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Ávila-Arres IE, Reis De Souza TC, Ramírez-Rodríguez E, Mariscal-Landín G. Determination of Plasma Metabolites and Basal Ileal Endogenous Amino Acid Losses in Growing Pigs Fed a Nitrogen-Free or Casein Diet. J Anim Physiol Anim Nutr (Berl) 2025; 109:487-494. [PMID: 39511875 DOI: 10.1111/jpn.14067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 09/17/2024] [Accepted: 10/24/2024] [Indexed: 11/15/2024]
Abstract
The nitrogen-free diet (NFD) method for determining basal ileal endogenous losses (BEL) of amino acids (AA) has been associated with different metabolic abnormalities that can affect the accurate determination of BEL. Consequently, the use of highly digestible proteins has been suggested. This study aimed to determine the metabolic status and BEL of AA in pigs fed either an NFD or a casein (CAS) diet. Eight cannulated, castrated male pigs (39.8 kg) were randomly assigned to a 2 × 2 crossover design. An NFD diet based on corn starch, dextrose, cellulose, oil, vitamins and minerals was used. The CAS diet was equivalent, but 18% of the corn starch was replaced with casein. Pigs were fed one of the diets for a 7-day period, and blood samples were collected at the beginning and end of each period to determine plasma metabolites. Ileal digesta samples were collected on Days 6 and 7 to estimate the BEL of the AA. Results indicated that plasma albumin was significantly higher (p < 0.05) in pigs fed the CAS diet, whereas creatinine and LDL levels were higher (p < 0.03) in pigs fed the NFD. No significant differences were observed in the levels of other plasma metabolites. The BEL of protein did not differ between diets. However, in pigs fed the CAS diet, the BEL of glutamic acid, aspartic acid, serine, glycine, histidine, threonine, alanine, tyrosine and valine significantly increased (p < 0.05), while isoleucine showed a tendency to increase (p = 0.06). In conclusion, NFD did not significantly affect energy and lipid metabolism in pigs. However, the decrease in albumin synthesis and increase in plasma creatinine levels indicate that pigs fed NFD have a negative protein balance, affecting the estimation of the BEL of AA. Therefore, it is essential to consider the metabolic state of animals when estimating the BEL of AA.
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Affiliation(s)
- Iris Elisa Ávila-Arres
- Posgrado en Ciencias de la Producción y de la Salud Animal, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Cuautitlan Izcalli, Mexico
| | | | - Ericka Ramírez-Rodríguez
- Centro Nacional de Investigación Disciplinaria en Fisiología y Mejoramiento Animal, INIFAP, Queretaro, Mexico
| | - Gerardo Mariscal-Landín
- Centro Nacional de Investigación Disciplinaria en Fisiología y Mejoramiento Animal, INIFAP, Queretaro, Mexico
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Starke S, Harris DMM, Paulay A, Aden K, Waschina S. Comparative analysis of amino acid auxotrophies and peptidase profiles in non-dysbiotic and dysbiotic small intestinal microbiomes. Comput Struct Biotechnol J 2025; 27:821-831. [PMID: 40103612 PMCID: PMC11914904 DOI: 10.1016/j.csbj.2025.02.004] [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: 11/12/2024] [Revised: 02/10/2025] [Accepted: 02/10/2025] [Indexed: 03/20/2025] Open
Abstract
Small Intestinal Bacterial Overgrowth (SIBO) is linked to various diseases and has been associated with altered serum amino acid levels. However, the direct role of the gut microbiome in these changes remains unconfirmed. This study employs genome-scale metabolic modeling to predict amino acid auxotrophy and peptidase gene profiles in the small intestinal microbiomes of SIBO and non-SIBO subjects. Auxotrophy and peptidase gene profiles were further examined in the large intestinal microbiome under non-dysbiotic conditions to assess their similarity to the microbial SIBO profile. Our analysis revealed that the abundance of auxotrophic bacteria is higher in the microbiota of the small intestine than in the large intestine in non-dysbiotic controls. In patients with SIBO, the abundance of auxotrophies in the small intestine decreased compared to non-SIBO subjects. Peptidase gene profiles in non-dysbiotic individuals were distinct between small and large intestinal microbiomes, with fewer extracellular peptidase genes in small intestine microbiomes. In SIBO, extracellular peptidase genes increased compared to non-SIBO subjects. Further, there were more significant associations between the abundance of auxotrophies and peptidase genes in microbiomes of the small intestine compared to the large intestine. In conclusion, the auxotrophy and peptidase gene profiles of the small and large intestinal microbiomes were distinct. In SIBO, the small intestinal microbiome shifts towards a metabolic state resembling that of the large intestine, particularly in its increased abundance of extracellular peptidase genes. This highlights the potential of genome-scale metabolic modeling in identifying metabolic disruptions associated with SIBO, which could inform the development of targeted interventions.
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Affiliation(s)
- Svenja Starke
- Institute of Human Nutrition and Food Science, Department of Nutriinformatics, Kiel University, Kiel, 24118, Germany
| | - Danielle M M Harris
- Institute of Human Nutrition and Food Science, Department of Nutriinformatics, Kiel University, Kiel, 24118, Germany
- Institute of Clinical Molecular Biology, Kiel University, Rosalind-Franklin-Straße 12, Kiel, 24118, Germany
- Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, 24105, Germany
| | - Amandine Paulay
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas 78350, France
- Université Paris-Saclay, INRAE, MaIAGE, Jouy-en-Josas 78350, France
- Biomathematica, Ajaccio 20000, France
| | - Konrad Aden
- Institute of Clinical Molecular Biology, Kiel University, Rosalind-Franklin-Straße 12, Kiel, 24118, Germany
- Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, 24105, Germany
| | - Silvio Waschina
- Institute of Human Nutrition and Food Science, Department of Nutriinformatics, Kiel University, Kiel, 24118, Germany
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Bandyopadhyay S, Kashyap S, Calvez J, Devi S, Azzout-Marniche D, Tomé D, Kurpad AV, Gaudichon C. Evaluation of Protein Quality in Humans and Insights on Stable Isotope Approaches to Measure Digestibility - A Review. Adv Nutr 2022; 13:1131-1143. [PMID: 34755836 PMCID: PMC9340995 DOI: 10.1093/advances/nmab134] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 10/15/2021] [Accepted: 11/05/2021] [Indexed: 11/14/2022] Open
Abstract
The recent Food and Agricultural Organization/World Health Organization/United Nations University expert consultations on protein requirements and quality have emphasized the need for the new Digestible Indispensable Amino Acid Score (DIAAS), as a measure of protein quality. This requires human measurements of the true ileal digestibility of individual indispensable amino acids (IAAs) until the end of the small intestine. Digestibility is measured using standard oro-ileal balance methods, which can only be achieved by an invasive naso-ileal intubation in healthy participants or fistulation at the terminal ileum. Significant efforts have been made over the last 2 decades to develop noninvasive or minimally invasive methods to measure IAA digestibility in humans. The application of intrinsically labeled (with stable isotopes like 13C, 15N, and 2H) dietary proteins has helped in circumventing the invasive oro-ileal balance techniques and allowed the differentiation between endogenous and exogenous protein. The noninvasive indicator amino acid oxidation (IAAO) technique, which is routinely employed to measure IAA requirements, has been modified to estimate metabolic availability (a sum of digestibility and utilization) of IAA in foods, but provides an estimate for a single IAA at a time and is burdensome for participants. The recently developed minimally invasive dual isotope tracer method measures small intestinal digestibility of multiple amino acids at once and is suitable for use in vulnerable groups and disease conditions. However, it remains to be validated against standard oro-ileal balance techniques. This review critically evaluates and compares the currently available stable isotope-based protein quality evaluation methods with a focus on the digestibility and metabolic availability measurements in humans. In view of building a reliable DIAAS database of various protein sources and subsequently supporting protein content claims in food labeling, a re-evaluation and harmonization of the available methods are necessary.
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Affiliation(s)
- Sulagna Bandyopadhyay
- Division of Nutrition, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India
| | - Sindhu Kashyap
- Division of Nutrition, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India
| | - Juliane Calvez
- Université Paris-Saclay, AgroParisTech, INRAE (National Research Institute for Agriculture, Food, and Environment), UMR PNCA (Research Unit for Nutrition Physiology and Dietary Behavior), Paris, France
| | - Sarita Devi
- Division of Nutrition, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India
| | - Dalila Azzout-Marniche
- Université Paris-Saclay, AgroParisTech, INRAE (National Research Institute for Agriculture, Food, and Environment), UMR PNCA (Research Unit for Nutrition Physiology and Dietary Behavior), Paris, France
| | - Daniel Tomé
- Université Paris-Saclay, AgroParisTech, INRAE (National Research Institute for Agriculture, Food, and Environment), UMR PNCA (Research Unit for Nutrition Physiology and Dietary Behavior), Paris, France
| | - Anura V Kurpad
- Division of Nutrition, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India
- Department of Physiology, St. John's Medical College, St. John's National Academy of Health Sciences, Bangalore, India
| | - Claire Gaudichon
- Université Paris-Saclay, AgroParisTech, INRAE (National Research Institute for Agriculture, Food, and Environment), UMR PNCA (Research Unit for Nutrition Physiology and Dietary Behavior), Paris, France
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Kroupina K, Bémeur C, Rose CF. Amino acids, ammonia, and hepatic encephalopathy. Anal Biochem 2022; 649:114696. [PMID: 35500655 DOI: 10.1016/j.ab.2022.114696] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 03/30/2022] [Accepted: 04/21/2022] [Indexed: 11/30/2022]
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The role of dietary proteins and carbohydrates in gut microbiome composition and activity: A review. Food Hydrocoll 2021. [DOI: 10.1016/j.foodhyd.2021.106911] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Fiber digestibility in growing pigs fed common fiber-rich ingredients: a systematic review. ANNALS OF ANIMAL SCIENCE 2021. [DOI: 10.2478/aoas-2021-0050] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Abstract
The application of high-fiber ingredients in the swine feed industry has some limitations considering that high amounts of fiber are resistant to endogenous enzymatic degradation in the pig’s gut. However, there is growing interest in fiber fermentation in the intestine of pigs due to their functional properties and potential health benefits. Many strategies have been applied in feed formulations to improve utilization efficiency of fiber-rich ingredients and stimulate their prebiotic effects in pigs. This manuscript reviews chemical compositions, physical properties, and digestibility of fiber-rich diets formulated with fibrous ingredients for growing pigs. Evidences presented in this review indicate there is a great variation in chemical compositions and physical properties of fibrous ingredients, resulting in the discrepancy of energy and fiber digestibility in pig intestine. In practice, fermentation capacity of fiber components in the pig’s intestine can be improved using strategies, such as biological enzymes supplementation and feed processing technologies. Soluble dietary fiber (SDF) and insoluble dietary fiber (IDF), rather than neutral detergent fiber (NDF) and acid detergent fiber (ADF), are recommended in application of pig production to achieve precise feeding. Limitations of current scientific research on determining fiber digestibility and short chain fatty acids (SCFA) production are discussed. Endogenous losses of fiber components from non-dietary materials that result in underestimation of fiber digestibility and SCFA production are discussed in this review. Overall, the purpose of our review is to provide a reference for feeding the pig by choosing the diets formulated with different high-fiber ingredients.
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Chleilat F, Schick A, Deleemans JM, Ma K, Alukic E, Wong J, Noye Tuplin EW, Nettleton JE, Reimer RA. Paternal high protein diet modulates body composition, insulin sensitivity, epigenetics, and gut microbiota intergenerationally in rats. FASEB J 2021; 35:e21847. [PMID: 34405464 DOI: 10.1096/fj.202100198rr] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 07/22/2021] [Accepted: 07/23/2021] [Indexed: 12/19/2022]
Abstract
Mounting evidence demonstrates that paternal diet programs offspring metabolism. However, the contribution of a pre-conception paternal high protein (HP) diet to offspring metabolism, gut microbiota, and epigenetic changes remains unclear. Here we show that paternal HP intake in Sprague Dawley rats programs protective metabolic outcomes in offspring. Compared to paternal high fat/sucrose (HF/S), HP diet improved body composition and insulin sensitivity and improved circulating satiety hormones and cecal short-chain fatty acids compared to HF/S and control diet (P < .05). Further, using 16S rRNA gene sequencing to assess gut microbial composition, we observed increased alpha diversity, distinct bacterial clustering, and increased abundance of Bifidobacterium, Akkermansia, Bacteroides, and Marvinbryantia in HP fathers and/or male and female adult offspring. At the epigenetic level, DNMT1and 3b expression was altered intergenerationally. Our study identifies paternal HP diet as a modulator of gut microbial composition, epigenetic markers, and metabolic function intergenerationally.
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Affiliation(s)
- Faye Chleilat
- Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada
| | - Alana Schick
- International Microbiome Centre, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Julie M Deleemans
- Division of Medical Science and Psychosocial Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Kyle Ma
- Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada
| | - Erna Alukic
- Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada
| | - Jolene Wong
- Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada
| | | | - Jodi E Nettleton
- Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada
| | - Raylene A Reimer
- Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada.,Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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Dave LA, Hayes M, Mora L, Rutherfurd SM, Montoya CA, Moughan PJ. Bioactive Peptides Originating from Gastrointestinal Endogenous Proteins in the Growing Pig: In Vivo Identification. Curr Pharm Des 2021; 27:1382-1395. [PMID: 33292114 DOI: 10.2174/1381612826666201207111209] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 08/17/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Recent in silico and in vitro studies have shown that gastrointestinal endogenous proteins (GEP) are a source of bioactive peptides. To date, however, the presence of such peptides in the lumen of the digestive tract has not been demonstrated. OBJECTIVE We investigated the generation of GEP-derived bioactive peptides in the growing pig fed a proteinfree diet. METHODS Stomach chyme (SC) and jejunal digesta (JD) fractions from 6 growing pigs (two sampling times) were assessed for their angiotensin-I-converting enzyme (ACE-I; EC 3.4.15.1) inhibition, and antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition, ferric reducing antioxidant power (FRAP) and microsomal lipid peroxidation (MLP) inhibition assays. RESULTS Two of the fractions prepared from JD samples inhibited ACE-I and DPPH by 81 (± 2.80)% and 94 (±0.66)%. SC fractions were found to inhibit MLP between 15-39 (±3.52-1.40)%. The study identified over 180 novel peptide sequences that were related to the determined bioactivities, including a porcine serum albuminderived peptide (FAKTCVADESAENCDKS), corresponding to f(7-23) of the human serum albumin peptide LVNEVTEFAKTCVADESAENCDKSLHTLF that was previously identified from the digests of the latter GEP. CONCLUSION This study provides the first in vivo evidence for GEP as a source of bioactive peptides. These new findings help advance our knowledge of the latent bioactive role of GEP-derived peptides in mammalian nutrition and health and their potential pharmaceutical applications.
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Affiliation(s)
- Lakshmi A Dave
- Riddet Institute, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand
| | - Maria Hayes
- Teagasc, The Irish Agricultural and Food Development Authority, Food BioSciences Department, Ashtown, Dublin 15, Ireland
| | - Leticia Mora
- Instituto de Agroquıimica y Tecnologıia de Alimentos (CSIC), Avenida Agustín Escardino 7, 46980 Paterna, Valencia, Spain
| | - Shane M Rutherfurd
- Riddet Institute, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand
| | - Carlos A Montoya
- Riddet Institute, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand
| | - Paul J Moughan
- Riddet Institute, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand
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PH van Trijp M, Wilms E, Ríos-Morales M, Masclee AA, Brummer RJ, Witteman BJ, Troost FJ, Hooiveld GJ. Using naso- and oro-intestinal catheters in physiological research for intestinal delivery and sampling in vivo: practical and technical aspects to be considered. Am J Clin Nutr 2021; 114:843-861. [PMID: 34036315 PMCID: PMC8408849 DOI: 10.1093/ajcn/nqab149] [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: 11/06/2020] [Accepted: 04/09/2021] [Indexed: 01/19/2023] Open
Abstract
Intestinal catheters have been used for decades in human nutrition, physiology, pharmacokinetics, and gut microbiome research, facilitating the delivery of compounds directly into the intestinal lumen or the aspiration of intestinal fluids in human subjects. Such research provides insights about (local) dynamic metabolic and other intestinal luminal processes, but working with catheters might pose challenges to biomedical researchers and clinicians. Here, we provide an overview of practical and technical aspects of applying naso- and oro-intestinal catheters for delivery of compounds and sampling luminal fluids from the jejunum, ileum, and colon in vivo. The recent literature was extensively reviewed, and combined with experiences and insights we gained through our own clinical trials. We included 60 studies that involved a total of 720 healthy subjects and 42 patients. Most of the studies investigated multiple intestinal regions (24 studies), followed by studies investigating only the jejunum (21 studies), ileum (13 studies), or colon (2 studies). The ileum and colon used to be relatively inaccessible regions in vivo. Custom-made state-of-the-art catheters are available with numerous options for the design, such as multiple lumina, side holes, and inflatable balloons for catheter progression or isolation of intestinal segments. These allow for multiple controlled sampling and compound delivery options in different intestinal regions. Intestinal catheters were often used for delivery (23 studies), sampling (10 studies), or both (27 studies). Sampling speed decreased with increasing distance from the sampling syringe to the specific intestinal segment (i.e., speed highest in duodenum, lowest in ileum/colon). No serious adverse events were reported in the literature, and a dropout rate of around 10% was found for these types of studies. This review is highly relevant for researchers who are active in various research areas and want to expand their research with the use of intestinal catheters in humans in vivo.
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Affiliation(s)
- Mara PH van Trijp
- Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands
| | - Ellen Wilms
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Melany Ríos-Morales
- Laboratory of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Ad Am Masclee
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Robert Jan Brummer
- Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Ben Jm Witteman
- Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands,Hospital Gelderse Vallei, Department of Gastroenterology and Hepatology, Ede, The Netherlands
| | - Freddy J Troost
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands,Food Innovation and Health, Centre for Healthy Eating and Food Innovation, Maastricht University, Maastricht, The Netherlands
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Calvez J, Benoit S, Piedcoq J, Khodorova N, Azzout-Marniche D, Tomé D, Benamouzig R, Airinei G, Gaudichon C. Very low ileal nitrogen and amino acid digestibility of zein compared to whey protein isolate in healthy volunteers. Am J Clin Nutr 2021; 113:70-82. [PMID: 33021640 DOI: 10.1093/ajcn/nqaa274] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 09/01/2020] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Whey protein and zein are of nutritional interest due to their high leucine content, but little data are available on their amino acid (AA) ileal digestibility. OBJECTIVE This study aimed to determine ileal digestibility of whey protein isolate (WPI) and zein in healthy volunteers by use of the naso-ileal intubation method, which allows continuous collection of postprandial ileal digesta. METHODS Twenty-two healthy volunteers were intubated with a naso-ileal sampling device positioned at the terminal ileum level. They received a single meal of protein-free biscuits and a drink containing zein (n = 8), WPI (n = 7), or no protein (protein free, n = 7). Ileal effluents and plasma samples were collected over a 9-h postprandial period. Total nitrogen and AA contents were quantified in effluents. True ileal digestibility was calculated after correction for endogenous losses evaluated in the protein-free group. RESULTS True ileal nitrogen digestibility of zein was markedly lower than WPI (60.2 ± 4.5% and 91.2 ± 2.6%, respectively, P = 0.0003). True ileal digestibility of AAs ranged from 87.4 ± 2.7% for threonine to 98.4 ± 1.0% for methionine in the WPI group, and from 59.3 ± 5.6% for methionine to 69.0 ± 5.8% for arginine in the zein group. The digestible indispensable AA (IAA) score was 1.03 (histidine) for WPI and close to 0 for zein, owing to its negligible lysine content. Plasma IAA concentration significantly increased after WPI intake (P = 0.0319), whereas no effect of zein on aminoacidemia was observed, including plasma leucine, despite its high leucine content. CONCLUSIONS Our findings provide data on ileal digestibility of WPI and zein AAs in healthy humans and, in contrast to WPI, zein is poorly digestible. This study was registered at clinicaltrials.gov as NCT03279211.
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Affiliation(s)
- Juliane Calvez
- Université Paris-Saclay, AgroParisTech, National Research Institute for Agriculture, Food and Environment (INRAE), Nutrition Physiology and Ingestive Behavior UMR (unité mixte de recherche) (UMR PNCA), Paris, France
| | - Simon Benoit
- Université Paris-Saclay, AgroParisTech, National Research Institute for Agriculture, Food and Environment (INRAE), Nutrition Physiology and Ingestive Behavior UMR (unité mixte de recherche) (UMR PNCA), Paris, France
| | - Julien Piedcoq
- Université Paris-Saclay, AgroParisTech, National Research Institute for Agriculture, Food and Environment (INRAE), Nutrition Physiology and Ingestive Behavior UMR (unité mixte de recherche) (UMR PNCA), Paris, France
| | - Nadezda Khodorova
- Université Paris-Saclay, AgroParisTech, National Research Institute for Agriculture, Food and Environment (INRAE), Nutrition Physiology and Ingestive Behavior UMR (unité mixte de recherche) (UMR PNCA), Paris, France
| | - Dalila Azzout-Marniche
- Université Paris-Saclay, AgroParisTech, National Research Institute for Agriculture, Food and Environment (INRAE), Nutrition Physiology and Ingestive Behavior UMR (unité mixte de recherche) (UMR PNCA), Paris, France
| | - Daniel Tomé
- Université Paris-Saclay, AgroParisTech, National Research Institute for Agriculture, Food and Environment (INRAE), Nutrition Physiology and Ingestive Behavior UMR (unité mixte de recherche) (UMR PNCA), Paris, France
| | - Robert Benamouzig
- Université Paris-Saclay, AgroParisTech, National Research Institute for Agriculture, Food and Environment (INRAE), Nutrition Physiology and Ingestive Behavior UMR (unité mixte de recherche) (UMR PNCA), Paris, France
| | - Gheorghe Airinei
- Université Paris-Saclay, AgroParisTech, National Research Institute for Agriculture, Food and Environment (INRAE), Nutrition Physiology and Ingestive Behavior UMR (unité mixte de recherche) (UMR PNCA), Paris, France
| | - Claire Gaudichon
- Université Paris-Saclay, AgroParisTech, National Research Institute for Agriculture, Food and Environment (INRAE), Nutrition Physiology and Ingestive Behavior UMR (unité mixte de recherche) (UMR PNCA), Paris, France
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Ansia I, Drackley JK. Technical note: Evaluation of 3 methods to determine mucin protein concentration in ileal digesta of young preweaning calves. J Dairy Sci 2020; 103:6250-6257. [PMID: 32331876 DOI: 10.3168/jds.2019-18121] [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: 12/24/2019] [Accepted: 02/02/2020] [Indexed: 11/19/2022]
Abstract
The use of alternative sources of protein to substitute for milk proteins in milk replacers (MR) can increase the synthesis of endogenous proteins and therefore alter ileal or total-tract digestibility calculations. Mucin is the main component of gastrointestinal mucus and represents the greatest contribution to total endogenous protein. Mucin is difficult to isolate and has not been extensively studied in dairy calves. We explored 3 different procedures to analyze and estimate mucin protein (MUP) in ileal digesta of young dairy calves. Ileal digesta samples were collected from nine 30-d-old ileal-cannulated calves that were enrolled in a 3 × 3 replicated Latin square with 5-d periods. The 3 diets were a control whey protein-based MR (WPC), an isonitrogenous MR in which 50% of the protein was from enzyme-treated soybean meal (ESBM), and an N-free MR (NFREE). Mucin protein concentration and flow were analyzed by fractionation of the digesta and ethanol precipitation; this process served as the reference method. Alternative methods to estimate MUP consisted of using commercial enzymatic kits to analyze glucosamine (N-acetylglucosamine, GlcNAc) and galactosamine (N-acetylgalactosamine, GalNAc), 2 amino-sugars that are highly enriched in mucin. Before GlcNAc determination, samples were processed using 3 different procedures: sample clarification (GLCL), clarification plus hydrolysis (GLCH), and hydrolysis alone (GLHL). The MUP was estimated by regression of the GlcNAc and GalNAc values using previously validated equations. According with the bias and agreement analysis, none of the methods yielded MUP values similar to the reference method. However, GLHL showed a strong association with the reference method (ρ = 0.73). It allowed identifying the smaller MUP flows with NFREE compared with the other 2 diets and detecting the greater flow of ESBM than WPC, as observed with the reference method. Using the GlcNAc values from GLHL and the MUP measured with the reference method, we were able to establish a linear relationship between both methods (adjusted R2 = 0.75). We found that the GLHL method enabled detecting differences in MUP ileal flows between diets differing in protein level and source. Inferences about MUP secretions must be done cautiously because many dietary and physiological factors are involved. The adoption of practical techniques to determine MUP can help to increase our knowledge about gastrointestinal tract function and to improve the accuracy of MR digestibility calculations.
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Affiliation(s)
- I Ansia
- Department of Animal Sciences, University of Illinois, Urbana 61801
| | - J K Drackley
- Department of Animal Sciences, University of Illinois, Urbana 61801.
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Levitt MD, Levitt DG. Use Of Quantitative Modelling To Elucidate The Roles Of The Liver, Gut, Kidney, And Muscle In Ammonia Homeostasis And How Lactulose And Rifaximin Alter This Homeostasis. Int J Gen Med 2019; 12:367-380. [PMID: 31686894 PMCID: PMC6798813 DOI: 10.2147/ijgm.s218405] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 09/24/2019] [Indexed: 12/18/2022] Open
Abstract
Humans must eliminate approximately 1M of ammonia per day while maintaining the blood concentration of this potent neurotoxin at a concentration of only about 30 µM. The mechanisms producing such effective ammonia homeostasis are poorly understood by clinicians due to the multiple organs (liver, gut, kidney and muscle) involved in ammonia homeostasis. Based on literature values we present a novel, simplified description of normal and disordered ammonia and the potential mechanisms whereby the drugs used to treat hepatic encephalopathy, lactulose and rifaximin, lower the blood ammonia concentration. Concepts discussed include the following: 1) only about 44 mmol of ammonia/day (4.4% of total production) reaches the peripheral circulation due to the efficient linkage of amino deamination and the urea cycle in hepatic mitochondria; 2) the gut and kidney contribute roughly equally to delivery of this 44 mmol/day to systemic blood; 3) the bulk of gut ammonia production seemingly originates in the small bowel from bacterial deamination of urea by bacteria and mucosal deamination of circulating and ingested glutamine; 4) the apparent production of ammonia in the small bowel markedly exceeds that quantity that enters the portal blood, indicating that ammonia disposal mechanisms in the small bowel play a major role in ammonia homeostasis. With regard to the hyperammonemia of chronic liver disease: 1) shunting of portal blood around the liver, by itself, can account for commonly observed ammonia elevations; 2) severe portal hypertension causes an increased release of ammonia by the kidney; 3) high blood ammonia is associated with an unexplained massive increase in the muscle uptake of ammonia that could play an important role in limiting hyperammonemia; and 4) a major action of lactulose administration may be the enhancement of ammonia uptake by small bowel bacteria, while the mechanism of action of rifaximin is unclear.
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Affiliation(s)
- Michael D Levitt
- Research Service, Veterans Affairs Medical Center, Minneapolis, MN 55417, USA
| | - David G Levitt
- Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN 55455, USA
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Romano C, Corsetti G, Flati V, Pasini E, Picca A, Calvani R, Marzetti E, Dioguardi FS. Influence of Diets with Varying Essential/Nonessential Amino Acid Ratios on Mouse Lifespan. Nutrients 2019; 11:nu11061367. [PMID: 31216646 PMCID: PMC6628056 DOI: 10.3390/nu11061367] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Revised: 05/20/2019] [Accepted: 06/13/2019] [Indexed: 12/13/2022] Open
Abstract
An adequate intake of essential (EAA) and non-essential amino acids (NEAA) is crucial to preserve cell integrity and whole-body metabolism. EAA introduced with diet may be insufficient to meet the organismal needs, especially under increased physiological requirements or in pathological conditions, and may condition lifespan. We therefore examined the effects of iso-caloric and providing the same nitrogenous content diets, any diet containing different stoichiometric blends of EAA/NEAA, on mouse lifespan. Three groups of just-weaned male Balb/C mice were fed exclusively with special diets with varying EAA/NEAA ratios, ranging from 100%/0% to 0%/100%. Three additional groups of mice were fed with different diets, two based on casein as alimentary proteins, one providing the said protein, one reproducing the amino acidic composition of casein, and the third one, the control group, was fed by a standard laboratory diet. Mouse lifespan was inversely correlated with the percentage of NEAA introduced with each diet. Either limiting EAA, or exceeding NEAA, induced rapid and permanent structural modifications on muscle and adipose tissue, independently of caloric intake. These changes significantly affected food and water intake, body weight, and lifespan. Dietary intake of varying EAA/NEAA ratios induced changes in several organs and profoundly influenced murine lifespan. The balanced content of EAA provided by dietary proteins should be considered as the preferable means for “optimal” nutrition and the elevated or unbalanced intake of NEAA provided by food proteins may negatively affect the health and lifespan of mice.
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Affiliation(s)
- Claudia Romano
- Division of Human Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, 25124 Brescia, Italy.
| | - Giovanni Corsetti
- Division of Human Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, 25124 Brescia, Italy.
| | - Vincenzo Flati
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
| | - Evasio Pasini
- Istituti Clinici Scientifici Maugeri - IRCCS Lumezzane - Cardiac Rehabilitation Division, 25065 Lumezzane (Brescia), Italy.
| | - Anna Picca
- Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, 00168 Rome, Italy.
- Institute of Internal Medicine and Geriatrics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
| | - Riccardo Calvani
- Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, 00168 Rome, Italy.
- Institute of Internal Medicine and Geriatrics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
| | - Emanuele Marzetti
- Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, 00168 Rome, Italy.
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Prebiotic Supplementation of In Vitro Fecal Fermentations Inhibits Proteolysis by Gut Bacteria, and Host Diet Shapes Gut Bacterial Metabolism and Response to Intervention. Appl Environ Microbiol 2019; 85:AEM.02749-18. [PMID: 30824442 DOI: 10.1128/aem.02749-18] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 02/13/2019] [Indexed: 12/22/2022] Open
Abstract
Metabolism of protein by gut bacteria is potentially detrimental due to the production of toxic metabolites, such as ammonia, amines, p-cresol, and indole. The consumption of prebiotic carbohydrates results in specific changes in the composition and/or activity of the microbiota that may confer benefits to host well-being and health. Here, we have studied the impact of prebiotics on proteolysis within the gut in vitro Anaerobic stirred batch cultures were inoculated with feces from omnivores (n = 3) and vegetarians (n = 3) and four protein sources (casein, meat, mycoprotein, and soy protein) with and without supplementation by an oligofructose-enriched inulin. Bacterial counts and concentrations of short-chain fatty acids (SCFA), ammonia, phenol, indole, and p-cresol were monitored during fermentation. Addition of the fructan prebiotic Synergy1 increased levels of bifidobacteria (P = 0.000019 and 0.000013 for omnivores and vegetarians, respectively). Branched-chain fatty acids (BCFA) were significantly lower in fermenters with vegetarians' feces (P = 0.004), reduced further by prebiotic treatment. Ammonia production was lower with Synergy1. Bacterial adaptation to different dietary protein sources was observed through different patterns of ammonia production between vegetarians and omnivores. In volunteer samples with high baseline levels of phenol, indole, p-cresol, and skatole, Synergy1 fermentation led to a reduction of these compounds.IMPORTANCE Dietary protein intake is high in Western populations, which could result in potentially harmful metabolites in the gut from proteolysis. In an in vitro fermentation model, the addition of prebiotics reduced the negative consequences of high protein levels. Supplementation with a prebiotic resulted in a reduction of proteolytic metabolites in the model. A difference was seen in protein fermentation between omnivore and vegetarian gut microbiotas: bacteria from vegetarian donors grew more on soy and Quorn than on meat and casein, with reduced ammonia production. Bacteria from vegetarian donors produced less branched-chain fatty acids (BCFA).
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Luo SH, Chu JG, Huang H, Zhao GR, Yao KC. Targeted puncture of left branch of intrahepatic portal vein in transjugular intrahepatic portosystemic shunt to reduce hepatic encephalopathy. World J Gastroenterol 2019; 25:1088-1099. [PMID: 30862997 PMCID: PMC6406189 DOI: 10.3748/wjg.v25.i9.1088] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Revised: 01/24/2019] [Accepted: 01/28/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Transjugular intrahepatic portosystemic shunt (TIPS) is currently used for the treatment of complications of portal hypertension. The incidence of hepatic encephalopathy (HE) remains a problem in TIPS placement. It has been reported that the right branch mainly receives superior mesenteric venous blood while the left branch mainly receives blood from the splenic vein. We hypothesized that targeted puncture of the left portal vein would divert the non-nutritive blood from the splenic vein into the TIPS shunt; therefore, targeted puncture of the left branch of the intrahepatic portal vein during TIPS may reduce the risk of HE.
AIM To evaluate the influence of targeted puncture of left branch of portal vein in TIPS on HE.
METHODS A retrospective analysis of 1244 patients with portal-hypertension-related complications of refractory ascites or variceal bleeding who underwent TIPS from January 2000 to January 2013 was performed. Patients were divided into group A (targeting left branch of portal vein, n = 937) and group B (targeting right branch of portal vein, n = 307). TIPS-related HE and clinical outcomes were analyzed.
RESULTS The symptoms of ascites and variceal bleeding disappeared within a short time. By the endpoint of follow-up, recurrent bleeding and ascites did not differ significantly between groups A and B (P = 0.278, P = 0.561, respectively). Incidence of HE differed significantly between groups A and B at 1 mo (14.94% vs 36.80%, χ2 = 4.839, P = 0.028), 3 mo (12.48% vs 34.20%, χ2 = 5.054, P = 0.025), 6 mo (10.03% vs 32.24%, χ2 = 6.560, P = 0.010), 9 mo (9.17% vs 31.27%, χ2 = 5.357, P = 0.021), and 12 mo (8.21% vs 28.01, χ2 = 3.848, P = 0.051). There were no significant differences between groups A and B at 3 years (6.61% vs 7.16%, χ2 = 1.204, P = 0.272) and 5 years (5.01% vs 6.18%, χ2 = 0.072, P = 0.562). The total survival rate did not differ between groups A and B (χ2 = 0.226, P = 0.634, log-rank test).
CONCLUSION Targeted puncture of the left branch of the intrahepatic portal vein during TIPS may reduce the risk of HE but has no direct influence on prognosis of portal-hypertension-related complications.
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Affiliation(s)
- Shi-Hua Luo
- Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Jian-Guo Chu
- Department of Radiology, Air Force Medical Center of PLA, Beijing 100142, China
| | - He Huang
- Department of Radiology, Air Force Medical Center of PLA, Beijing 100142, China
| | - Guo-Rui Zhao
- Department of Interventional Radiology, Henan Provincial Infectious Disease Hospital, Zhengzhou 450015, Henan Province, China
| | - Ke-Chun Yao
- Department of Ultrasound, Air Force Medical Center of PLA, Beijing 100142, China
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Adaptation of intestinal fermentation over time in the growing pig is influenced by the amount of kiwi fruit consumed. Br J Nutr 2019; 121:601-614. [DOI: 10.1017/s0007114518003574] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
AbstractThe effect of kiwi fruit at two dietary levels on the adaptation of intestinal fermentation over time in the growing pig was studied. A semi-synthetic fibre-free diet and two semi-synthetic diets containing kiwi fruit as a model fibre source (133 or 266 g/kg (DM basis); 28 or 48 g fibre/kg) were formulated and the diets contained titanium dioxide as an indigestible marker. A total of fourteen ileal cannulated pigs (41 kg body weight) were fed the fibre-free diet for 7 d followed by either the low or high kiwi fruit-containing diets (n 7/diet) for a further 44 d. Ileal digesta and faeces were collected at five times throughout the study. Ileal digesta were fermented (in vitro) with a standard pooled human faecal inoculum, while fresh pig faeces were used as inocula to ferment in vitro a standard purified fibre. Observations were normalised for diet DM intake using the marker. The 16S ribosomal RNA gene copy number of ileal and total faecal bacteria were high for the high-kiwi fruit level diet (P<0·05). The ileal bacteria tended to decrease over time (P<0·1), while the faecal bacteria increased (P<0·05), at the same rate for both diets. The amounts of crude protein and insoluble dietary fibre entering the hindgut changed over time similarly for both diets, whereas for starch it changed only for the low kiwi fruit-containing diet (P<0·05). Changes over time were also observed for the predicted hindgut valeric acid production and butyric acid absorption (P<0·05). In conclusion, adaptational changes over time of some characteristics of intestinal fermentation depended on the dietary level of kiwi fruit.
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Starck CS, Wolfe RR, Moughan PJ. Endogenous Amino Acid Losses from the Gastrointestinal Tract of the Adult Human-A Quantitative Model. J Nutr 2018; 148:1871-1881. [PMID: 30247627 DOI: 10.1093/jn/nxy162] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 06/28/2018] [Indexed: 11/12/2022] Open
Abstract
Background The loss of endogenous (nondietary) amino acids (AAs) from the gastrointestinal tract (GIT) is an important component underlying the adult human dietary requirement for protein and essential AAs (EAAs). Although data with regard to endogenous AA losses to the end of the small intestine have been published, to our knowledge there are no direct measures of colonic endogenous AA losses. Objective The objective was to derive quantitative estimates for daily endogenous protein and EAAs lost from the colon of the adult human. Methods A factorial model was developed for the prediction of endogenous AA losses across the adult human GIT. Estimates of AAs entering the upper GIT lumen were combined with relative protein synthesis rates in the colon to predict colonic AA losses. The AA composition of human colonic endogenous protein was calculated by estimating the relative contributions of epithelial cell protein and mucin protein on the basis of published data for cell shedding in the pig small intestine, small intestinal protein synthesis rates in pigs and humans, and human upper and lower GIT surface areas. Colonic AA losses were summed with empirical estimates of ileal AA losses in humans to estimate total daily GIT endogenous AA losses. Results Colonic AA loss was estimated to total 3.5 g/d in the adult male human, comprising 33% of total GIT endogenous AA loss (10.2 g/d). GIT essential AA losses accounted for 25-97% of the current recommended daily AA requirement for adult humans. For threonine, colonic losses were 54% of total GIT threonine losses, which were 97% of the current recommended daily threonine requirement. Conclusions Colonic endogenous AA losses represent a significant fraction of total GIT endogenous AA losses. The requirement of the GIT for EAAs to replace AAs lost via the gut lumen comprises a substantial proportion of the Recommended Daily Intake of AAs.
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Affiliation(s)
- Carlene S Starck
- Riddet Institute, Massey University, Palmerston North, New Zealand
| | - Robert R Wolfe
- Reynolds Institute on Aging and Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR
| | - Paul J Moughan
- Riddet Institute, Massey University, Palmerston North, New Zealand
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18
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Levitt DG, Levitt MD. A model of blood-ammonia homeostasis based on a quantitative analysis of nitrogen metabolism in the multiple organs involved in the production, catabolism, and excretion of ammonia in humans. Clin Exp Gastroenterol 2018; 11:193-215. [PMID: 29872332 PMCID: PMC5973424 DOI: 10.2147/ceg.s160921] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Increased blood ammonia (NH3) is an important causative factor in hepatic encephalopathy, and clinical treatment of hepatic encephalopathy is focused on lowering NH3. Ammonia is a central element in intraorgan nitrogen (N) transport, and modeling the factors that determine blood-NH3 concentration is complicated by the need to account for a variety of reactions carried out in multiple organs. This review presents a detailed quantitative analysis of the major factors determining blood-NH3 homeostasis – the N metabolism of urea, NH3, and amino acids by the liver, gastrointestinal system, muscle, kidney, and brain – with the ultimate goal of creating a model that allows for prediction of blood-NH3 concentration. Although enormous amounts of NH3 are produced during normal liver amino-acid metabolism, this NH3 is completely captured by the urea cycle and does not contribute to blood NH3. While some systemic NH3 derives from renal and muscle metabolism, the primary site of blood-NH3 production is the gastrointestinal tract, as evidenced by portal vein-NH3 concentrations that are about three times that of systemic blood. Three mechanisms, in order of quantitative importance, release NH3 in the gut: 1) hydrolysis of urea by bacterial urease, 2) bacterial protein deamination, and 3) intestinal mucosal glutamine metabolism. Although the colon is conventionally assumed to be the major site of gut-NH3 production, evidence is reviewed that indicates that the stomach (via Helicobacter pylori metabolism) and small intestine and may be of greater importance. In healthy subjects, most of this gut NH3 is removed by the liver before reaching the systemic circulation. Using a quantitative model, loss of this “first-pass metabolism” due to portal collateral circulation can account for the hyperammonemia observed in chronic liver disease, and there is usually no need to implicate hepatocyte malfunction. In contrast, in acute hepatic necrosis, hyperammonemia results from damaged hepatocytes. Although muscle-NH3 uptake is normally negligible, it can become important in severe hyperammonemia. The NH3-lowering actions of intestinal antibiotics (rifaximin) and lactulose are discussed in detail, with particular emphasis on the seeming lack of importance of the frequently emphasized acidifying action of lactulose in the colon.
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Affiliation(s)
- David G Levitt
- Department of Integrative Biology and Physiology, University of Minnesota
| | - Michael D Levitt
- Research Service, Veterans Affairs Medical Center, Minneapolis, MN, USA
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Mary F, Moesseler A, Khodorova N, Foucault-Simonin A, Benamouzig R, Tomé D, Gregory PC, Gaudichon C. Metabolic markers of protein maldigestion after a 15N test meal in minipigs with pancreatic exocrine insufficiency. Am J Physiol Gastrointest Liver Physiol 2018; 314:G223-G230. [PMID: 29074486 DOI: 10.1152/ajpgi.00218.2017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The effect of pancreatic exocrine insufficiency (PEI) on protein malabsorption is little documented, partly due to methodological barriers. We aimed to validate biomarkers of protein malabsorption using a 15N test meal in a minipig model of PEI. Six pancreatic duct-ligated minipigs were used as a model of PEI and four nonoperated animals as a control. All animals were equipped with an ileocecal reentrant cannula. Minipigs were given a test meal containing [15N]casein. The PEI animals repeated the test three times, in the absence of any pancreatic enzymes, or after pancreatic substitution at two levels [ A or B: 7,500 or 75,000 (lipase) and 388 or 3881 (protease) FIP U]. Ileal chyme, urine, and blood were collected postprandially. Nitrogen and 15N were measured in digestive and metabolic pools. We obtained a gradient of ileal protein digestibility from 29 ± 11% in PEI to 89 ± 6% in the controls and a dose- dependent response of enzymes. Insulin and gastric inhibitory polypeptide secretions were decreased by PEI, an effect that was counteracted with the enzymes at level B. The total recovery of 15N in urinary urea and plasma proteins was 14 ± 5.1% in the control group and decreased to 5.5 ± 2.1% by PEI. It was dose dependently restored by the treatment. Both 15N recovery in plasma and urine were correlated to protein digestibility. We confirm that the 15N transfer in those pools is a sensitive marker of protein malabsorption. Nevertheless, an optimization of the test meal conditions would be necessary in the view of implementing a clinical test. NEW & NOTEWORTHY We designed an intervention study to create a gradient of ileal protein digestibility in minipigs with pancreatic exocrine insufficiency and to validate reliable metabolic markers using a 15N oral meal test. 15N recovery in plasma proteins and to a higher extent in urine was sensitive to protein malabsorption. This test is minimally invasive and could be used to reveal protein malabsorption in patients.
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Affiliation(s)
- Florence Mary
- UMR PNCA, AgroParisTech, INRA, Université Paris Saclay , Paris , France
| | - Anne Moesseler
- Institute for Animal Nutrition, University of Veterinary Medicine Hannover, Foundation , Hanover , Germany
| | - Nadezda Khodorova
- UMR PNCA, AgroParisTech, INRA, Université Paris Saclay , Paris , France
| | | | - Robert Benamouzig
- UMR PNCA, AgroParisTech, INRA, Université Paris Saclay , Paris , France
| | - Daniel Tomé
- UMR PNCA, AgroParisTech, INRA, Université Paris Saclay , Paris , France
| | | | - Claire Gaudichon
- UMR PNCA, AgroParisTech, INRA, Université Paris Saclay , Paris , France
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Hu R, Li J, Soomro RN, Wang F, Feng Y, Yang X, Yao J. The 15N-leucine single-injection method allows for determining endogenous losses and true digestibility of amino acids in cecectomized roosters. PLoS One 2017; 12:e0188525. [PMID: 29166671 PMCID: PMC5699825 DOI: 10.1371/journal.pone.0188525] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 11/08/2017] [Indexed: 11/27/2022] Open
Abstract
This study was conducted to assess the influence of dietary protein content in poultry when using the 15N-leucine single-injection method to determine endogenous amino acid losses (EAALs) in poultry. Forty-eight cecectomized roosters (2.39 ± 0.23 kg) were randomly allocated to eight dietary treatments containing protein levels of 0, 3%, 6%, 9%, 12%, 15%, 18% and 21%. Each bird was precisely fed an experimental diet of 25 g/kg of body weight. After feeding, all roosters were subcutaneously injected with a 15N-leucine solution at a dose of 20 mg/kg of body weight. Blood was sampled 23 h after the injection, and excreta samples were continuously collected during the course of the 48-h experiment. The ratio of 15N-enrichment of leucine in crude mucin to free leucine in plasma ranged from 0.664 to 0.763 and remained relatively consistent (P > 0.05) across all treatments. The amino acid (AA) profiles of total endogenous AAs, except isoleucine, alanine, aspartic acid, cysteine, proline and serine, were not influenced (P > 0.05) by dietary protein contents. The predominant endogenous AAs in the excreta were glutamic acid, aspartic acid, threonine, serine and proline. The order of the relative proportions of these predominant AAs also remained relatively constant (P > 0.05). The endogenous losses of total AAs determined with the 15N-leucine single-injection method increased curvilinearly with the dietary protein contents. The true digestibility of most AAs and total AAs was independent of their respective dietary protein levels. Collectively, the 15N-leucine single-injection method is appropriate for determining EAALs and the true digestibility of AAs in poultry fed varying levels of protein-containing ingredients.
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Affiliation(s)
- Rujiu Hu
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Jing Li
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Rab Nawaz Soomro
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Fei Wang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Yan Feng
- College of Life Science, Shanxi Agriculture University, Jinzhong, Shanxi, China
| | - Xiaojun Yang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Junhu Yao
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
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21
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van der Wielen N, Moughan PJ, Mensink M. Amino Acid Absorption in the Large Intestine of Humans and Porcine Models. J Nutr 2017; 147:1493-1498. [PMID: 28615378 DOI: 10.3945/jn.117.248187] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Revised: 03/25/2017] [Accepted: 05/23/2017] [Indexed: 11/14/2022] Open
Abstract
Dietary protein quality has been recognized as a critical issue by international authorities because it can affect important functions of the body. To predict protein quality, the FAO introduced the Digestible Indispensable Amino Acid Score. This score depends on ileal amino acid (AA) digestibility; therefore, the assumption is made that AAs are not absorbed in nutritionally relevant amounts from the large intestine. This article reviews the evidence for this assumption by considering the role of the mammalian large intestine in dietary protein and AA digestion and absorption, with particular reference to adult humans. Although most dietary AAs and peptides are absorbed in the small intestine, substantial amounts can enter the large intestine. Nitrogen is absorbed in the large intestine, and a series of animal experiments indicate a potential small degree of AA absorption. In humans, colonocytes have the capacity for AA absorption because AA transporters are present in the large intestine. The absorption of nutritionally relevant amounts of dietary indispensable AAs and peptides in the human large intestine has not been convincingly demonstrated, however.
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Affiliation(s)
| | - Paul J Moughan
- Riddet Institute, Massey University, Palmerston North, New Zealand
| | - Marco Mensink
- Division of Human Nutrition, Wageningen University, Wageningen, Netherlands; and
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22
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Montoya CA, Rutherfurd SM, Moughan PJ. Ileal Digesta Nondietary Substrates from Cannulated Pigs Are Major Contributors to In Vitro Human Hindgut Short-Chain Fatty Acid Production. J Nutr 2017; 147:264-271. [PMID: 28003537 DOI: 10.3945/jn.116.240564] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 09/19/2016] [Accepted: 11/18/2016] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND It has been assumed that short-chain fatty acids (SCFAs) in the colon originate mainly from dietary fiber fermentation. However, SCFAs in the colon are also produced from the fermentation of nondietary material. OBJECTIVES We aimed to predict the relative contributions of dietary and nondietary substrates in the production of SCFAs with the use of a human fecal inoculum for diets containing kiwifruit as a model fiber. METHODS Terminal ileal digesta were collected from ileal-cannulated male pigs [n = 7; mean ± SD: 41.4 ± 2.98 kg body weight] adapted (44-d feeding) to diets containing either 25 g/kg dry matter (DM) of kiwifruit fiber (KFf) (25 KFf) or 50 g/kg DM of KFf (50 KFf) and then again after receiving a fiber-free diet (n = 14) for a further 7 d. Pigs were used as a model for adult humans for digestion in the upper digestive tract (mouth to the terminal ileum). The ileal digesta (either unfractionated or fractionated into crude mucin and microbial fractions) were fermented in vitro for 24 h with the use of a fresh human fecal inoculum to predict SCFA production in the human hindgut. RESULTS SCFAs of nondietary origin were the main source (65%) of total SCFAs predicted to be produced in the human hindgut. The contribution of SCFAs from KFf was only 26% of the total SCFAs, and that from total dietary material was 35%. The higher contribution of nondietary material to total predicted SCFA production was observed at both dietary fiber concentrations. Predicted SCFA intake from dietary fiber was 76 and 105 mmol/kg diet DM intake for the diets containing 25 KFf and 50 KFf, respectively, and from the nondietary substrates it was 178 and 280 mmol/kg diet DM intake, respectively. CONCLUSION A considerable proportion of the SCFAs produced in the human hindgut seems to be derived from the fermentation of nondietary substrates.
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Affiliation(s)
- Carlos A Montoya
- Massey Institute of Food Science and Technology, and .,Riddet Institute, Massey University, Palmerston North, New Zealand
| | - Shane M Rutherfurd
- Massey Institute of Food Science and Technology, and.,Riddet Institute, Massey University, Palmerston North, New Zealand
| | - Paul J Moughan
- Riddet Institute, Massey University, Palmerston North, New Zealand
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Montoya CA, Henare SJ, Rutherfurd SM, Moughan PJ. Potential misinterpretation of the nutritional value of dietary fiber: correcting fiber digestibility values for nondietary gut-interfering material. Nutr Rev 2016; 74:517-33. [PMID: 27330145 DOI: 10.1093/nutrit/nuw014] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
The aim of this review is to identify the origin and implications of a nondietary material present in digesta and feces that interferes with the determination of dietary fiber in gastrointestinal contents. Negative values for ileal and fecal digestibility of dietary fiber are commonly reported in the literature for monogastric animal species, including humans. As negative values are not possible physiologically, this suggests the existence of a nondietary material in the gastrointestinal contents and feces that interferes with the accurate determination of dietary fiber digestibility when conventional methods of fiber determination are applied. To date, little attention has been given to this nondietary interfering material, which appears to be influenced by the type and concentration of fiber in the diet. Interestingly, estimates of dietary fiber digestibility increase substantially when corrected for the nondietary interfering material, which suggests that currently reported values underestimate the digestibility of dietary fiber and may misrepresent where, in the digestive tract, fermentation of fiber occurs. A new perspective of dietary fiber digestion in the gastrointestinal tract is developing, leading to a better understanding of the contribution of dietary fiber to health.
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Affiliation(s)
- Carlos A Montoya
- C.A. Montoya, S.J. Henare, and S.M. Rutherfurd are with the Massey Institute of Food Science and Technology, Massey University, Palmerston North, New Zealand.C.A. Montoya, S.J. Henare, S.M. Rutherfurd, and P.J. Moughan are with the Riddet Institute, Massey University, Palmerston North, New Zealand.
| | - Sharon J Henare
- C.A. Montoya, S.J. Henare, and S.M. Rutherfurd are with the Massey Institute of Food Science and Technology, Massey University, Palmerston North, New Zealand.C.A. Montoya, S.J. Henare, S.M. Rutherfurd, and P.J. Moughan are with the Riddet Institute, Massey University, Palmerston North, New Zealand
| | - Shane M Rutherfurd
- C.A. Montoya, S.J. Henare, and S.M. Rutherfurd are with the Massey Institute of Food Science and Technology, Massey University, Palmerston North, New Zealand.C.A. Montoya, S.J. Henare, S.M. Rutherfurd, and P.J. Moughan are with the Riddet Institute, Massey University, Palmerston North, New Zealand
| | - Paul J Moughan
- C.A. Montoya, S.J. Henare, and S.M. Rutherfurd are with the Massey Institute of Food Science and Technology, Massey University, Palmerston North, New Zealand.C.A. Montoya, S.J. Henare, S.M. Rutherfurd, and P.J. Moughan are with the Riddet Institute, Massey University, Palmerston North, New Zealand
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Dave LA, Hayes M, Mora L, Montoya CA, Moughan PJ, Rutherfurd SM. Gastrointestinal Endogenous Protein-Derived Bioactive Peptides: An in Vitro Study of Their Gut Modulatory Potential. Int J Mol Sci 2016; 17:482. [PMID: 27043546 PMCID: PMC4848938 DOI: 10.3390/ijms17040482] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Revised: 03/15/2016] [Accepted: 03/15/2016] [Indexed: 02/07/2023] Open
Abstract
A recently proposed paradigm suggests that, like their dietary counterparts, digestion of gastrointestinal endogenous proteins (GEP) may also produce bioactive peptides. With an aim to test this hypothesis, in vitro digests of four GEP namely; trypsin (TRYP), lysozyme (LYS), mucin (MUC), serum albumin (SA) and a dietary protein chicken albumin (CA) were screened for their angiotensin-I converting (ACE-I), renin, platelet-activating factor-acetylhydrolase (PAF-AH) and dipeptidyl peptidase-IV inhibitory (DPP-IV) and antioxidant potential following simulated in vitro gastrointestinal digestion. Further, the resultant small intestinal digests were enriched to obtain peptides between 3-10 kDa in size. All in vitro digests of the four GEP were found to inhibit ACE-I compared to the positive control captopril when assayed at a concentration of 1 mg/mL, while the LYS < 3-kDa permeate fraction inhibited renin by 40% (±1.79%). The LYS < 10-kDa fraction inhibited PAF-AH by 39% (±4.34%), and the SA < 3-kDa fraction inhibited DPP-IV by 45% (±1.24%). The MUC < 3-kDa fraction had an ABTS-inhibition antioxidant activity of 150 (±24.79) µM trolox equivalent and the LYS < 10-kDa fraction inhibited 2,2-Diphenyl-1-picrylhydrazyl (DPPH) by 54% (±1.62%). Moreover, over 190 peptide-sequences were identified from the bioactive GEP fractions. The findings of the present study indicate that GEP are a significant source of bioactive peptides which may influence gut function.
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Affiliation(s)
- Lakshmi A Dave
- The Riddet Institute, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand.
- Teagasc, The Irish Agricultural and Food Development Authority, Food BioSciences Department, Ashtown, Dublin 15, Ireland.
| | - Maria Hayes
- Teagasc, The Irish Agricultural and Food Development Authority, Food BioSciences Department, Ashtown, Dublin 15, Ireland.
| | - Leticia Mora
- Instituto de Agroquı́mica y Tecnologı́a de Alimentos (CSIC), Avenida Agustín Escardino 7, 46980 Paterna, Valencia 46002, Spain.
| | - Carlos A Montoya
- The Riddet Institute, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand.
| | - Paul J Moughan
- The Riddet Institute, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand.
| | - Shane M Rutherfurd
- The Riddet Institute, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand.
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Dave LA, Hayes M, Montoya CA, Rutherfurd SM, Moughan PJ. Human gut endogenous proteins as a potential source of angiotensin-I-converting enzyme (ACE-I)-, renin inhibitory and antioxidant peptides. Peptides 2016; 76:30-44. [PMID: 26617077 DOI: 10.1016/j.peptides.2015.11.003] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Revised: 10/07/2015] [Accepted: 11/19/2015] [Indexed: 01/17/2023]
Abstract
It is well known that endogenous bioactive proteins and peptides play a substantial role in the body's first line of immunological defence, immune-regulation and normal body functioning. Further, the peptides derived from the luminal digestion of proteins are also important for body function. For example, within the peptide database BIOPEP (http://www.uwm.edu.pl/biochemia/index.php/en/biopep) 12 endogenous antimicrobial and 64 angiotensin-I-converting enzyme (ACE-I) inhibitory peptides derived from human milk and plasma proteins are listed. The antimicrobial peptide database (http://aps.unmc.edu/AP/main.php) lists over 111 human host-defence peptides. Several endogenous proteins are secreted in the gut and are subject to the same gastrointestinal digestion processes as food proteins derived from the diet. The human gut endogenous proteins (GEP) include mucins, serum albumin, digestive enzymes, hormones, and proteins from sloughed off epithelial cells and gut microbiota, and numerous other secreted proteins. To date, much work has been carried out regarding the health altering effects of food-derived bioactive peptides but little attention has been paid to the possibility that GEP may also be a source of bioactive peptides. In this review, we discuss the potential of GEP to constitute a gut cryptome from which bioactive peptides such as ACE-I inhibitory, renin inhibitory and antioxidant peptides may be derived.
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Affiliation(s)
- Lakshmi A Dave
- Massey Institute of Food Science and Technology, Massey University, Palmerston North, New Zealand; Teagasc, The Irish Agricultural and Food Development Authority, Food BioSciences Department, Ashtown, D 15 Dublin, Ireland
| | - Maria Hayes
- Teagasc, The Irish Agricultural and Food Development Authority, Food BioSciences Department, Ashtown, D 15 Dublin, Ireland
| | - Carlos A Montoya
- Massey Institute of Food Science and Technology, Massey University, Palmerston North, New Zealand
| | - Shane M Rutherfurd
- Massey Institute of Food Science and Technology, Massey University, Palmerston North, New Zealand.
| | - Paul J Moughan
- Massey Institute of Food Science and Technology, Massey University, Palmerston North, New Zealand
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Montoya CA, Rutherfurd SM, Moughan PJ. Nondietary Gut Materials Interfere with the Determination of Dietary Fiber Digestibility in Growing Pigs When Using the Prosky Method. J Nutr 2015; 145:1966-72. [PMID: 26063063 DOI: 10.3945/jn.115.212639] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2015] [Accepted: 05/14/2015] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Reported negative ileal and total tract dietary fiber (DF) digestibility values are physiologically untenable and suggest the presence of nondietary material in the gut contents that interferes with the DF determination. OBJECTIVE The objective of this study was to demonstrate the importance of interfering material (IM) when the Prosky method was used to determine DF digestibility. METHODS Fourteen pigs (41.6 ± 3.0 kg) were surgically implanted with ileal T-cannulas. A semisynthetic fiber-free diet and 2 semisynthetic diets containing kiwifruit as the sole fiber source [25 or 50 g fiber/kg dry matter (DM)] were prepared. Titanium dioxide was used as an indigestible marker. Pigs were fed the kiwifruit-containing diets (n=7 per diet) for 44 d, followed by the fiber-free diet (n=14) for 7 d. Ileal digesta and feces were collected over 3 d, starting on days 42 and 49. The flow of IM and the soluble, insoluble, and total DF digestibility were determined. RESULTS Considerable amounts of IM were present when the Prosky method was applied to ileal digesta (12 g/kg DM intake) and feces (28 g/kg DM intake) collected from pigs fed the fiber-free diet after adaptation to the diet containing 50 g/kg DM of fiber. The pigs adapted to the highest fiber concentration had 0.9- and 0.7-fold greater ileal and fecal IM flows than their counterparts adapted to the lowest concentration. In the ileal digesta, crude mucin was the main IM source in the soluble DF fraction (66%). In the ileal digesta and feces, microbial cells were the main IM source in the insoluble DF fraction. The determined ileal soluble DF and total tract insoluble DF digestibilities increased by 44-54% and 78% respectively after correction for IM (P < 0.001). CONCLUSIONS Large amounts of IM are present in ileal digesta and feces of pigs when fiber is determined with the Prosky method, leading to a marked underestimation.
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Affiliation(s)
- Carlos A Montoya
- Riddet Institute, Massey University, Palmerston North, New Zealand
| | | | - Paul J Moughan
- Riddet Institute, Massey University, Palmerston North, New Zealand
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Rutherfurd SM, Cui J, Goroncy AK, Moughan PJ. Dietary protein structure affects endogenous ileal amino acids but not true ileal amino acid digestibility in growing male rats. J Nutr 2015; 145:193-8. [PMID: 25644337 DOI: 10.3945/jn.114.198283] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND The amount of endogenous, as opposed to undigested dietary, protein in digesta is a measure of fundamental interest related to gut physiology and function. OBJECTIVE The objective of this study was to determine whether alimentation with proteins having differing amino acid compositions influenced endogenous ileal amino acids (EIAAs) and true ileal amino acid digestibility (TIAAD) values. METHODS Male rats (n = 8) were fed a purified diet containing 100 g/kg of 1 of 5 protein hydrolysates, each derived from a different semipurified intact protein source [gelatin, beef muscle (BM), casein, soy protein isolate (SPI), and lactalbumin] devoid of antinutritional factors or fiber. The rats were fed their respective hydrolysate-based diet for 1 d after receiving the same diet but containing the corresponding intact protein source for 7 d. Titanium dioxide was used as an indigestible marker. Ileal digesta were collected after the rats were killed, and EIAAs were determined (precipitate + retentate) after centrifugation and ultrafiltration of the digesta. The TIAAD values of the intact protein sources were determined using EIAA flows based on each protein hydrolysate. RESULTS Mean EIAA flows differed (P < 0.05) across protein hydrolysates for most amino acids, with the mean ± SEM EIAA flows across amino acids being 262 ± 17, 253 ± 12, 248 ± 18, 226 ± 14, and 191 ± 20 mg/kg dry matter intake for the gelatin, BM, casein, SPI, and lactalbumin hydrolysates, respectively. The only difference (P < 0.05) for the mean EIAA flows across amino acids within each protein hydrolysate was observed between gelatin (262 ± 17 mg/kg) and lactalbumin (191 ± 20 mg/kg) hydrolysates. Except for Trp (P < 0.001) in gelatin and lactalbumin hydrolysates, EIAA flows determined using the casein hydrolysate were not different (P ≥ 0.05) from EIAA flows determined using the other protein hydrolysates. TIAAD values were not generally different (P ≥ 0.05) regardless of the hydrolysate used to determine the EIAA flows. CONCLUSIONS Protein source affected EIAA flows, although the differences had little effect on TIAAD. Enzyme hydrolyzed casein is a suitable model hydrolysate for determining TIAAD with the enzyme-hydrolyzed protein-ultrafiltration technique.
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Affiliation(s)
| | - Jian Cui
- Riddet Institute, Massey University, Palmerston North, New Zealand
| | | | - Paul J Moughan
- Riddet Institute, Massey University, Palmerston North, New Zealand
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Liu X, Blouin JM, Santacruz A, Lan A, Andriamihaja M, Wilkanowicz S, Benetti PH, Tomé D, Sanz Y, Blachier F, Davila AM. High-protein diet modifies colonic microbiota and luminal environment but not colonocyte metabolism in the rat model: the increased luminal bulk connection. Am J Physiol Gastrointest Liver Physiol 2014; 307:G459-70. [PMID: 24970777 DOI: 10.1152/ajpgi.00400.2013] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
High-protein diets are used for body weight reduction, but consequences on the large intestine ecosystem are poorly known. Here, rats were fed for 15 days with either a normoproteic diet (NP, 14% protein) or a hyperproteic-hypoglucidic isocaloric diet (HP, 53% protein). Cecum and colon were recovered for analysis. Short- and branched-chain fatty acids, as well as lactate, succinate, formate, and ethanol contents, were markedly increased in the colonic luminal contents of HP rats (P < 0.05 or less) but to a lower extent in the cecal luminal content. This was associated with reduced concentrations of the Clostridium coccoides and C. leptum groups and Faecalibacterium prausnitzii in both the cecum and colon (P < 0.05 or less). In addition, the microbiota diversity was found to be higher in the cecum of HP rats but was lower in the colon compared with NP rats. In HP rats, the colonic and cecal luminal content weights were markedly higher than in NP rats (P < 0.001), resulting in similar butyrate, acetate, and propionate concentrations. Accordingly, the expression of monocarboxylate transporter 1 and sodium monocarboxylate transporter 1 (which is increased by higher butyrate concentration) as well as the colonocyte capacity for butyrate oxidation were not modified by the HP diet, whereas the amount of butyrate in feces was increased (P < 0.01). It is concluded that an increased bulk in the large intestine content following HP diet consumption allows maintenance in the luminal butyrate concentration and thus its metabolism in colonocytes despite modified microbiota composition and increased substrate availability.
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Affiliation(s)
- Xinxin Liu
- UMR914 Institut National de la Recherche Agronomique/AgroParisTech, Nutrition Physiology and Ingestive Behavior, Paris, France; and
| | - Jean-Marc Blouin
- UMR914 Institut National de la Recherche Agronomique/AgroParisTech, Nutrition Physiology and Ingestive Behavior, Paris, France; and
| | - Arlette Santacruz
- Microbial Ecophysiology and Nutrition Research Group, Institute of Agrochemistry and Food Technology, Spanish National Research Council, Valencia, Spain
| | - Annaïg Lan
- UMR914 Institut National de la Recherche Agronomique/AgroParisTech, Nutrition Physiology and Ingestive Behavior, Paris, France; and
| | - Mireille Andriamihaja
- UMR914 Institut National de la Recherche Agronomique/AgroParisTech, Nutrition Physiology and Ingestive Behavior, Paris, France; and
| | - Sabina Wilkanowicz
- Microbial Ecophysiology and Nutrition Research Group, Institute of Agrochemistry and Food Technology, Spanish National Research Council, Valencia, Spain
| | - Pierre-Henri Benetti
- UMR914 Institut National de la Recherche Agronomique/AgroParisTech, Nutrition Physiology and Ingestive Behavior, Paris, France; and
| | - Daniel Tomé
- UMR914 Institut National de la Recherche Agronomique/AgroParisTech, Nutrition Physiology and Ingestive Behavior, Paris, France; and
| | - Yolanda Sanz
- Microbial Ecophysiology and Nutrition Research Group, Institute of Agrochemistry and Food Technology, Spanish National Research Council, Valencia, Spain
| | - François Blachier
- UMR914 Institut National de la Recherche Agronomique/AgroParisTech, Nutrition Physiology and Ingestive Behavior, Paris, France; and
| | - Anne-Marie Davila
- UMR914 Institut National de la Recherche Agronomique/AgroParisTech, Nutrition Physiology and Ingestive Behavior, Paris, France; and
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Dave LA, Montoya CA, Rutherfurd SM, Moughan PJ. Gastrointestinal endogenous proteins as a source of bioactive peptides--an in silico study. PLoS One 2014; 9:e98922. [PMID: 24901416 PMCID: PMC4047039 DOI: 10.1371/journal.pone.0098922] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Accepted: 05/08/2014] [Indexed: 12/05/2022] Open
Abstract
Dietary proteins are known to contain bioactive peptides that are released during digestion. Endogenous proteins secreted into the gastrointestinal tract represent a quantitatively greater supply of protein to the gut lumen than those of dietary origin. Many of these endogenous proteins are digested in the gastrointestinal tract but the possibility that these are also a source of bioactive peptides has not been considered. An in silico prediction method was used to test if bioactive peptides could be derived from the gastrointestinal digestion of gut endogenous proteins. Twenty six gut endogenous proteins and seven dietary proteins were evaluated. The peptides present after gastric and intestinal digestion were predicted based on the amino acid sequence of the proteins and the known specificities of the major gastrointestinal proteases. The predicted resultant peptides possessing amino acid sequences identical to those of known bioactive peptides were identified. After gastrointestinal digestion (based on the in silico simulation), the total number of bioactive peptides predicted to be released ranged from 1 (gliadin) to 55 (myosin) for the selected dietary proteins and from 1 (secretin) to 39 (mucin-5AC) for the selected gut endogenous proteins. Within the intact proteins and after simulated gastrointestinal digestion, angiotensin converting enzyme (ACE)-inhibitory peptide sequences were the most frequently observed in both the dietary and endogenous proteins. Among the dietary proteins, after in silico simulated gastrointestinal digestion, myosin was found to have the highest number of ACE-inhibitory peptide sequences (49 peptides), while for the gut endogenous proteins, mucin-5AC had the greatest number of ACE-inhibitory peptide sequences (38 peptides). Gut endogenous proteins may be an important source of bioactive peptides in the gut particularly since gut endogenous proteins represent a quantitatively large and consistent source of protein.
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Affiliation(s)
- Lakshmi A. Dave
- Riddet Institute, Massey University, Palmerston North, New Zealand
| | | | | | - Paul J. Moughan
- Riddet Institute, Massey University, Palmerston North, New Zealand
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Miner-Williams W, Deglaire A, Benamouzig R, Fuller MF, Tomé D, Moughan PJ. Endogenous proteins in the ileal digesta of adult humans given casein-, enzyme-hydrolyzed casein- or crystalline amino-acid-based diets in an acute feeding study. Eur J Clin Nutr 2014; 68:363-9. [PMID: 24398648 DOI: 10.1038/ejcn.2013.270] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2013] [Revised: 10/06/2013] [Accepted: 11/18/2013] [Indexed: 11/09/2022]
Abstract
BACKGROUND/OBJECTIVES To ascertain if the form of dietary nitrogen (free amino acids (AA), small peptides, or intact protein) affects the endogenous nitrogen containing substances lost from the upper digestive tract of humans. SUBJECTS/METHODS Digesta were collected via a naso-ileal tube from the terminal ileum of 16 adult humans in a single parallel study following an acute feeding regimen. Subjects were given an iso-nitrogenous and isocaloric test meal containing 150 g of casein (CAS) (n=6), enzyme-hydrolyzed casein (HCAS) (n=5) or crystalline AA (n=5) dissolved in 550 ml of water, as the sole sources of nitrogen. RESULTS The mean concentrations and flows of total nitrogen, protein nitrogen, and soluble protein nitrogen passing the terminal ileum were significantly higher (P <0.01) for the CAS and HCAS test-meal groups compared to the AA meal group. Dietary CAS and HCAS had a considerable influence on digesta mucin concentrations and flows compared to free AA (+41%). Only 3-4% of the total nitrogen remained unidentified. CONCLUSIONS The form of dietary nitrogen (protein, small peptides or free AA) had an acute effect upon the secretion or reabsorption of endogenous proteins in the small intestine of healthy humans, as evident from significant differences in both the quantity and composition of the proteins found in digesta at the end of the ileum.
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Affiliation(s)
- W Miner-Williams
- Riddet Institute, Massey University, Palmerston North, New Zealand
| | - A Deglaire
- The Unité de Recherche en Epidémiologie Nutritionnelle, L'unité mixte de recherche French Institute of Agricultural Research 1125, Institut national de la santé et de la recherche médicale 557, Conservatoire National des Arts et Métiers, Universite' Paris 13, Paris, France
| | - R Benamouzig
- The Gastroenterology Unit, Le Centre de Recherche en Nutrition Humaine d'Ile-de-France, Assistance Publique-Hôpitaux de Paris, University Paris 13, Hôpital Avicenne, Paris, France
| | - M F Fuller
- The State University of New York, Stony Brook, NY, USA
| | - D Tomé
- French Institute of Agricultural Research, Le Centre de Recherche en Nutrition Humaine- d'Ile-de-France, L'unité mixte de recherche 914 Nutrition Physiology and Ingestive Behavior, Paris, France
| | - P J Moughan
- Riddet Institute, Massey University, Palmerston North, New Zealand
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Abstract
Food-derived bioactive peptides are regarded as important modulators of several physiological processes occurring both systemically and locally within the gastrointestinal tract (GIT). However, the concentrations of food-derived bioactive peptides in the GIT, and therefore attendant physiological effects, are likely to be highly variable given the wide variation in the type and amount of dietary protein consumed either during the day or on a day-to-day basis. In contrast, gut endogenous proteins (e.g. cell proteins, mucin, serum albumin and digestive enzymes) are a consistent and significant potential source of peptides for the GIT. With up to 80% of gut endogenous proteins being digested in the GIT, it is possible that a wide range of peptides is generated, but until now the significance of the gut endogenous proteins as a source of bioactive peptides has not been considered. A hypothesis is promulgated that the gut endogenous proteins may have a hidden role as a consistent and quantitatively important source of bioactive peptides in the GIT.
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Protein Digestion and Absorption of Peptides and Amino Acids. Amino Acids 2013. [DOI: 10.1201/b14661-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Bengmark S. Nutrition of the critically ill — a 21st-century perspective. Nutrients 2013; 5:162-207. [PMID: 23344250 PMCID: PMC3571643 DOI: 10.3390/nu5010162] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2012] [Revised: 12/17/2012] [Accepted: 12/24/2012] [Indexed: 02/07/2023] Open
Abstract
Health care-induced diseases constitute a fast-increasing problem. Just one type of these health care-associated infections (HCAI) constitutes the fourth leading cause of death in Western countries. About 25 million individuals worldwide are estimated each year to undergo major surgery, of which approximately 3 million will never return home from the hospital. Furthermore, the quality of life is reported to be significantly impaired for the rest of the lives of those who, during their hospital stay, suffered life-threatening infections/sepsis. Severe infections are strongly associated with a high degree of systemic inflammation in the body, and intimately associated with significantly reduced and malfunctioning GI microbiota, a condition called dysbiosis. Deranged composition and function of the gastrointestinal microbiota, occurring from the mouth to the anus, has been found to cause impaired ability to maintain intact mucosal membrane functions and prevent leakage of toxins - bacterial endotoxins, as well as whole bacteria or debris of bacteria, the DNA of which are commonly found in most cells of the body, often in adipocytes of obese individuals or in arteriosclerotic plaques. Foods rich in proteotoxins such as gluten, casein and zein, and proteins, have been observed to have endotoxin-like effects that can contribute to dysbiosis. About 75% of the food in the Western diet is of limited or no benefit to the microbiota in the lower gut. Most of it, comprised specifically of refined carbohydrates, is already absorbed in the upper part of the GI tract, and what eventually reaches the large intestine is of limited value, as it contains only small amounts of the minerals, vitamins and other nutrients necessary for maintenance of the microbiota. The consequence is that the microbiota of modern humans is greatly reduced, both in terms of numbers and diversity when compared to the diets of our paleolithic forebears and the individuals living a rural lifestyle today. It is the artificial treatment provided in modern medical care - unfortunately often the only alternative provided - which constitute the main contributors to a poor outcome. These treatments include artificial ventilation, artificial nutrition, hygienic measures, use of skin-penetrating devices, tubes and catheters, frequent use of pharmaceuticals; they are all known to severely impair the microbiomes in various locations of the body, which, to a large extent, are ultimately responsible for a poor outcome. Attempts to reconstitute a normal microbiome by supply of probiotics have often failed as they are almost always undertaken as a complement to - and not as an alternative to - existing treatment schemes, especially those based on antibiotics, but also other pharmaceuticals.
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Affiliation(s)
- Stig Bengmark
- Division of Surgery & Interventional Science, University College London, 4th floor, 74 Huntley Street, London, WC1E 6AU, UK.
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Bengmark S. Nutrition of the critically ill - emphasis on liver and pancreas. Hepatobiliary Surg Nutr 2012; 1:25-52. [PMID: 24570901 PMCID: PMC3924628 DOI: 10.3978/j.issn.2304-3881.2012.10.14] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2012] [Accepted: 10/25/2012] [Indexed: 12/13/2022]
Abstract
About 25 million individuals undergo high risk surgery each year. Of these about 3 million will never return home from hospital, and the quality of life for many of those who return is often significantly impaired. Furthermore, many of those who manage to leave hospital have undergone severe life-threatening complications, mostly infections/sepsis. The development is strongly associated with the level of systemic inflammation in the body, which again is entirely a result of malfunctioning GI microbiota, a condition called dysbiosis, with deranged composition and function of the gastrointestinal microbiota from the mouth to the anus and impaired ability to maintain intact mucosal membrane functions and prevent leakage of toxins-bacterial endotoxins and whole or debris of bacteria, but also foods containing proteotoxins gluten, casein and zein and heat-induced molecules such as advanced glycation end products (AGEs) and advanced lipoxidation end products (ALEs). Markedly lower total anaerobic bacterial counts, particularly of the beneficial Bifidobacterium and Lactobacillus and higher counts of total facultative anaerobes such as Staphylococcus and Pseudomonas are often observed when analyzing the colonic microbiota. In addition Gram-negative facultative anaerobes are commonly identified microbial organisms in mesenteric lymph nodes and at serosal "scrapings" at laparotomy in patients suffering what is called "Systemic inflammation response system" (SIRS). Clearly the outcome is influenced by preexisting conditions in those undergoing surgery, but not to the extent as one could expect. Several studies have for example been unable to find significant influence of pre-existing obesity. The outcome seems much more to be related to the life-style of the individual and her/his "maintenance" of the microbiota e.g., size and diversity of microbiota, normal microbiota, eubiosis, being highly preventive. About 75% of the food Westerners consume does not benefit microbiota in the lower gut. Most of it, refined carbohydrates, is already absorbed in the upper part of the GI tract, and of what reaches the large intestine is of limited value containing less minerals, less vitamins and other nutrients important for maintenance of the microbiota. The consequence is that the microbiota of modern man has a much reduced size and diversity in comparison to what our Palelithic forefathers had, and individuals living a rural life have today. It is the artificial treatment provided by modern care, unfortunately often the only alternative, which belongs to the main contributor to poor outcome, among them; artificial ventilation, artificial nutrition, hygienic measures, use of skin penetrating devices, tubes and catheters, frequent use of pharmaceuticals, all known to significantly impair the total microbiome of the body and dramatically contribute to poor outcome. Attempts to reconstitute a normal microbiome have often failed as they have always been undertaken as a complement to and not an alternative to existing treatment schemes, especially treatments with antibiotics. Modern nutrition formulas are clearly too artificial as they are based on mixture of a variety of chemicals, which alone or together induce inflammation. Alternative formulas, based on regular food ingredients, especially rich in raw fresh greens, vegetables and fruits and with them healthy bacteria are suggested to be developed and tried.
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Affiliation(s)
- Stig Bengmark
- Division of Surgery & Interventional Science, University College London, London, WC1E 6AU, United Kingdom
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