nutritional status. These physiological mechanisms allow a fine and rapid adaptation of the gut to promote absorption of ingested food, but they can also lead to obesity in response to overnutrition. This plasticity could thus become a therapeutic target to treat not only undernutrition but also obesity. How the intestine adapts in response to 2 types of surgical remodeling of the digestive tract-extensive bowel resection leading to intestinal failure and surgical treatment of pathological obesity (ie, bariatric surgeries)-will also be reviewed.
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Affiliation(s)
- Maude Le Gall
- Centre de Recherche sur l'Inflammation, Inserm UMRS _1149, Université Paris Diderot, AP-HP, Paris, France
| | - Sophie Thenet
- Centre de Recherche des Cordeliers, Sorbonne Université, EPHE, PSL University, Sorbonne Cités, UPD Univ Paris 05, INSERM, CNRS, Paris, France
| | - Doriane Aguanno
- Centre de Recherche des Cordeliers, Sorbonne Université, EPHE, PSL University, Sorbonne Cités, UPD Univ Paris 05, INSERM, CNRS, Paris, France
| | - Anne-Charlotte Jarry
- Centre de Recherche sur l'Inflammation, Inserm UMRS _1149, Université Paris Diderot, AP-HP, Paris, France
| | - Laurent Genser
- Sorbonne Université, INSERM, Nutriomics Team, Paris, France, and the Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Department of Hepato-Biliary and Pancreatic Surgery, Liver Transplantation, Paris, France
| | - Lara Ribeiro-Parenti
- Centre de Recherche sur l'Inflammation, Inserm UMRS _1149, Université Paris Diderot, AP-HP, Paris, France.,Department of General and Digestive Surgery, University Hospital Bichat-Claude-Bernard, Paris, France
| | - Francisca Joly
- Centre de Recherche sur l'Inflammation, Inserm UMRS _1149, Université Paris Diderot, AP-HP, Paris, France.,Department of Gastroenterology, Inflammatory Bowel Diseases, Nutritional Support and Intestinal Transplantation, Paris, France
| | - Séverine Ledoux
- Centre de Recherche sur l'Inflammation, Inserm UMRS _1149, Université Paris Diderot, AP-HP, Paris, France.,Service des Explorations Fonctionnelles, Centre de référence de prise en charge de l'obésité, GHUPNVS, Hôpital Louis Mourier, Colombes, France
| | - André Bado
- Centre de Recherche sur l'Inflammation, Inserm UMRS _1149, Université Paris Diderot, AP-HP, Paris, France
| | - Johanne Le Beyec
- Centre de Recherche sur l'Inflammation, Inserm UMRS _1149, Université Paris Diderot, AP-HP, Paris, France.,Sorbonne Université, AP-HP, Hôpital Pitié-Salpêtrière-Charles Foix, Biochimie Endocrinienne et Oncologique, Paris, France
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17
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de Laffolie J, Sheridan D, Reinshagen K, Wessel L, Zimmermann C, Stricker S, Lerch MM, Weigel M, Hain T, Domann E, Rudloff S, Nichols BL, Naim HY, Zimmer KP. Digestive enzyme expression in the large intestine of children with short bowel syndrome in a late stage of adaptation. FASEB J 2020; 34:3983-3995. [PMID: 31957074 DOI: 10.1096/fj.201901758rr] [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: 07/13/2019] [Revised: 12/23/2019] [Accepted: 12/27/2019] [Indexed: 01/10/2023]
Abstract
BACKGROUND AND AIMS Intestinal adaptation in short bowel syndrome (SBS) includes morphologic processes and functional mechanisms. This study investigated whether digestive enzyme expression in the duodenum and colon is upregulated in SBS patients. METHOD Sucrase-isomaltase (SI), lactase-phlorizin hydrolase (LPH), and neutral Aminopeptidase N (ApN) were analyzed in duodenal and colonic biopsies from nine SBS patients in a late stage of adaptation as well as healthy and disease controls by immunoelectron microscopy (IEM), Western blots, and enzyme activities. Furthermore, proliferation rates and intestinal microbiota were analyzed in the mucosal specimen. RESULTS We found significantly increased amounts of SI, LPH, and ApN in colonocytes in most SBS patients with large variation and strongest effect for SI and ApN. Digestive enzyme expression was only partially elevated in duodenal enterocytes due to a low proliferation level measured by Ki-67 staining. Microbiome analysis revealed high amounts of Lactobacillus resp. low amounts of Proteobacteria in SBS patients with preservation of colon and ileocecal valve. Colonic expression was associated with a better clinical course in single cases. CONCLUSION In SBS patients disaccharidases and peptidases can be upregulated in the colon. Stimulation of this colonic intestinalization process by drugs, nutrients, and pre- or probiotics might offer better therapeutic approaches.
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Affiliation(s)
- Jan de Laffolie
- Department of Paediatrics, Justus-Liebig-University Giessen, Giessen, Germany
| | - Diana Sheridan
- Department of Pathology, Justus-Liebig-University Giessen, Giessen, Germany
| | - Konrad Reinshagen
- Department of Pediatric Surgery, UKE: University Hospital Eppendorf, Altona Children's Hospital, Hamburg, Germany
| | - Lucas Wessel
- Department of Pediatric Surgery, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany
| | | | - Sebastian Stricker
- Department of Paediatrics, Justus-Liebig-University Giessen, Giessen, Germany
| | - Markus M Lerch
- Department of Internal Medicine A, Ernst-Moritz-Arndt University, Greifswald, Germany
| | - Markus Weigel
- Institute of Medical Microbiology, Justus-Liebig-University Giessen, Giessen, Germany.,German Centre for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Justus Liebig University Giessen, Giessen, Germany
| | - Torsten Hain
- Institute of Medical Microbiology, Justus-Liebig-University Giessen, Giessen, Germany.,German Centre for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Justus Liebig University Giessen, Giessen, Germany
| | - Eugen Domann
- Institute of Medical Microbiology, Justus-Liebig-University Giessen, Giessen, Germany.,German Centre for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Justus Liebig University Giessen, Giessen, Germany
| | - Silvia Rudloff
- Department of Paediatrics, Justus-Liebig-University Giessen, Giessen, Germany
| | - Buford L Nichols
- Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA
| | - Hassan Y Naim
- Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Klaus-Peter Zimmer
- Department of Paediatrics, Justus-Liebig-University Giessen, Giessen, Germany
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18
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Camilleri M. Leaky gut: mechanisms, measurement and clinical implications in humans. Gut 2019; 68:1516-1526. [PMID: 31076401 PMCID: PMC6790068 DOI: 10.1136/gutjnl-2019-318427] [Citation(s) in RCA: 638] [Impact Index Per Article: 106.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Revised: 04/22/2019] [Accepted: 04/23/2019] [Indexed: 12/11/2022]
Abstract
The objectives of this review on 'leaky gut' for clinicians are to discuss the components of the intestinal barrier, the diverse measurements of intestinal permeability, their perturbation in non-inflammatory 'stressed states' and the impact of treatment with dietary factors. Information on 'healthy' or 'leaky' gut in the public domain requires confirmation before endorsing dietary exclusions, replacement with non-irritating foods (such as fermented foods) or use of supplements to repair the damage. The intestinal barrier includes surface mucus, epithelial layer and immune defences. Epithelial permeability results from increased paracellular transport, apoptosis or transcellular permeability. Barrier function can be tested in vivo using orally administered probe molecules or in vitro using mucosal biopsies from humans, exposing the colonic mucosa from rats or mice or cell layers to extracts of colonic mucosa or stool from human patients. Assessment of intestinal barrier requires measurements beyond the epithelial layer. 'Stress' disorders such as endurance exercise, non-steroidal anti-inflammatory drugs administration, pregnancy and surfactants (such as bile acids and dietary factors such as emulsifiers) increase permeability. Dietary factors can reverse intestinal leakiness and mucosal damage in the 'stress' disorders. Whereas inflammatory or ulcerating intestinal diseases result in leaky gut, no such disease can be cured by simply normalising intestinal barrier function. It is still unproven that restoring barrier function can ameliorate clinical manifestations in GI or systemic diseases. Clinicians should be aware of the potential of barrier dysfunction in GI diseases and of the barrier as a target for future therapy.
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Affiliation(s)
- Michael Camilleri
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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19
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Kastl AJ, Terry NA, Wu GD, Albenberg LG. The Structure and Function of the Human Small Intestinal Microbiota: Current Understanding and Future Directions. Cell Mol Gastroenterol Hepatol 2019; 9:33-45. [PMID: 31344510 PMCID: PMC6881639 DOI: 10.1016/j.jcmgh.2019.07.006] [Citation(s) in RCA: 200] [Impact Index Per Article: 33.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Revised: 07/17/2019] [Accepted: 07/17/2019] [Indexed: 02/07/2023]
Abstract
Despite growing literature characterizing the fecal microbiome and its association with health and disease, few studies have analyzed the microbiome of the small intestine. Here, we examine what is known about the human small intestinal microbiota in terms of community structure and functional properties. We examine temporal dynamics of select bacterial populations in the small intestine, and the effects of dietary carbohydrates and fats on shaping these populations. We then evaluate dysbiosis in the small intestine in several human disease models, including small intestinal bacterial overgrowth, short-bowel syndrome, pouchitis, environmental enteric dysfunction, and irritable bowel syndrome. What is clear is that the bacterial biology, and mechanisms of bacteria-induced pathophysiology, are enormously broad and elegant in the small intestine. Studying the small intestinal microbiota is challenged by rapidly fluctuating environmental conditions in these intestinal segments, as well as the complexity of sample collection and bioinformatic analysis. Because the functionality of the digestive tract is determined primarily by the small intestine, efforts must be made to better characterize this unique and important microbial ecosystem.
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Affiliation(s)
- Arthur J. Kastl
- Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania,Correspondence Address correspondence to: Arthur J. Kastl Jr, MD, Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, 3401 Civic Center Boulevard, 7NW, Philadelphia, Pennsylvania 19104. fax: (215) 590-3606.
| | - Natalie A. Terry
- Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Gary D Wu
- Division of Gastroenterology, Hepatology, and Nutrition, The University of Pennsylvania, Philadelphia, Pennsylvania
| | - Lindsey G. Albenberg
- Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
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20
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Lauro A, Lacaille F. Short bowel syndrome in children and adults: from rehabilitation to transplantation. Expert Rev Gastroenterol Hepatol 2019; 13:55-70. [PMID: 30791840 DOI: 10.1080/17474124.2019.1541736] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Short bowel syndrome (SBS) is a dramatic clinical condition in both children and adults; the residual bowel length is not sufficient to avoid intestinal failure, with subsequent malnutrition and growth retardation, and intravenous support is required to provide the nutrients normally coming from the intestine. Apart from the primary disease, the medical status can be worsened by complications of intestinal failure: if there are irreversible, the prognosis is poor unless a successful intestinal rehabilitation is achieved. Areas covered: The rescue of the remnant small bowel requires a multidisciplinary expertise to achieve digestive autonomy. The use of intestinal trophic factors has shown encouraging results in improving the intestinal adaptation process. Whenever the residual bowel length is inadequate, in a well-selected population weaning parenteral nutrition (PN) off could be attempted by surgery through lengthening procedures. A further subset of patients, with total and irreversible intestinal failure and severe complications on PN, may have an indication to intestinal transplantation. This procedure is still affected by poor long-term results. Expert commentary: Novel approaches developed through a multidisciplinary team work, such as manipulation of microbiota or tissue bioengineering, should be added to current therapies to treat successfully SBS.
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Affiliation(s)
- Augusto Lauro
- a Emergency Surgery Department , St. Orsola University Hospital , Bologna , Italy
| | - Florence Lacaille
- b Gastroenterology Hepatology Nutrition Unit , Hôpital Necker-Enfants Malades , Paris , France
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21
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George F, Daniel C, Thomas M, Singer E, Guilbaud A, Tessier FJ, Revol-Junelles AM, Borges F, Foligné B. Occurrence and Dynamism of Lactic Acid Bacteria in Distinct Ecological Niches: A Multifaceted Functional Health Perspective. Front Microbiol 2018; 9:2899. [PMID: 30538693 PMCID: PMC6277688 DOI: 10.3389/fmicb.2018.02899] [Citation(s) in RCA: 93] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Accepted: 11/12/2018] [Indexed: 12/15/2022] Open
Abstract
Lactic acid bacteria (LAB) are representative members of multiple ecosystems on earth, displaying dynamic interactions within animal and plant kingdoms in respect with other microbes. This highly heterogeneous phylogenetic group has coevolved with plants, invertebrates, and vertebrates, establishing either mutualism, symbiosis, commensalism, or even parasitism-like behavior with their hosts. Depending on their location and environment conditions, LAB can be dominant or sometimes in minority within ecosystems. Whatever their origins and relative abundance in specific anatomic sites, LAB exhibit multifaceted ecological and functional properties. While some resident LAB permanently inhabit distinct animal mucosal cavities, others are provided by food and may transiently occupy the gastrointestinal tract. It is admitted that the overall gut microbiome has a deep impact on health and diseases. Here, we examined the presence and the physiological role of LAB in the healthy human and several animal microbiome. Moreover, we also highlighted some dysbiotic states and related consequences for health, considering both the resident and the so-called "transionts" microorganisms. Whether LAB-related health effects act collectively or follow a strain-specificity dogma is also addressed. Besides the highly suggested contribution of LAB to interplay with immune, metabolic, and even brain-axis regulation, the possible involvement of LAB in xenobiotic detoxification processes and metal equilibrium is also tackled. Recent technological developments such as functional metagenomics, metabolomics, high-content screening and design in vitro and in vivo experimental models now open new horizons for LAB as markers applied for disease diagnosis, susceptibility, and follow-up. Moreover, identification of general and more specific molecular mechanisms based on antioxidant, antimicrobial, anti-inflammatory, and detoxifying properties of LAB currently extends their selection and promising use, either as probiotics, in traditional and functional foods, for dedicated treatments and mostly for maintenance of normobiosis and homeostasis.
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Affiliation(s)
- Fanny George
- Université de Lille, Inserm, CHU Lille, U995 – LIRIC – Lille Inflammation Research International Center, Lille, France
| | - Catherine Daniel
- Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 8204 – CIIL – Center for Infection and Immunity of Lille, Lille, France
| | - Muriel Thomas
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France
| | - Elisabeth Singer
- Université de Lille, Inserm, CHU Lille, U995 – LIRIC – Lille Inflammation Research International Center, Lille, France
| | - Axel Guilbaud
- Université de Lille, Inserm, CHU Lille, U995 – LIRIC – Lille Inflammation Research International Center, Lille, France
| | - Frédéric J. Tessier
- Université de Lille, Inserm, CHU Lille, U995 – LIRIC – Lille Inflammation Research International Center, Lille, France
| | - Anne-Marie Revol-Junelles
- Laboratoire d’Ingénierie des Biomolécules, École Nationale Supérieure d’Agronomie et des Industries Alimentaires – Université de Lorraine, Vandœuvre-lès-Nancy, France
| | - Frédéric Borges
- Laboratoire d’Ingénierie des Biomolécules, École Nationale Supérieure d’Agronomie et des Industries Alimentaires – Université de Lorraine, Vandœuvre-lès-Nancy, France
| | - Benoît Foligné
- Université de Lille, Inserm, CHU Lille, U995 – LIRIC – Lille Inflammation Research International Center, Lille, France
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22
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Abstract
PURPOSE OF REVIEW Short bowel syndrome (SBS) is a rare disease but with many complications due to intestinal failure, parenteral nutrition and underlying disease. A better prevention, comprehension and treatment could improve the outcome of these patients. RECENT FINDINGS Recent studies have been published on acute intestinal failure, first cause of SBS, and gives us strategy to avoid extended intestinal resection and thus SBS. There has been progress in the comprehension of intestinal adaptation, characterized by improvements in intestinal absorption, changes on hormonal secretion, development of a hyperphagia and dysbiosis of the gut microbiota. Hormonal treatment focusing on intestinal rehabilitation by promoting intestinal hyperadaptation has been proposed in patients with SBS, who require parenteral nutrition and intravenous fluids, such as glucagon-like peptide-2 (GLP-2) analog which is now recommended by the latest European Society for Clinical Nutrition and Metabolism Guidelines. SUMMARY Multimodal treatment of acute meseteric ischemia may avoid intestinal resection and is an effective prevention strategy for SBS. New understandings in intestinal adaptation can help us to optimize this adaptation, including with hormonal therapy. GLP-2 analog is now the treatment of reference in SBS patients with chronic intestinal failure.
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Affiliation(s)
- Lore Billiauws
- Department of Gastroenterology and Nutrition Support, APHP Beaujon Hospital
- Gastrointestinal and Metabolic Dysfunctions in Nutritional Pathologies, Inserm UMR 1149, Centre de Recherche sur l'Inflammation Paris Montmartre, UFR de Médecine Paris Diderot, Paris, France
| | - Olivier Corcos
- Department of Gastroenterology and Nutrition Support, APHP Beaujon Hospital
| | - Francisca Joly
- Department of Gastroenterology and Nutrition Support, APHP Beaujon Hospital
- Gastrointestinal and Metabolic Dysfunctions in Nutritional Pathologies, Inserm UMR 1149, Centre de Recherche sur l'Inflammation Paris Montmartre, UFR de Médecine Paris Diderot, Paris, France
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23
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Abstract
Short bowel syndrome with intestinal failure is a rare disease with a massive impairment in quality of life, requiring a multidisciplinary team approach to medical, surgical, and nutritional therapy. Current pharmacological and surgical therapeutic options are limited; an important cornerstone is enteral and parenteral nutrition. The changed physiology of carbohydrate digestion plays a major role in the adaptation process and can be a target for specific enteral nutrition interventions. An important prognostic factor is the preservation of at least portions of the colon in continuity with small bowel. This strategy has to include an evaluation of the anatomical situation and small bowel absorptive capacity, adaptation processes, and luminal microbiota including its fermentative properties. Starch is probably the most important complex carbohydrate in short bowel syndrome nutrition, because it is absorbed or fermented almost completely. Benefits of supplementation with complex carbohydrates include improved adaptive processes, positive trophic effects on the mucosa and its hormonal response, longer transit time, and possibly a faster time to wean from parenteral nutrition, but supplementation advice needs to weigh carefully the risks and benefits, especially considering bacterial overgrowth, osmotic load, and D-lactate acidosis.
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Parenteral Nutrition-Associated Liver Disease: The Role of the Gut Microbiota. Nutrients 2017; 9:nu9090987. [PMID: 28880224 PMCID: PMC5622747 DOI: 10.3390/nu9090987] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Revised: 08/28/2017] [Accepted: 08/30/2017] [Indexed: 02/07/2023] Open
Abstract
Parenteral nutrition (PN) provides life-saving nutritional support in situations where caloric supply via the enteral route cannot cover the necessary needs of the organism. However, it does have serious adverse effects, including parenteral nutrition-associated liver disease (PNALD). The development of liver injury associated with PN is multifactorial, including non-specific intestine inflammation, compromised intestinal permeability, and barrier function associated with increased bacterial translocation, primary and secondary cholangitis, cholelithiasis, short bowel syndrome, disturbance of hepatobiliary circulation, lack of enteral nutrition, shortage of some nutrients (proteins, essential fatty acids, choline, glycine, taurine, carnitine, etc.), and toxicity of components within the nutrition mixture itself (glucose, phytosterols, manganese, aluminium, etc.). Recently, an increasing number of studies have provided evidence that some of these factors are directly or indirectly associated with microbial dysbiosis in the intestine. In this review, we focus on PN-induced changes in the taxonomic and functional composition of the microbiome. We also discuss immune cell and microbial crosstalk during parenteral nutrition, and the implications for the onset and progression of PNALD. Finally, we provide an overview of recent advances in the therapeutic utilisation of pro- and prebiotics for the mitigation of PN-associated liver complications.
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25
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Celiker H. A new proposed mechanism of action for gastric bypass surgery: Air hypothesis. Med Hypotheses 2017; 107:81-89. [PMID: 28915970 DOI: 10.1016/j.mehy.2017.08.012] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 07/02/2017] [Accepted: 08/08/2017] [Indexed: 02/07/2023]
Abstract
Roux-en-Y gastric bypass (RYGB) surgery is one of the most effective treatments for obesity and type II diabetes. RYGB was originally believed to work by mechanically restricting caloric intake or causing macronutrient malabsorption. However, such mechanical effects play no role in the remarkable efficacy of gastric bypass. Instead, mounting evidence shows that altered neuroendocrine signaling is responsible for the weight reducing effects of RYGB. The exact mechanism of this surgical response is still a mystery. Here, we propose that RYGB leads to weight loss primarily by inducing a functional shift in the gut microbiome, manifested by a relative expansion of aerobic bacteria numbers in the colon. We point to compelling evidence that gastric bypass changes the function of the microbiome by disrupting intestinal gas homeostasis, causing excessive transit of swallowed air (oxygen) into the colon.
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Affiliation(s)
- Hasan Celiker
- Xeno Biosciences Inc., 12 Mt Auburn St #7, Cambridge, MA, USA.
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26
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Aladegbami B, Barron L, Bao J, Colasanti J, Erwin CR, Warner BW, Guo J. Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine. Sci Rep 2017; 7:5580. [PMID: 28717211 PMCID: PMC5514129 DOI: 10.1038/s41598-017-06070-w] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Accepted: 06/07/2017] [Indexed: 12/13/2022] Open
Abstract
Intestinal tuft cells are one of 4 secretory cell linages in the small intestine and the source of IL-25, a critical initiator of the type 2 immune response to parasite infection. When Raptor, a critical scaffold protein for mammalian target of rapamycin complex 1 (mTORC1), was acutely deleted in intestinal epithelium via Tamoxifen injection in Tritrichomonas muris (Tm) infected mice, tuft cells, IL-25 in epithelium and IL-13 in the mesenchyme were significantly reduced, but Tm burden was not affected. When Tm infected mice were treated with rapamycin, DCLK1 and IL-25 expression in enterocytes and IL-13 expression in mesenchyme were diminished. After massive small bowel resection, tuft cells and Tm were diminished due to the diet used postoperatively. The elimination of Tm and subsequent re-infection of mice with Tm led to type 2 immune response only in WT, but Tm colonization in both WT and Raptor deficient mice. When intestinal organoids were stimulated with IL-4, tuft cells and IL-25 were induced in both WT and Raptor deficient organoids. In summary, our study reveals that enterocyte specific Raptor is required for initiating a type 2 immune response which appears to function through the regulation of mTORC1 activity.
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Affiliation(s)
- Bola Aladegbami
- Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USA
| | - Lauren Barron
- Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USA
| | - James Bao
- Department of Biology, Washington University in St. Louis, St. Louis, MO, 63110, USA
| | - Jason Colasanti
- Fischell Department of Bioengineering in the A. James Clark School of Engineering at the University of Maryland, College Park, MD, 20742, USA
| | - Christopher R Erwin
- Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USA
| | - Brad W Warner
- Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USA
| | - Jun Guo
- Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USA.
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27
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Gillard L, Mayeur C, Robert V, Pingenot I, Le Beyec J, Bado A, Lepage P, Thomas M, Joly F. Microbiota Is Involved in Post-resection Adaptation in Humans with Short Bowel Syndrome. Front Physiol 2017; 8:224. [PMID: 28469580 PMCID: PMC5395573 DOI: 10.3389/fphys.2017.00224] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2016] [Accepted: 03/28/2017] [Indexed: 12/19/2022] Open
Abstract
Short bowel syndrome (SBS) is characterized by severe intestinal malabsorption following restrictive surgery. The objective of this study was to determine the functional contribution of SBS-microbiota after resection. It is well-known that SBS-microbiota displayed specific features with a prevalence of Lactobacillus, a low amount of some anaerobic microbes (Clostridium leptum) and an accumulation of fecal lactate in some patients. Patients with jejuno-colonic anastomosis were stratified according to the presence of lactate in their feces and, we observe that the lactate-producing bacteria were predominant in the sub-group of patients accumulating fecal lactate. One case of D-encephalopathy crisis occurred when the D-lactate isoform accumulated in the feces and plasma bicarbonate levels decreased. The fecal sample at the time of the encephalopathy was transferred to germ free rats (SBS-H rats). The SBS-H microbiota conserved some characteristics of the SBS donnor, predominated by lactate-producing bacteria (mainly Lactobacillus), a low level of lactate-consuming bacteria and undetectable C. leptum. However, lactate did not accumulate in feces of recipient rats and the D-encephalopathy was not reproduced in SBS-H rats. This suggests that the intact small bowel of the recipient rats protected them from lactate accumulation and that D-lactate encephalopathy can occur only in the absence of small intestine. After fecal transfer, we also show that gnotobiotic rats exhibited high levels of circulating GLP-1 and ghrelin, two hormones that are known to be induced in SBS patients. Therefore, the microbiota of SBS is a reservoir of biological signals involved in post-resection adaptation.
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Affiliation(s)
- Laura Gillard
- Institut National de la Santé et de la Recherche Médicale UMR 1149, L'Unité de Formation de Recherche de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, Assistance Publique - Hôpitaux de Paris, Départements Hospitalo Universitaires UnityParis, France
| | - Camille Mayeur
- Micalis Institute, Institut National de la Recherche Agronomique, AgroParisTech, Université Paris-SaclayJouy-en-Josas, France
| | - Véronique Robert
- Micalis Institute, Institut National de la Recherche Agronomique, AgroParisTech, Université Paris-SaclayJouy-en-Josas, France
| | - Isabelle Pingenot
- Service de Gastroenterologie et Assistance Nutritive, Hôpital BeaujonClichy, France
| | - Johanne Le Beyec
- Institut National de la Santé et de la Recherche Médicale UMR 1149, L'Unité de Formation de Recherche de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, Assistance Publique - Hôpitaux de Paris, Départements Hospitalo Universitaires UnityParis, France.,Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière-Charles Foix, Biochimie Endocrinienne et OncologiqueParis, France.,Université Pierre et Marie Curie, Sorbonne UniversitéParis, France
| | - André Bado
- Institut National de la Santé et de la Recherche Médicale UMR 1149, L'Unité de Formation de Recherche de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, Assistance Publique - Hôpitaux de Paris, Départements Hospitalo Universitaires UnityParis, France
| | - Patricia Lepage
- Micalis Institute, Institut National de la Recherche Agronomique, AgroParisTech, Université Paris-SaclayJouy-en-Josas, France
| | - Muriel Thomas
- Micalis Institute, Institut National de la Recherche Agronomique, AgroParisTech, Université Paris-SaclayJouy-en-Josas, France
| | - Francisca Joly
- Institut National de la Santé et de la Recherche Médicale UMR 1149, L'Unité de Formation de Recherche de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, Assistance Publique - Hôpitaux de Paris, Départements Hospitalo Universitaires UnityParis, France.,Service de Gastroenterologie et Assistance Nutritive, Hôpital BeaujonClichy, France
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28
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Billiauws L, Bataille J, Boehm V, Corcos O, Joly F. Teduglutide for treatment of adult patients with short bowel syndrome. Expert Opin Biol Ther 2017; 17:623-632. [DOI: 10.1080/14712598.2017.1304912] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Lore Billiauws
- Hopital Beaujon - Department of Gastroenterology and Nutrition Support, APHP - University Paris VII, Clichy, France
| | - Julie Bataille
- Hopital Beaujon - Department of Pharmacy, APHP - University Paris VII, Clichy, France
| | - Vanessa Boehm
- Hopital Beaujon - Department of Gastroenterology and Nutrition Support, APHP - University Paris VII, Clichy, France
| | - Olivier Corcos
- Hopital Beaujon - Department of Gastroenterology and Nutrition Support, APHP - University Paris VII, Clichy, France
- Laboratory for Vascular Translational Science, UFR de Médecine Paris Diderot, Paris, France
| | - Francisca Joly
- Hopital Beaujon - Department of Gastroenterology and Nutrition Support, APHP - University Paris VII, Clichy, France
- Centre de Recherche sur l’Inflammation, Gastrointestinal and Metabolic Dysfunctions in Nutritional Pathologies, Paris, France
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29
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Gillard L, Billiauws L, Stan-Iuga B, Ribeiro-Parenti L, Jarry AC, Cavin JB, Cluzeaud F, Mayeur C, Thomas M, Freund JN, Lacorte JM, Le Gall M, Bado A, Joly F, Le Beyec J. Enhanced Ghrelin Levels and Hypothalamic Orexigenic AgRP and NPY Neuropeptide Expression in Models of Jejuno-Colonic Short Bowel Syndrome. Sci Rep 2016; 6:28345. [PMID: 27323884 PMCID: PMC4914859 DOI: 10.1038/srep28345] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 06/01/2016] [Indexed: 12/20/2022] Open
Abstract
Short bowel syndrome (SBS) patients developing hyperphagia have a better outcome. Gastrointestinal endocrine adaptations help to improve intestinal functions and food behaviour. We investigated neuroendocrine adaptations in SBS patients and rat models with jejuno-ileal (IR-JI) or jejuno-colonic (IR-JC) anastomosis with and without parenteral nutrition. Circulating levels of ghrelin, PYY, GLP-1, and GLP-2 were determined in SBS rat models and patients. Levels of mRNA for proglucagon, PYY and for hypothalamic neuropeptides were quantified by qRT-PCR in SBS rat models. Histology and immunostaining for Ki67, GLP-1 and PYY were performed in SBS rats. IR-JC rats, but not IR-JI, exhibited significantly higher crypt depths and number of Ki67-positive cells than sham. Fasting and/or postprandial plasma ghrelin and PYY concentrations were higher, or tend to be higher, in IR-JC rats and SBS-JC patients than in controls. Proglucagon and Pyy mRNA levels were significantly enhanced in IR-JC rats. Levels of mRNA coding hypothalamic orexigenic NPY and AgRP peptides were significantly higher in IR-JC than in sham rats. We demonstrate an increase of plasma ghrelin concentrations, major changes in hypothalamic neuropeptides levels and greater induction of PYY in SBS-JC rats and patients suggesting that jejuno-colonic continuity creates a peculiar environment promoting further gut-brain adaptations.
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Affiliation(s)
- Laura Gillard
- Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France
| | - Lore Billiauws
- Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France
- AP-HP, Hôpital Beaujon, Service de Gastroentérologie et d’Assistance nutritive, Clichy, France
| | - Bogdan Stan-Iuga
- Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France
| | - Lara Ribeiro-Parenti
- Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France
- AP-HP, Hôpital Bichat - Claude Bernard, Service de Chirurgie Générale et Digestive, F-75018 Paris, France
| | - Anne-Charlotte Jarry
- Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France
| | - Jean-Baptiste Cavin
- Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France
| | - Françoise Cluzeaud
- Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France
| | - Camille Mayeur
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France
| | - Muriel Thomas
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France
| | - Jean-Noël Freund
- INSERM UMR_S1113, Université de Strasbourg, Faculté de Médecine, FMTS, 67081 Strasbourg, France
| | - Jean-Marc Lacorte
- INSERM, UMR_S 1166, Research Institute of Cardiovascular Disease, Metabolism and Nutrition, ICAN, Université Pierre et Marie Curie, Sorbonne Université, F-75013, Paris, France
- AP-HP, Hôpital Pitié-Salpêtrière-Charles Foix, Biochimie Endocrinienne et Oncologique, F-75651, Paris, Cedex
- Université Pierre et Marie Curie, Sorbonne Université, F-75005, Paris, France
| | - Maude Le Gall
- Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France
| | - André Bado
- Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France
| | - Francisca Joly
- Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France
- AP-HP, Hôpital Beaujon, Service de Gastroentérologie et d’Assistance nutritive, Clichy, France
| | - Johanne Le Beyec
- Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France
- AP-HP, Hôpital Pitié-Salpêtrière-Charles Foix, Biochimie Endocrinienne et Oncologique, F-75651, Paris, Cedex
- Université Pierre et Marie Curie, Sorbonne Université, F-75005, Paris, France
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