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Schlicht K, Pape L, Rohmann N, Knappe C, Epe J, Geisler C, Pohlschneider D, Brodesser S, Kruse L, Rohlfing ME, Hartmann K, Türk K, Marquardt J, Beckmann J, von Schönfels W, Beckmann A, Wietzke-Braun P, Schulte DM, Hollstein T, Demetrowitsch T, Jensen-Kroll J, Brix F, Schreiber S, Franke A, Schwarz K, Waschina S, Laudes M. Prediabetes and type 2 diabetes but not obesity are associated with alterations in bile acid related gut microbe-microbe and gut microbe-host community metabolism. Gut Microbes 2025; 17:2474143. [PMID: 40045464 PMCID: PMC11901388 DOI: 10.1080/19490976.2025.2474143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 01/20/2025] [Accepted: 02/25/2025] [Indexed: 03/14/2025] Open
Abstract
The interplay between bile acids (BAs) and metabolic diseases has gained importance in recent years, with a variety of studies investigating their relationship with diverging results. Therefore, in the present study we performed a detailed analysis of BA metabolism in 492 subjects with different metabolic phenotypes. Besides microbiomics and metabolomics this investigation included in silico analysis of community metabolism to examine metabolic interchange between different microbes as well as microbes and the human host. Our findings revealed distinct changes in the BA profiles of patients with diabetes and prediabetes, whereas obesity alone had no influence on circulating BAs. Impaired glycemic control led to increased circulating BAs, a shift toward more secondary BAs, and an increase in the ratio of glycine to taurine-conjugated BAs. Additional analyses revealed that the ratio of glycine to taurine conjugation demonstrated variations between the single BAs, cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA), regardless of the metabolic status, with CA having a higher fraction of taurine conjugation. Furthermore, we found that microbiome alterations are associated with BAs, independent of diabetes or obesity. Analysis of microbial community metabolism revealed differential relative pathway abundance in relation to diabetes, particularly those related to membrane and polyamine synthesis. Increased bacterial cross-feeding of polyamines, galactose, and D-arabinose also coincided with an increase in BA. Notably, our serum metabolome analysis mirrored several of the previously in silico predicted exchanged metabolites, especially amino acid metabolism. Therefore, targeting BA metabolism may be a future approach for the treatment of metabolic diseases, especially prediabetes and type 2 diabetes.
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Affiliation(s)
- Kristina Schlicht
- Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Lea Pape
- Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Nathalie Rohmann
- Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Carina Knappe
- Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Johannes Epe
- Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Corinna Geisler
- Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Daniela Pohlschneider
- Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Susanne Brodesser
- Faculty of Medicine and University Hospital of Cologne, Cluster of Excellence Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany
| | - Lucy Kruse
- Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Maria-Elisabeth Rohlfing
- Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Katharina Hartmann
- Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Kathrin Türk
- Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Jens Marquardt
- Department of Internal Medicine 1, University Medical Center Schleswig-Holstein, Lübeck, Germany
| | - Jan Beckmann
- Department of General and Abdominal Surgery, University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany
| | - Witigo von Schönfels
- Department of General and Abdominal Surgery, University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany
| | - Alexia Beckmann
- Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Perdita Wietzke-Braun
- Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Dominik M. Schulte
- Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Tim Hollstein
- Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Tobias Demetrowitsch
- Division of Food Technology, Institute of Human Nutrition and Food Science, Kiel University, Kiel, Germany
| | - Julia Jensen-Kroll
- Division of Food Technology, Institute of Human Nutrition and Food Science, Kiel University, Kiel, Germany
| | - Fynn Brix
- Division of Food Technology, Institute of Human Nutrition and Food Science, Kiel University, Kiel, Germany
| | - Stefan Schreiber
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
| | - Andre Franke
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
| | - Karin Schwarz
- Division of Food Technology, Institute of Human Nutrition and Food Science, Kiel University, Kiel, Germany
| | - Silvio Waschina
- Division of Food Technology, Institute of Human Nutrition and Food Science, Kiel University, Kiel, Germany
| | - Matthias Laudes
- Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein, Kiel, Germany
- Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany
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Steinert RE, Rehman A, Sadabad MS, Milanese A, Wittwer-Schegg J, Burton JP, Spooren A. Microbial micronutrient sharing, gut redox balance and keystone taxa as a basis for a new perspective to solutions targeting health from the gut. Gut Microbes 2025; 17:2477816. [PMID: 40090884 PMCID: PMC11913388 DOI: 10.1080/19490976.2025.2477816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 02/05/2025] [Accepted: 03/05/2025] [Indexed: 03/18/2025] Open
Abstract
In health, the gut microbiome functions as a stable ecosystem maintaining overall balance and ensuring its own survival against environmental stressors through complex microbial interaction. This balance and protection from stressors is maintained through interactions both within the bacterial ecosystem as well as with its host. As a consequence, the gut microbiome plays a critical role in various physiological processes including maintaining the structure and function of the gut barrier, educating the gut immune system, and modulating the gut motor, digestive/absorptive, as well as neuroendocrine system all of which are crucial for human health and disease pathogenesis. Pre- and probiotics, widely available and clinically established, offer various health benefits primarily by beneficially modulating the gut microbiome. However, their clinical outcomes can vary significantly due to differences in host physiology, diets, individual microbiome compositions, and other environmental factors. This perspective paper highlights emerging scientific insights into the importance of microbial micronutrient sharing, gut redox balance, keystone species, and the gut barrier in maintaining a diverse and functional microbial ecosystem, and their relevance to human health. We propose a novel approach that targets microbial ecosystems and keystone taxa performance by supplying microbial micronutrients in the form of colon-delivered vitamins, and precision prebiotics [e.g. human milk oligosaccharides (HMOs) or synthetic glycans] as components of precisely tailored ingredient combinations to optimize human health. Such a strategy may effectively support and stabilize microbial ecosystems, providing a more robust and consistent approach across various individuals and environmental conditions, thus, overcoming the limitations of current single biotic solutions.
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Affiliation(s)
- Robert E. Steinert
- Health, Nutrition & Care (HNC), Dsm-Firmenich, Kaiseraugst, Switzerland
- Department of Surgery and Transplantation, University Hospital Zurich (USZ) and University of Zurich (UZH), Zürich, Switzerland
| | - Ateequr Rehman
- Health, Nutrition & Care (HNC), Dsm-Firmenich, Kaiseraugst, Switzerland
| | | | - Alessio Milanese
- Data Science, Science & Research, Dsm-Firmenich, Delft, Netherlands
| | | | - Jeremy P. Burton
- Department of Microbiology and Immunology, The University of Western Ontario, London, Canada
| | - Anneleen Spooren
- Health, Nutrition & Care (HNC), Dsm-Firmenich, Kaiseraugst, Switzerland
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Zheng ZQ, Shen L, Zhao LM, Ji HF. B vitamins as adjunct therapies for depressive disorder. Trends Endocrinol Metab 2025:S1043-2760(25)00082-7. [PMID: 40374496 DOI: 10.1016/j.tem.2025.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 04/07/2025] [Accepted: 04/10/2025] [Indexed: 05/17/2025]
Abstract
The rising prevalence of depressive disorder worldwide requires better interventional avenues. B vitamins are gaining increasing interest as potential therapeutic approaches in this context given current evidence for a bidirectional association between B vitamin deficiency and depressive disorder. We discuss how B vitamins and B vitamin-associated probiotic supplementation may represent an effective adjunctive treatment for depression, and highlight the key metabolic mechanisms involved. We also provide a perspective on the future of this field and advocate for further high-quality clinical trials to assess the benefits of B vitamins in this context and optimize their clinical implementation.
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Affiliation(s)
- Zi-Qing Zheng
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo 255000, China; Institute of Food and Drug Research for One Health, School of Food Engineering, Ludong University, Yantai 264025, China
| | - Liang Shen
- Institute of Food and Drug Research for One Health, School of Food Engineering, Ludong University, Yantai 264025, China.
| | - Li-Ming Zhao
- State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, Shanghai 200237, China.
| | - Hong-Fang Ji
- Institute of Food and Drug Research for One Health, School of Food Engineering, Ludong University, Yantai 264025, China.
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Andreani NA, Unterweger D, Schreiber S, Baines JF. Evolutionary Medicine for Chronic Inflammatory Diseases of the Gut: More Than a Clinical Fantasy? Gastroenterology 2025; 168:439-443. [PMID: 39426489 DOI: 10.1053/j.gastro.2024.10.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 10/11/2024] [Accepted: 10/15/2024] [Indexed: 10/21/2024]
Affiliation(s)
- Nadia Andrea Andreani
- Section of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Kiel, Germany; Max Planck Institute for Evolutionary Biology, Plön, Germany
| | - Daniel Unterweger
- Section of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Kiel, Germany; Max Planck Institute for Evolutionary Biology, Plön, Germany
| | - Stefan Schreiber
- Institute of Clinical Molecular Biology, Department of Medicine I, University Medical Center Schleswig-Holstein, Kiel University, Kiel, Germany; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel University, Kiel, Germany
| | - John F Baines
- Section of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Kiel, Germany; Max Planck Institute for Evolutionary Biology, Plön, Germany
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Dwibedi C, Axelsson AS, Abrahamsson B, Fahey JW, Asplund O, Hansson O, Ahlqvist E, Tremaroli V, Bäckhed F, Rosengren AH. Effect of broccoli sprout extract and baseline gut microbiota on fasting blood glucose in prediabetes: a randomized, placebo-controlled trial. Nat Microbiol 2025; 10:681-693. [PMID: 39929977 PMCID: PMC11879859 DOI: 10.1038/s41564-025-01932-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 01/13/2025] [Indexed: 03/06/2025]
Abstract
More effective treatments are needed for impaired fasting glucose or glucose intolerance, known as prediabetes. Sulforaphane is an isothiocyanate that reduces hepatic gluconeogenesis in individuals with type 2 diabetes and is well tolerated when provided as a broccoli sprout extract (BSE). Here we report a randomized, double-blind, placebo-controlled trial in which drug-naive individuals with prediabetes were treated with BSE (n = 35) or placebo (n = 39) once daily for 12 weeks. The primary outcome was a 0.3 mmol l-1 reduction in fasting blood glucose compared with placebo from baseline to week 12. Gastro-intestinal side effects but no severe adverse events were observed in response to treatment. BSE did not meet the prespecified primary outcome, and the overall effect in individuals with prediabetes was a 0.2 mmol l-1 reduction in fasting blood glucose (95% confidence interval -0.44 to -0.01; P = 0.04). Exploratory analyses to identify subgroups revealed that individuals with mild obesity, low insulin resistance and reduced insulin secretion had a pronounced response (0.4 mmol l-1 reduction) and were consequently referred to as responders. Gut microbiota analysis further revealed an association between baseline gut microbiota and pathophysiology and that responders had a different gut microbiota composition. Genomic analyses confirmed that responders had a higher abundance of a Bacteroides-encoded transcriptional regulator required for the conversion of the inactive precursor to bioactive sulforaphane. The abundance of this gene operon correlated with sulforaphane serum concentration. These findings suggest a combined influence of host pathophysiology and gut microbiota on metabolic treatment response, and exploratory analyses need to be confirmed in future trials. ClinicalTrials.gov registration: NCT03763240 .
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Affiliation(s)
- Chinmay Dwibedi
- Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Clinical Microbiology and Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden
| | - Annika S Axelsson
- Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Birgitta Abrahamsson
- Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Jed W Fahey
- Departments of Medicine, Pharmacology and Molecular Sciences, and Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA
| | - Olof Asplund
- Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Malmö, Sweden
| | - Ola Hansson
- Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Malmö, Sweden
- Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland
| | - Emma Ahlqvist
- Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Malmö, Sweden
| | - Valentina Tremaroli
- The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Fredrik Bäckhed
- The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Region Västra Götaland, Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Anders H Rosengren
- Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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Krogstad KC, Vlietstra RJ, Pursley JR, Grilli E, Bradford BJ. On-farm supplementation of rumen-protected niacin: A randomized clinical trial. J Dairy Sci 2025; 108:968-979. [PMID: 39694252 DOI: 10.3168/jds.2024-25489] [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: 07/24/2024] [Accepted: 09/30/2024] [Indexed: 12/20/2024]
Abstract
B vitamins, including niacin (vitamin B3), are synthesized by rumen microbes, but supplementation may provide additional benefits for ruminant health and productivity. Supplementing rumen-protected niacin (RPN) during the transition period can reduce lipolysis after calving and, consequently, may improve health and fertility of dairy cattle later in lactation. Our objective was to determine if supplementing RPN during the first 21 DIM would improve the health of dairy cows on a commercial dairy farm. We hypothesized that RPN would reduce mastitis, improve fertility, and reduce risk of leaving the herd during lactation. Holstein cows were blocked by parity and projected calving date, with treatments randomly assigned to cows within each block. Cows received RPN (n = 481; 26 g/d) through a supplement dispenser in the automated milk systems (AMS) in addition to their robot pellet, or the robot pellet only (CON; n = 593). Treatments were applied for the first 21 DIM, and cows were followed for the rest of their lactation. Milk yield, milk components (wk 1-3 of lactation), pre- and postpartum BCS, health records, and reproductive records were collected. Blood was collected from a random subset of 99 cows at 3 DIM and 97 cows at 10 DIM to assess plasma concentrations of niacin, metabolic biomarkers, and biomarkers of inflammatory status. Culling, proportion of cows pregnant, and mastitis risk were analyzed using Cox proportional hazard models. Mastitis incidence was analyzed with a linear mixed model and conception risk was analyzed using a χ2 test. Supplementing RPN increased plasma nicotinamide concentration by 1,740 nM ± 410.0 nM (SE; 50% increase), but it did not affect plasma nicotinic acid concentrations. Supplementing RPN reduced plasma insulin concentrations at 3 and 10 DIM across all parities. Circulating BHB and free fatty acid concentrations were greater for cows receiving RPN; the effect was greatest in cows in third or greater parity. Plasma haptoglobin was not affected by treatment. Rumen-protected niacin increased milk yield for first- and second-parity cows by wk 9 and 13 of lactation, respectively, and increased milk yield in those groups was sustained for the rest of lactation, resulting in 658 ± 259.4 kg and 675 ± 308.9 kg more milk for RPN-supplemented first- and second-parity cows. The risk of leaving the herd, mastitis incidence, and probability of pregnancy were not affected by RPN. Inquiries into the effects of RPN supplementation and its timing on metabolism are necessary to understand optimal supplementation strategies for RPN in dairy cattle.
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Affiliation(s)
- K C Krogstad
- Department of Animal Science, Michigan State University, East Lansing, MI 48824; Department of Animal Science, The Ohio State University, Wooster, OH 44691.
| | - R J Vlietstra
- West Michigan Veterinary Service, Coopersville, MI 49404
| | - J R Pursley
- Department of Animal Science, Michigan State University, East Lansing, MI 48824
| | - E Grilli
- Department of Veterinary Medical Sciences, University of Bologna: Bologna, 40126 Emilia-Romagna, Italy; Vetagro Inc., Chicago, IL 60605
| | - B J Bradford
- Department of Animal Science, Michigan State University, East Lansing, MI 48824.
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Cabulong RB, Kafle SR, Singh A, Sharma M, Kim BS. Biological production of nicotinamide mononucleotide: a review. Crit Rev Biotechnol 2024:1-18. [PMID: 39675885 DOI: 10.1080/07388551.2024.2433993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 07/30/2024] [Accepted: 10/27/2024] [Indexed: 12/17/2024]
Abstract
Nicotinamide mononucleotide (NMN) presents significant therapeutic potential against aging-related conditions, such as Alzheimer's disease, due to its consistent and strong pharmacological effects. Aside from its anti-aging effect, NMN is also an emerging noncanonical cofactor for orthogonal metabolic pathways in the field of biomanufacturing. This has significant advantages in the field of metabolic engineering, allowing cells to produce unnatural chemicals without disrupting the natural cellular processes. NMN is produced through both the chemical and biological methods, with the latter being more environmentally sustainable. The primary biological production pathway centers on the enzyme nicotinamide phosphoribosyltransferase, which transforms nicotinamide and phosphoribosyl pyrophosphate to NMN. Efforts to increase NMN production have been explored in microorganisms, such as: Escherichia coli, Bacillus subtilis, and yeast, serving as biocatalysts, by rewiring their metabolic processes. Although most researchers are focusing on genetically and metabolically manipulating microorganisms to act as biocatalysts, a growing number of studies on cell-free synthesis are emerging as a promising strategy for producing NMN. This review explores the different biological production techniques of NMN employing microorganisms. This article, in particular, is essential to those who are working on NMN production using microbial strain engineering and cell-free systems.
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Affiliation(s)
- Rhudith B Cabulong
- Department of Chemical Engineering, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
| | - Saroj Raj Kafle
- Department of Chemical Engineering, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
| | - Anju Singh
- Department of Chemical Engineering, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
| | - Mukesh Sharma
- Department of Chemical Engineering, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
| | - Beom Soo Kim
- Department of Chemical Engineering, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
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Zhou J, Han J. Association of niacin intake and metabolic dysfunction-associated steatotic liver disease: findings from National Health and Nutrition Examination Survey. BMC Public Health 2024; 24:2742. [PMID: 39379884 PMCID: PMC11462762 DOI: 10.1186/s12889-024-20161-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 09/23/2024] [Indexed: 10/10/2024] Open
Abstract
AIM This study aims to explore the relationship between niacin intake and the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) within a large, multi-ethnic cohort. METHODS A total of 2946 participants from the National Health and Nutrition Examination Survey (NHANES) were carefully selected based on strict inclusion and exclusion criteria. Participants meeting the eligibility criteria underwent two dietary recall interviews, and niacin intake was calculated using the USDA's Food and Nutrient Database for Dietary Studies (FNDDS). Liver steatosis was diagnosed using a Controlled Attenuation Parameter (CAP) of 248 dB/m, and MASLD diagnosis was based on metabolic indicators. Weighted multivariate logistic regression was utilized to analyze the correlation between niacin intake and MASLD prevalence, with potential nonlinear relationships explored through restricted cubic spline (RCS) regression. RESULTS Analysis of baseline data revealed that MASLD patients had lower niacin intake levels and poorer metabolic biomarker profiles. Both RCS analysis and multivariate logistic regression indicated a U-shaped association between niacin intake and MASLD prevalence. Specifically, there was a non-linear dose-response relationship, with the odds of MASLD gradually decreasing with increasing niacin intake until reaching a threshold of 23.6 mg, beyond which the odds of MASLD began to increase. CONCLUSION This study confirms a U-shaped nonlinear relationship between niacin intake and MASLD prevalence within the diverse American population.
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Affiliation(s)
- Jing Zhou
- Department of Infectious Diseases, Affiliated Wuxi Fifth Hospital of Jiangnan University, The Fifth People's Hospital of Wuxi, Wuxi, 214065, China
| | - Jun Han
- Department of Infectious Diseases, Affiliated Wuxi Fifth Hospital of Jiangnan University, The Fifth People's Hospital of Wuxi, Wuxi, 214065, China.
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Zakerska-Banaszak O, Zuraszek-Szymanska J, Eder P, Ladziak K, Slomski R, Skrzypczak-Zielinska M. The Role of Host Genetics and Intestinal Microbiota and Metabolome as a New Insight into IBD Pathogenesis. Int J Mol Sci 2024; 25:9589. [PMID: 39273536 PMCID: PMC11394875 DOI: 10.3390/ijms25179589] [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: 07/12/2024] [Revised: 08/30/2024] [Accepted: 09/02/2024] [Indexed: 09/15/2024] Open
Abstract
Inflammatory bowel disease (IBD) is an incurable, chronic disorder of the gastrointestinal tract whose incidence increases every year. Scientific research constantly delivers new information about the disease and its multivariate, complex etiology. Nevertheless, full discovery and understanding of the complete mechanism of IBD pathogenesis still pose a significant challenge to today's science. Recent studies have unanimously confirmed the association of gut microbial dysbiosis with IBD and its contribution to the regulation of the inflammatory process. It transpires that the altered composition of pathogenic and commensal bacteria is not only characteristic of disturbed intestinal homeostasis in IBD, but also of viruses, parasites, and fungi, which are active in the intestine. The crucial function of the microbial metabolome in the human body is altered, which causes a wide range of effects on the host, thus providing a basis for the disease. On the other hand, human genomic and functional research has revealed more loci that play an essential role in gut homeostasis regulation, the immune response, and intestinal epithelial function. This review aims to organize and summarize the currently available knowledge concerning the role and interaction of crucial factors associated with IBD pathogenesis, notably, host genetic composition, intestinal microbiota and metabolome, and immune regulation.
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Affiliation(s)
| | | | - Piotr Eder
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland
| | - Karolina Ladziak
- Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland
| | - Ryszard Slomski
- Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland
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Dai C, Li W, Zhang C, Shen X, Wan Z, Deng X, Liu F. Microencapsule delivery systems of functional substances for precision nutrition. ADVANCES IN FOOD AND NUTRITION RESEARCH 2024; 112:199-255. [PMID: 39218503 DOI: 10.1016/bs.afnr.2024.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Microencapsulation, a typical core-shell structure technology, encapsulates functional active ingredients for protection, controlled release, and targeted delivery. In precise nutrition, the focus is on utilizing microcapsule delivery systems for personalized dietary supplements and disease intervention. This chapter outlines the morphological structure of microcapsules, common wall materials, and preparation techniques. It discusses the characteristics of different hydrophilic and lipophilic functional factors and their function as dietary supplements. The role of microencapsulation on the controlled release, odor masking, and enhanced bioavailability of functional factors is explored. Additionally, the application of microcapsule delivery systems in nutritional interventions for diseases like inflammatory bowel disease, alcoholic/fatty liver disease, diabetes, and cancer is introduced in detail. Lastly, the chapter proposes the future developments of anticipation in responsive wall materials for precise nutrition interventions, including both challenges and opportunities.
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Affiliation(s)
- Chenlin Dai
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, P.R. China
| | - Wenhan Li
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, P.R. China
| | - Chairui Zhang
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, P.R. China
| | - Xuelian Shen
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, P.R. China
| | - Ziyan Wan
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, P.R. China
| | - Xiaofan Deng
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, P.R. China
| | - Fuguo Liu
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, P.R. China.
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Marinos G, Hamerich IK, Debray R, Obeng N, Petersen C, Taubenheim J, Zimmermann J, Blackburn D, Samuel BS, Dierking K, Franke A, Laudes M, Waschina S, Schulenburg H, Kaleta C. Metabolic model predictions enable targeted microbiome manipulation through precision prebiotics. Microbiol Spectr 2024; 12:e0114423. [PMID: 38230938 PMCID: PMC10846184 DOI: 10.1128/spectrum.01144-23] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 12/13/2023] [Indexed: 01/18/2024] Open
Abstract
While numerous health-beneficial interactions between host and microbiota have been identified, there is still a lack of targeted approaches for modulating these interactions. Thus, we here identify precision prebiotics that specifically modulate the abundance of a microbiome member species of interest. In the first step, we show that defining precision prebiotics by compounds that are only taken up by the target species but no other species in a community is usually not possible due to overlapping metabolic niches. Subsequently, we use metabolic modeling to identify precision prebiotics for a two-member Caenorhabditis elegans microbiome community comprising the immune-protective target species Pseudomonas lurida MYb11 and the persistent colonizer Ochrobactrum vermis MYb71. We experimentally confirm four of the predicted precision prebiotics, L-serine, L-threonine, D-mannitol, and γ-aminobutyric acid, to specifically increase the abundance of MYb11. L-serine was further assessed in vivo, leading to an increase in MYb11 abundance also in the worm host. Overall, our findings demonstrate that metabolic modeling is an effective tool for the design of precision prebiotics as an important cornerstone for future microbiome-targeted therapies.IMPORTANCEWhile various mechanisms through which the microbiome influences disease processes in the host have been identified, there are still only few approaches that allow for targeted manipulation of microbiome composition as a first step toward microbiome-based therapies. Here, we propose the concept of precision prebiotics that allow to boost the abundance of already resident health-beneficial microbial species in a microbiome. We present a constraint-based modeling pipeline to predict precision prebiotics for a minimal microbial community in the worm Caenorhabditis elegans comprising the host-beneficial Pseudomonas lurida MYb11 and the persistent colonizer Ochrobactrum vermis MYb71 with the aim to boost the growth of MYb11. Experimentally testing four of the predicted precision prebiotics, we confirm that they are specifically able to increase the abundance of MYb11 in vitro and in vivo. These results demonstrate that constraint-based modeling could be an important tool for the development of targeted microbiome-based therapies against human diseases.
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Affiliation(s)
- Georgios Marinos
- Research Group Medical Systems Biology, University Hospital Schleswig-Holstein Campus Kiel, Kiel University, Kiel, Schleswig-Holstein, Germany
| | - Inga K. Hamerich
- Research Group Evolutionary Ecology and Genetics, Zoological Institute, Kiel University, Kiel, Schleswig-Holstein, Germany
| | - Reena Debray
- Department of Integrative Biology, University of California, Berkeley, California, USA
| | - Nancy Obeng
- Research Group Evolutionary Ecology and Genetics, Zoological Institute, Kiel University, Kiel, Schleswig-Holstein, Germany
| | - Carola Petersen
- Research Group Evolutionary Ecology and Genetics, Zoological Institute, Kiel University, Kiel, Schleswig-Holstein, Germany
| | - Jan Taubenheim
- Research Group Medical Systems Biology, University Hospital Schleswig-Holstein Campus Kiel, Kiel University, Kiel, Schleswig-Holstein, Germany
| | - Johannes Zimmermann
- Research Group Medical Systems Biology, University Hospital Schleswig-Holstein Campus Kiel, Kiel University, Kiel, Schleswig-Holstein, Germany
- Max-Planck Institute for Evolutionary Biology, Ploen, Schleswig-Holstein, Germany
| | - Dana Blackburn
- Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, USA
| | - Buck S. Samuel
- Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, USA
| | - Katja Dierking
- Research Group Evolutionary Ecology and Genetics, Zoological Institute, Kiel University, Kiel, Schleswig-Holstein, Germany
| | - Andre Franke
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Schleswig-Holstein, Germany
| | - Matthias Laudes
- Institute of Diabetes and Clinical Metabolic Research, University Hospital Schleswig-Holstein Campus Kiel, Kiel, Schleswig-Holstein, Germany
| | - Silvio Waschina
- Nutriinformatics, Institute for Human Nutrition and Food Science, Kiel University, Kiel, Schleswig-Holstein, Germany
| | - Hinrich Schulenburg
- Research Group Evolutionary Ecology and Genetics, Zoological Institute, Kiel University, Kiel, Schleswig-Holstein, Germany
- Max-Planck Institute for Evolutionary Biology, Ploen, Schleswig-Holstein, Germany
| | - Christoph Kaleta
- Research Group Medical Systems Biology, University Hospital Schleswig-Holstein Campus Kiel, Kiel University, Kiel, Schleswig-Holstein, Germany
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12
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Bedani R, Cucick ACC, Albuquerque MACD, LeBlanc JG, Saad SMI. B-Group Vitamins as Potential Prebiotic Candidates: Their Effects on the Human Gut Microbiome. J Nutr 2024; 154:341-353. [PMID: 38176457 DOI: 10.1016/j.tjnut.2023.12.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 12/18/2023] [Accepted: 12/22/2023] [Indexed: 01/06/2024] Open
Abstract
In recent years, thousands of studies have demonstrated the importance of the gut microbiome for human health and its relationship with certain diseases. The search for new gut microbiome modulators has thus become an objective to beneficially alter the gut microbiome composition and/or metabolic activity, which may modify intestinal physiology. Growing evidence has shown that B-group vitamins might be considered as potential candidates as gut microbiome modulators. However, the relationship between the B-group vitamins and the gut microbiome remains largely unexplored. Studies have suggested that non-absorbed B-group vitamins administered orally can reach the distal intestine or even the colon where these vitamins may have potential health benefits for the host. Clinical trials supporting this effect are still limited. In this review, we discuss evidence regarding the modulatory effects of B-group vitamins on the gut microbiome with a focus on their potential role as prebiotic candidates.
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Affiliation(s)
- Raquel Bedani
- Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil; Food Research Center, University of São Paulo, São Paulo, São Paulo, Brazil.
| | - Ana Clara Candelaria Cucick
- Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil; Food Research Center, University of São Paulo, São Paulo, São Paulo, Brazil
| | - Marcela Albuquerque Cavalcanti de Albuquerque
- Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil; Food Research Center, University of São Paulo, São Paulo, São Paulo, Brazil
| | | | - Susana Marta Isay Saad
- Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil; Food Research Center, University of São Paulo, São Paulo, São Paulo, Brazil
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13
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Yang Z, Bao L, Song W, Zhao X, Liang H, Yu M, Qu M. Nicotinic acid changes rumen fermentation and apparent nutrient digestibility by regulating rumen microbiota in Xiangzhong black cattle. Anim Biosci 2024; 37:240-252. [PMID: 37905319 PMCID: PMC10766483 DOI: 10.5713/ab.23.0149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 06/25/2023] [Accepted: 09/06/2023] [Indexed: 11/02/2023] Open
Abstract
OBJECTIVE The aim of this study was to investigate the impact of dietary nicotinic acid (NA) on apparent nutrient digestibility, rumen fermentation, and rumen microbiota in uncastrated Xiangzhong black cattle. METHODS Twenty-one uncastrated Xiangzhong black cattle (385.08±15.20 kg) aged 1.5 years were randomly assigned to the control group (CL, 0 mg/kg NA in concentrate diet), NA1 group (800 mg/kg NA in concentrate diet) and NA2 group (1,200 mg/kg NA in concentrate diet). All animals were fed a 60% concentrate diet and 40% dried rice straw for a 120-day feeding experiment. RESULTS Supplemental NA not only enhanced the apparent nutrient digestibility of acid detergent fiber (p<0.01), but also elevated the rumen acetate and total volatile fatty acid concentrations (p<0.05). 16S rRNA gene sequencing analysis of rumen microbiota revealed that dietary NA changed the diversity of rumen microbiota (p<0.05) and the abundance of bacterial taxa in the rumen. The relative abundances of eight Erysipelotrichales taxa, five Ruminococcaceae taxa, and five Sphaerochaetales taxa were decreased by dietary NA (p< 0.05). However, the relative abundances of two taxa belonging to Roseburia faecis were increased by supplemental 800 mg/kg NA, and the abundances of seven Prevotella taxa, three Paraprevotellaceae taxa, three Bifidobacteriaceae taxa, and two operational taxonomic units annotated to Fibrobacter succinogenes were increased by 1,200 mg/kg NA in diets. Furthermore, the correlation analysis found significant correlations between the concentrations of volatile fatty acids in the rumen and the abundances of bacterial taxa, especially Prevotella. CONCLUSION The results from this study suggest that dietary NA plays an important role in regulating apparent digestibility of acid detergent fiber, acetate, total volatile fatty acid concentrations, and the composition of rumen microbiota.
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Affiliation(s)
- Zhuqing Yang
- College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045,
China
| | - Linbin Bao
- Animal Husbandry and Veterinary Bureau of Guangchang County, Fuzhou, Jiangxi, 344900,
China
| | - Wanming Song
- College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045,
China
| | - Xianghui Zhao
- Jiangxi Provincial Key Laboratory for Animal Nutrition/Engineering Research Center of Feed Development, Jiangxi Agricultural University, Nanchang, 330045,
China
| | - Huan Liang
- Jiangxi Provincial Key Laboratory for Animal Nutrition/Engineering Research Center of Feed Development, Jiangxi Agricultural University, Nanchang, 330045,
China
| | - Mingjin Yu
- College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045,
China
| | - Mingren Qu
- Jiangxi Provincial Key Laboratory for Animal Nutrition/Engineering Research Center of Feed Development, Jiangxi Agricultural University, Nanchang, 330045,
China
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14
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Starke S, Harris DMM, Zimmermann J, Schuchardt S, Oumari M, Frank D, Bang C, Rosenstiel P, Schreiber S, Frey N, Franke A, Aden K, Waschina S. Amino acid auxotrophies in human gut bacteria are linked to higher microbiome diversity and long-term stability. THE ISME JOURNAL 2023; 17:2370-2380. [PMID: 37891427 PMCID: PMC10689445 DOI: 10.1038/s41396-023-01537-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 10/06/2023] [Accepted: 10/09/2023] [Indexed: 10/29/2023]
Abstract
Amino acid auxotrophies are prevalent among bacteria. They can govern ecological dynamics in microbial communities and indicate metabolic cross-feeding interactions among coexisting genotypes. Despite the ecological importance of auxotrophies, their distribution and impact on the diversity and function of the human gut microbiome remain poorly understood. This study performed the first systematic analysis of the distribution of amino acid auxotrophies in the human gut microbiome using a combined metabolomic, metagenomic, and metabolic modeling approach. Results showed that amino acid auxotrophies are ubiquitous in the colon microbiome, with tryptophan auxotrophy being the most common. Auxotrophy frequencies were higher for those amino acids that are also essential to the human host. Moreover, a higher overall abundance of auxotrophies was associated with greater microbiome diversity and stability, and the distribution of auxotrophs was found to be related to the human host's metabolome, including trimethylamine oxide, small aromatic acids, and secondary bile acids. Thus, our results suggest that amino acid auxotrophies are important factors contributing to microbiome ecology and host-microbiome metabolic interactions.
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Affiliation(s)
- Svenja Starke
- Institute of Human Nutrition and Food Science, Nutriinformatics, Kiel University, Kiel, Germany
| | - Danielle M M Harris
- Institute of Human Nutrition and Food Science, Nutriinformatics, Kiel University, Kiel, Germany
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
| | - Johannes Zimmermann
- Zoological Institute, Research Group Evolutionary Ecology and Genetics, Kiel University, Kiel, Germany
- Max Planck Institute for Evolutionary Biology, Plön, Germany
| | - Sven Schuchardt
- Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hanover, Germany
| | - Mhmd Oumari
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
| | - Derk Frank
- Department of Internal Medicine III, University Medical Center Schleswig-Holstein, Kiel, Germany
- German Centre for Cardiovascular Research (DZHK), Partner site Hamburg, Kiel, Lübeck, Germany
| | - Corinna Bang
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
| | - Philip Rosenstiel
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
| | - Stefan Schreiber
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
- Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Norbert Frey
- Department of Internal Medicine III, University Medical Center Schleswig-Holstein, Kiel, Germany
- German Centre for Cardiovascular Research (DZHK), Partner site Hamburg, Kiel, Lübeck, Germany
- Department of Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany
| | - Andre Franke
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
| | - Konrad Aden
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.
- Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany.
| | - Silvio Waschina
- Institute of Human Nutrition and Food Science, Nutriinformatics, Kiel University, Kiel, Germany.
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Abstract
Niacin (vitamin B3) is an essential nutrient that treats pellagra, and prior to the advent of statins, niacin was commonly used to counter dyslipidemia. Recent evidence has posited niacin as a promising therapeutic for several neurological disorders. In this review, we discuss the biochemistry of niacin, including its homeostatic roles in NAD+ supplementation and metabolism. Niacin also has roles outside of metabolism, largely through engaging hydroxycarboxylic acid receptor 2 (Hcar2). These receptor-mediated activities of niacin include regulation of immune responses, phagocytosis of myelin debris after demyelination or of amyloid beta in models of Alzheimer's disease, and cholesterol efflux from cells. We describe the neurological disorders in which niacin has been investigated or has been proposed as a candidate medication. These are multiple sclerosis, Alzheimer's disease, Parkinson's disease, glioblastoma and amyotrophic lateral sclerosis. Finally, we explore the proposed mechanisms through which niacin may ameliorate neuropathology. While several questions remain, the prospect of niacin as a therapeutic to alleviate neurological impairment is promising.
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Affiliation(s)
- Emily Wuerch
- Hotchkiss Brain Institute, 3330 Hospital Drive NW, Calgary, AB, Canada
- Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
| | - Gloria Roldan Urgoiti
- Hotchkiss Brain Institute, 3330 Hospital Drive NW, Calgary, AB, Canada
- Arnie Charbonneau Cancer Institute, Calgary, AB, Canada
- Department of Oncology, University of Calgary, Calgary, AB, Canada
| | - V Wee Yong
- Hotchkiss Brain Institute, 3330 Hospital Drive NW, Calgary, AB, Canada.
- Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
- Department of Oncology, University of Calgary, Calgary, AB, Canada.
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16
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Ahmed AA, Otten AT, Gareb B, Huijmans JE, Eissens AC, Rehman A, Dijkstra G, Kosterink JGW, Frijlink HW, Schellekens RCA. Capsules with Ileocolonic-Targeted Release of Vitamin B 2, B 3, and C (ColoVit) Intended for Optimization of Gut Health: Development and Validation of the Production Process. Pharmaceutics 2023; 15:1354. [PMID: 37242596 PMCID: PMC10223462 DOI: 10.3390/pharmaceutics15051354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 04/21/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023] Open
Abstract
The ileocolonic-targeted delivery of vitamins can establish beneficial alterations in gut microbial composition. Here, we describe the development of capsules containing riboflavin, nicotinic acid, and ascorbic acid covered with a pH-sensitive coating (ColoVit) to establish site-specific release in the ileocolon. Ingredient properties (particle size distribution, morphology) relevant for formulation and product quality were determined. Capsule content and the in vitro release behaviour were determined using a HPLC-method. Uncoated and coated validation batches were produced. Release characteristics were evaluated using a gastro-intestinal simulation system. All capsules met the required specifications. The contents of the ingredients were in the 90.0-120.0% range, and uniformity requirements were met. In the dissolution test a lag-time in drug release of 277-283 min was found, which meets requirements for ileocolonic release. The release itself is immediate as shown by dissolution of the vitamins of more than 75% in 1 h. The production process of the ColoVit formulation was validated and reproducible, it was shown that the vitamin blend was stable during the production process and in the finished coated product. The ColoVit is intended as an innovative treatment approach for beneficial microbiome modulation and optimization of gut health.
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Affiliation(s)
- Aisha A. Ahmed
- Apotheek A15, 4207 HT Gorinchem, The Netherlands; (A.A.A.)
| | - Antonius T. Otten
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
| | - Bahez Gareb
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
| | | | - Anko C. Eissens
- Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands
| | | | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
| | - Jos G. W. Kosterink
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
- Department of Pharmaco Therapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands
| | - Henderik W. Frijlink
- Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands
| | - Reinout C. A. Schellekens
- Apotheek A15, 4207 HT Gorinchem, The Netherlands; (A.A.A.)
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
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17
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Rehman A, Pham V, Seifert N, Richard N, Sybesma W, Steinert RE. The Polyunsaturated Fatty Acids Eicosapentaenoic Acid and Docosahexaenoic Acid, and Vitamin K 1 Modulate the Gut Microbiome: A Study Using an In Vitro Shime Model. J Diet Suppl 2023; 21:135-153. [PMID: 37078491 DOI: 10.1080/19390211.2023.2198007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/21/2023]
Abstract
Omega-3 polyunsaturated fatty acids (PUFAs) and vitamins exert multiple beneficial effects on host health, some of which may be mediated through the gut microbiome. We investigated the prebiotic potential of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and lipid-soluble phylloquinone (vitamin K1), each at 0.2x, 1x and 5x using the simulator of the human intestinal microbial ecosystem (SHIME®) to exclude in vivo systemic effects and host-microbe interactions.Microbial community composition and, diversity [shotgun metagenomic sequencing] and microbial activity [pH, gas pressure, and production of short-chain fatty acids (SCFAs)] were measured over a period of 48 h. Fermentations supernatants were used to investigate the effect on gut barrier integrity using a Caco-2/goblet cell co-culture model.We found that EPA, DHA and vitamin K1 increased alpha-diversity at 24 h when compared with control. Moreover, there was an effect on beta-diversity with changes in gut microbial composition, such as an increase in the Firmicutes/Bacteroidetes (F/B) ratio and a consistent increase in Veillonella and Dialister abundances with all treatments. DHA, EPA, and vitamin K1 also modulated metabolic activity of the gut microbiome by increasing total SCFAs which was related mainly to an increase in propionate (highest with EPA and vitamin K1 at 0.2x). Finally, we found that EPA and DHA increased gut barrier integrity with DHA at 1x and EPA at 5x (p < 0.05, respectively). In conclusion, our in vitro data further establish a role of PUFAs and vitamin K to modulate the gut microbiome with effects on the production of SCFAs and barrier integrity.
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Affiliation(s)
- Ateequr Rehman
- Human Nutrition and Health, DSM Nutritional Products Ltd, Basel, Switzerland
| | - Van Pham
- Human Nutrition and Health, DSM Nutritional Products Ltd, Basel, Switzerland
| | - Nicole Seifert
- Human Nutrition and Health, DSM Nutritional Products Ltd, Basel, Switzerland
| | - Nathalie Richard
- Human Nutrition and Health, DSM Nutritional Products Ltd, Basel, Switzerland
| | - Wilbert Sybesma
- Human Nutrition and Health, DSM Nutritional Products Ltd, Basel, Switzerland
| | - Robert E Steinert
- Human Nutrition and Health, DSM Nutritional Products Ltd, Basel, Switzerland
- Department of Surgery, Division of Visceral and Transplantation Surgery, University Hospital Zurich, Zurich, Switzerland
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18
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He D, Fu S, Ye B, Wang H, He Y, Li Z, Li J, Gao X, Liu D. Activation of HCA2 regulates microglial responses to alleviate neurodegeneration in LPS-induced in vivo and in vitro models. J Neuroinflammation 2023; 20:86. [PMID: 36991440 PMCID: PMC10053461 DOI: 10.1186/s12974-023-02762-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 03/10/2023] [Indexed: 03/31/2023] Open
Abstract
BACKGROUND Previous studies have shown a close association between an altered immune system and Parkinson's disease (PD). Neuroinflammation inhibition may be an effective measure to prevent PD. Recently, numerous reports have highlighted the potential of hydroxy-carboxylic acid receptor 2 (HCA2) in inflammation-related diseases. Notably, the role of HCA2 in neurodegenerative diseases is also becoming more widely known. However, its role and exact mechanism in PD remain to be investigated. Nicotinic acid (NA) is one of the crucial ligands of HCA2, activating it. Based on such findings, this study aimed to examine the effect of HCA2 on neuroinflammation and the role of NA-activated HCA2 in PD and its underlying mechanisms. METHODS For in vivo studies, 10-week-old male C57BL/6 and HCA2-/- mice were injected with LPS in the substantia nigra (SN) to construct a PD model. The motor behavior of mice was detected using open field, pole-climbing and rotor experiment. The damage to the mice's dopaminergic neurons was detected using immunohistochemical staining and western blotting methods. In vitro, inflammatory mediators (IL-6, TNF-α, iNOS and COX-2) and anti-inflammatory factors (Arg-1, Ym-1, CD206 and IL-10) were detected using RT-PCR, ELISA and immunofluorescence. Inflammatory pathways (AKT, PPARγ and NF-κB) were delineated by RT-PCR and western blotting. Neuronal damage was detected using CCK8, LDH, and flow cytometry assays. RESULTS HCA2-/- increases mice susceptibility to dopaminergic neuronal injury, motor deficits, and inflammatory responses. Mechanistically, HCA2 activation in microglia promotes anti-inflammatory microglia and inhibits pro-inflammatory microglia by activating AKT/PPARγ and inhibiting NF-κB signaling pathways. Further, HCA2 activation in microglia attenuates microglial activation-mediated neuronal injury. Moreover, nicotinic acid (NA), a specific agonist of HCA2, alleviated dopaminergic neuronal injury and motor deficits in PD mice by activating HCA2 in microglia in vivo. CONCLUSIONS Niacin receptor HCA2 modulates microglial phenotype to inhibit neurodegeneration in LPS-induced in vivo and in vitro models.
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Affiliation(s)
- Dewei He
- College of Animal Science, Jilin University, Changchun, China
| | - Shoupeng Fu
- College of Veterinary Medicine, Jilin University, Changchun, China
| | - Bojian Ye
- College of Veterinary Medicine, Jilin University, Changchun, China
| | - Hefei Wang
- College of Veterinary Medicine, Jilin University, Changchun, China
| | - Yuan He
- College of Veterinary Medicine, Jilin University, Changchun, China
| | - Zhe Li
- College of Veterinary Medicine, Jilin University, Changchun, China
| | - Jie Li
- College of Animal Science, Jilin University, Changchun, China
| | - Xiyu Gao
- College of Animal Science, Jilin University, Changchun, China
| | - Dianfeng Liu
- College of Animal Science, Jilin University, Changchun, China.
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19
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Costa CJ, Cohen MW, Goldberg DC, Mellado W, Willis DE. Nicotinamide Riboside Improves Enteric Neuropathy in Streptozocin-Induced Diabetic Rats Through Myenteric Plexus Neuroprotection. Dig Dis Sci 2023:10.1007/s10620-023-07913-5. [PMID: 36920665 DOI: 10.1007/s10620-023-07913-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 03/03/2023] [Indexed: 03/16/2023]
Abstract
BACKGROUND Diabetes Mellitus causes a systemic oxidative stress due in part to the hyperglycemia and the reactive oxygen species generated. Up to 75% of diabetic patients present with an autonomic neuropathy affecting the Enteric Nervous System. Deficits in the human population are chronic dysmotilities with either increased (i.e., constipation) or decreased (i.e., diarrhea) total gastrointestinal transit times. These are recapitulated in the streptozocin-induced diabetic rat, which is a model of Type I Diabetes Mellitus. AIMS Examine the effects that a precursor of nicotinamide adenosine dinucleotide (NAD), nicotinamide riboside (NR), had on the development of dysmotility in induced diabetic rats and if fecal microbiota transplant (FMT) could produce the same results. MATERIALS AND METHODS Utilizing a 6-week treatment paradigm, NR was administered intraperitoneally every 48 h. Total gastrointestinal transit time was assessed weekly utilizing the carmine red method. Three weeks following hyperglycemic induction, FMT was performed between NR-treated animals and untreated animals. SIGNIFICANT RESULTS There is improvement in overall gastrointestinal transit time with the use of NR. 16S microbiome sequencing demonstrated decreased alpha and beta diversity in induced diabetic rats without change in animals receiving FMT. Improvements in myenteric plexus ganglia density in small and large intestines in diabetic animals treated with NR were seen. CONCLUSIONS NR treatment led to functional improvement in total gastrointestinal transit time in induced diabetic animals. This was associated with neuroprotection in the myenteric plexuses of both small and large intestines of induced diabetic rats. This represents an important first step in showing NR's benefit as a treatment for diabetic enteric neuropathy. Streptozocin-induced diabetic rats have improved transit times and increased myenteric plexus ganglia density when treated with intraperitoneal nicotinamide riboside.
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Affiliation(s)
- Christopher J Costa
- Quinnipiac University Frank H Netter MD School of Medicine, North Haven, CT, USA. .,Burke Neurological Institute, 785 Mamaroneck Ave, White Plains, NY, 10605, USA. .,Graduate Medical Education, Internal Medicine Residency, UConn Health, 263 Farmington Ave, Farmington, CT, 06030-1235, USA.
| | - Melanie W Cohen
- Burke Neurological Institute, 785 Mamaroneck Ave, White Plains, NY, 10605, USA
| | - David C Goldberg
- Burke Neurological Institute, 785 Mamaroneck Ave, White Plains, NY, 10605, USA.,Children's Hospital of Philadelphia, 3501 Civic Center Blvd, Philadelphia, PA, 19104, USA
| | - Wilfredo Mellado
- Burke Neurological Institute, 785 Mamaroneck Ave, White Plains, NY, 10605, USA
| | - Dianna E Willis
- Burke Neurological Institute, 785 Mamaroneck Ave, White Plains, NY, 10605, USA.,Weill Cornell Medicine Feil Family Brain and Mind Research Institute, New York, NY, USA
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Lapatto HA, Kuusela M, Heikkinen A, Muniandy M, van der Kolk BW, Gopalakrishnan S, Pöllänen N, Sandvik M, Schmidt MS, Heinonen S, Saari S, Kuula J, Hakkarainen A, Tampio J, Saarinen T, Taskinen MR, Lundbom N, Groop PH, Tiirola M, Katajisto P, Lehtonen M, Brenner C, Kaprio J, Pekkala S, Ollikainen M, Pietiläinen KH, Pirinen E. Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study. SCIENCE ADVANCES 2023; 9:eadd5163. [PMID: 36638183 PMCID: PMC9839336 DOI: 10.1126/sciadv.add5163] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 12/09/2022] [Indexed: 06/17/2023]
Abstract
Nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide riboside (NR) has emerged as a promising compound to improve obesity-associated mitochondrial dysfunction and metabolic syndrome in mice. However, most short-term clinical trials conducted so far have not reported positive outcomes. Therefore, we aimed to determine whether long-term NR supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twenty body mass index (BMI)-discordant monozygotic twin pairs were supplemented with an escalating dose of NR (250 to 1000 mg/day) for 5 months. NR improved systemic NAD+ metabolism, muscle mitochondrial number, myoblast differentiation, and gut microbiota composition in both cotwins. NR also showed a capacity to modulate epigenetic control of gene expression in muscle and adipose tissue in both cotwins. However, NR did not ameliorate adiposity or metabolic health. Overall, our results suggest that NR acts as a potent modifier of NAD+ metabolism, muscle mitochondrial biogenesis and stem cell function, gut microbiota, and DNA methylation in humans irrespective of BMI.
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Affiliation(s)
- Helena A. K. Lapatto
- Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland
| | - Minna Kuusela
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland
| | - Aino Heikkinen
- Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland
| | - Maheswary Muniandy
- Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland
| | - Birgitta W. van der Kolk
- Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland
| | | | - Noora Pöllänen
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland
| | - Martin Sandvik
- Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland
| | - Mark S. Schmidt
- Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Sini Heinonen
- Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland
| | - Sina Saari
- Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland
| | - Juho Kuula
- Department of Radiology, Medical Imaging Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
- Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland
- Population Health Unit, Finnish Institute for Health and Welfare, Oulu, Finland
| | - Antti Hakkarainen
- Department of Radiology, Medical Imaging Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Janne Tampio
- School of Pharmacy, University of Eastern Finland, Kuopio, Finland
| | - Tuure Saarinen
- Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland
- Abdominal Center, Department of Gastrointestinal Surgery, Helsinki University Hospital, Helsinki, Finland
| | - Marja-Riitta Taskinen
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland
| | - Nina Lundbom
- Department of Radiology, Medical Imaging Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Per-Henrik Groop
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
- Abdominal Center, Nephrology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia
| | - Marja Tiirola
- Department of Environmental and Biological Sciences, University of Jyväskylä, FI-40014 Jyväskylä, Finland
| | - Pekka Katajisto
- Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland
- Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
| | - Marko Lehtonen
- School of Pharmacy, University of Eastern Finland, Kuopio, Finland
| | - Charles Brenner
- Department of Diabetes and Cancer Metabolism, City of Hope National Medical Center, Duarte, CA 91010, USA
| | - Jaakko Kaprio
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland
| | - Satu Pekkala
- Faculty of Sport and Health Sciences, University of Jyväskylä, FI-40014 Jyväskylä, Finland
| | - Miina Ollikainen
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland
- Minerva Foundation Institute for Medical Research, Helsinki, Finland
| | - Kirsi H. Pietiläinen
- Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland
- Abdominal Center, Healthy Weight Hub, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Eija Pirinen
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland
- Research Unit of Biomedicine and Internal Medicine, Faculty of Medicine, University of Oulu, FIN-90220 Oulu, Finland
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21
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Zhao J, Lu W, Huang S, Le Maho Y, Habold C, Zhang Z. Impacts of Dietary Protein and Niacin Deficiency on Reproduction Performance, Body Growth, and Gut Microbiota of Female Hamsters (Tscherskia triton) and Their Offspring. Microbiol Spectr 2022; 10:e0015722. [PMID: 36318010 PMCID: PMC9784777 DOI: 10.1128/spectrum.00157-22] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 10/10/2022] [Indexed: 11/07/2022] Open
Abstract
Food resources are vital for animals to survive, and gut microbiota play an essential role in transferring nutritional materials into functional metabolites for hosts. Although the fact that diet affects host microbiota is well known, its impacts on offspring remain unclear. In this study, we assessed the effects of low-protein and niacin-deficient diets on reproduction performance, body growth, and gut microbiota of greater long-tailed hamsters (Tscherskia triton) under laboratory conditions. We found that maternal low-protein diet (not niacin deficiency) had a significant negative effect on reproduction performance of female hamsters (longer mating latency with males and smaller litter size) and body growth (lower body weight) of both female hamsters and their offspring. Both protein- and niacin-deficient diets showed significant maternal effects on the microbial community in the offspring. A maternal low-protein diet (not niacin deficiency) significantly reduced the abundance of major bacterial taxa producing short-chain fatty acids, increased the abundance of probiotic taxa, and altered microbial function in the offspring. The negative effects of maternal nutritional deficiency on gut microbiota are more pronounced in the protein group than the niacin group and in offspring more than in female hamsters. Our results suggest that a low-protein diet could alter gut microbiota in animals, which may result in negative impacts on their fitness. It is necessary to conduct further analysis to reveal the roles of nutrition, as well as its interaction with gut microbes, in affecting fitness of greater long-tailed hamsters under field conditions. IMPORTANCE Gut microbes are known to be essential for hosts to digest food and absorb nutrients. Currently, it is still unclear how maternal nutrient deficiency affects the fitness of animals by its effect on gut microbes. Here, we evaluated the effects of protein- and niacin-deficient diets on mating behavior, reproduction, body growth, and gut microbiota of both mothers and offspring of the greater long-tailed hamster (Tscherskia triton) under laboratory conditions. We found that a low-protein diet significantly reduced maternal reproduction performance and body growth of both mothers and their offspring. Both protein and niacin deficiencies showed significant maternal effects on the microbial community of the offspring. Our results hint that nutritional deficiency may be a potential factor in causing the observed sustained population decline of the greater long-tailed hamsters due to intensified monoculture in the North China Plain, and this needs further field investigation.
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Affiliation(s)
- Jidong Zhao
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, People’s Republic of China
- Shaanxi Key Laboratory of Qinling Ecological Security, Shaanxi Institute of Zoology, Xi'an, People’s Republic of China
| | - Wei Lu
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, People’s Republic of China
| | - Shuli Huang
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, People’s Republic of China
| | - Yvon Le Maho
- University of Strasbourg, CNRS, IPHC, UMR 7178, Strasbourg, France
- Scientific Centre of Monaco, Monaco Principality, Monaco
| | - Caroline Habold
- University of Strasbourg, CNRS, IPHC, UMR 7178, Strasbourg, France
| | - Zhibin Zhang
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, People’s Republic of China
- CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, People’s Republic of China
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22
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Wan Z, Zheng J, Zhu Z, Sang L, Zhu J, Luo S, Zhao Y, Wang R, Zhang Y, Hao K, Chen L, Du J, Kan J, He H. Intermediate role of gut microbiota in vitamin B nutrition and its influences on human health. Front Nutr 2022; 9:1031502. [PMID: 36583209 PMCID: PMC9792504 DOI: 10.3389/fnut.2022.1031502] [Citation(s) in RCA: 72] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 11/28/2022] [Indexed: 12/14/2022] Open
Abstract
Vitamin B consists of a group of water-soluble micronutrients that are mainly derived from the daily diet. They serve as cofactors, mediating multiple metabolic pathways in humans. As an integrated part of human health, gut microbiota could produce, consume, and even compete for vitamin B with the host. The interplay between gut microbiota and the host might be a crucial factor affecting the absorbing processes of vitamin B. On the other hand, vitamin B supplementation or deficiency might impact the growth of specific bacteria, resulting in changes in the composition and function of gut microbiota. Together, the interplay between vitamin B and gut microbiota might systemically contribute to human health. In this review, we summarized the interactions between vitamin B and gut microbiota and tried to reveal the underlying mechanism so that we can have a better understanding of its role in human health.
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Affiliation(s)
- Zhijie Wan
- Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China
| | | | | | - Lan Sang
- Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China
| | - Jinwei Zhu
- Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China
| | - Shizheng Luo
- Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China
| | - Yixin Zhao
- Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China
| | - Ruirui Wang
- Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China
| | - Yicui Zhang
- Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China
| | - Kun Hao
- Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China
| | - Liang Chen
- Nutrilite Health Institute, Shanghai, China
| | - Jun Du
- Nutrilite Health Institute, Shanghai, China
| | - Juntao Kan
- Nutrilite Health Institute, Shanghai, China
| | - Hua He
- Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China
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23
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Marathe SJ, Snider MA, Flores-Torres AS, Dubin PJ, Samarasinghe AE. Human matters in asthma: Considering the microbiome in pulmonary health. Front Pharmacol 2022; 13:1020133. [PMID: 36532717 PMCID: PMC9755222 DOI: 10.3389/fphar.2022.1020133] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 11/15/2022] [Indexed: 07/25/2023] Open
Abstract
Microbial communities form an important symbiotic ecosystem within humans and have direct effects on health and well-being. Numerous exogenous factors including airborne triggers, diet, and drugs impact these established, but fragile communities across the human lifespan. Crosstalk between the mucosal microbiota and the immune system as well as the gut-lung axis have direct correlations to immune bias that may promote chronic diseases like asthma. Asthma initiation and pathogenesis are multifaceted and complex with input from genetic, epigenetic, and environmental components. In this review, we summarize and discuss the role of the airway microbiome in asthma, and how the environment, diet and therapeutics impact this low biomass community of microorganisms. We also focus this review on the pediatric and Black populations as high-risk groups requiring special attention, emphasizing that the whole patient must be considered during treatment. Although new culture-independent techniques have been developed and are more accessible to researchers, the exact contribution the airway microbiome makes in asthma pathogenesis is not well understood. Understanding how the airway microbiome, as a living entity in the respiratory tract, participates in lung immunity during the development and progression of asthma may lead to critical new treatments for asthma, including population-targeted interventions, or even more effective administration of currently available therapeutics.
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Affiliation(s)
- Sandesh J. Marathe
- Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
- Division of Pulmonology, Allergy-Immunology, and Sleep, Memphis, TN, United States
- Children’s Foundation Research Institute, Le Bonheur Children’s Hospital, Memphis, TN, United States
| | - Mark A. Snider
- Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
- Division of Emergency Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Armando S. Flores-Torres
- Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
- Children’s Foundation Research Institute, Le Bonheur Children’s Hospital, Memphis, TN, United States
| | - Patricia J. Dubin
- Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
- Division of Pulmonology, Allergy-Immunology, and Sleep, Memphis, TN, United States
| | - Amali E. Samarasinghe
- Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
- Division of Pulmonology, Allergy-Immunology, and Sleep, Memphis, TN, United States
- Children’s Foundation Research Institute, Le Bonheur Children’s Hospital, Memphis, TN, United States
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24
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Frąk M, Grenda A, Krawczyk P, Milanowski J, Kalinka E. Interactions between Dietary Micronutrients, Composition of the Microbiome and Efficacy of Immunotherapy in Cancer Patients. Cancers (Basel) 2022; 14:5577. [PMID: 36428677 PMCID: PMC9688200 DOI: 10.3390/cancers14225577] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 11/07/2022] [Accepted: 11/11/2022] [Indexed: 11/16/2022] Open
Abstract
The effectiveness of immunotherapy in cancer patients depends on the activity of the host's immune system. The intestinal microbiome is a proven immune system modulator, which plays an important role in the development of many cancers and may affect the effectiveness of anti-cancer therapy. The richness of certain bacteria in the gut microbiome (e.g., Bifidobacterium spp., Akkermanisa muciniphila and Enterococcus hire) improves anti-tumor specific immunity and the response to anti-PD-1 or anti-PD-L1 immunotherapy by activating antigen-presenting cells and cytotoxic T cells within the tumor. Moreover, micronutrients affect directly the activities of the immune system or regulate their function by influencing the composition of the microbiome. Therefore, micronutrients can significantly influence the effectiveness of immunotherapy and the development of immunorelated adverse events. In this review, we describe the relationship between the supply of microelements and the abundance of various bacteria in the intestinal microbiome and the effectiveness of immunotherapy in cancer patients. We also point to the function of the immune system in the case of shifts in the composition of the microbiome and disturbances in the supply of microelements. This may in the future become a therapeutic target supporting the effects of immunotherapy in cancer patients.
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Affiliation(s)
- Małgorzata Frąk
- Chair and Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Anna Grenda
- Chair and Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Paweł Krawczyk
- Chair and Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Janusz Milanowski
- Chair and Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Ewa Kalinka
- Department of Oncology, Polish Mother’s Memorial Hospital—Research Institute, 93-338 Lodz, Poland
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25
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Zhan Q, Wang R, Thakur K, Feng JY, Zhu YY, Zhang JG, Wei ZJ. Unveiling of dietary and gut-microbiota derived B vitamins: Metabolism patterns and their synergistic functions in gut-brain homeostasis. Crit Rev Food Sci Nutr 2022; 64:4046-4058. [PMID: 36271691 DOI: 10.1080/10408398.2022.2138263] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Nutrition-gut cross-talk holds a vital position in sustaining intestinal function, and micronutrient metabolism has emerged as the foremost metabolic pathway to preserve gut homeostasis. Among micronutrients, B vitamins have evolved prior to DNA/RNA and are known for their vital roles for major evolutionary transitions in extant organisms. Despite their universal requirement and critical role, not all the three domains of life are endowed with a natural ability for de novo B vitamins synthesis. The human gut microbiome constitutes prototrophs and auxotroph which are entirely dependent on dietary intake and gut microbial production of B vitamins. The syntrophic metabolism involving cross-feeding of B vitamins and community-wide exchange between commensal bacteria elicit important changes in the diversity and composition of the human gut microbiome. Hereto, we discuss the B-vitamins sharing among prototrophic and auxotrophic gut bacteria, their absorption in small intestine and transport in distal gut, functional role in relation to the gut homeostasis and symptoms linked to their deficiency. We also briefly explore their potential involvement as psychobiotics in brain energetic metabolism (kynurenines/tryptophan pathway) for neurological functions and highlight their deficiency related malfunctioning.
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Affiliation(s)
- Qi Zhan
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, People's Republic of China
| | - Rui Wang
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, People's Republic of China
| | - Kiran Thakur
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, People's Republic of China
- Ningxia Key Laboratory for the Development and Application of Microbial Resources in Extreme Environments, School of Biological Science and Engineering, North Minzu University, Yinchuan, People's Republic of China
| | - Jing-Yu Feng
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, People's Republic of China
| | - Yun-Yang Zhu
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, People's Republic of China
| | - Jian-Guo Zhang
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, People's Republic of China
- Ningxia Key Laboratory for the Development and Application of Microbial Resources in Extreme Environments, School of Biological Science and Engineering, North Minzu University, Yinchuan, People's Republic of China
| | - Zhao-Jun Wei
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, People's Republic of China
- Ningxia Key Laboratory for the Development and Application of Microbial Resources in Extreme Environments, School of Biological Science and Engineering, North Minzu University, Yinchuan, People's Republic of China
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26
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Cohort profile: the Food Chain Plus (FoCus) cohort. Eur J Epidemiol 2022; 37:1087-1105. [PMID: 36245062 PMCID: PMC9630232 DOI: 10.1007/s10654-022-00924-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 09/25/2022] [Indexed: 11/16/2022]
Abstract
The Food Chain Plus (FoCus) cohort was launched in 2011 for population-based research related to metabolic inflammation. To characterize this novel pathology in a comprehensive manner, data collection included multiple omics layers such as phenomics, microbiomics, metabolomics, genomics, and metagenomics as well as nutrition profiling, taste perception phenotyping and social network analysis. The cohort was set-up to represent a Northern German population of the Kiel region. Two-step recruitment included the randomised enrolment of participants via residents’ registration offices and via the Obesity Outpatient Centre of the University Medical Center Schleswig–Holstein (UKSH). Hence, both a population- and metabolic inflammation- based cohort was created. In total, 1795 individuals were analysed at baseline. Baseline data collection took place between 2011 and 2014, including 63% females and 37% males with an age range of 18–83 years. The median age of all participants was 52.0 years [IQR: 42.5; 63.0 years] and the median baseline BMI in the study population was 27.7 kg/m2 [IQR: 23.7; 35.9 kg/m2]. In the baseline cohort, 14.1% of participants had type 2 diabetes mellitus, which was more prevalent in the subjects of the metabolic inflammation group (MIG; 31.8%). Follow-up for the assessment of disease progression, as well as the onset of new diseases with changes in subject’s phenotype, diet or lifestyle factors is planned every 5 years. The first follow-up period was finished in 2020 and included 820 subjects.
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27
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B Vitamins and Their Roles in Gut Health. Microorganisms 2022; 10:microorganisms10061168. [PMID: 35744686 PMCID: PMC9227236 DOI: 10.3390/microorganisms10061168] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 06/02/2022] [Accepted: 06/04/2022] [Indexed: 02/04/2023] Open
Abstract
B vitamins act as coenzymes in a myriad of cellular reactions. These include energy production, methyl donor generation, neurotransmitter synthesis, and immune functions. Due to the ubiquitous roles of these vitamins, their deficiencies significantly affect the host’s metabolism. Recently, novel roles of B vitamins in the homeostasis of gut microbial ecology and intestinal health continue to be unravelled. This review focuses on the functional roles and biosynthesis of B vitamins and how these vitamins influence the growth and proliferation of the gut microbiota. We have identified the gut bacteria that can produce vitamins, and their biosynthetic mechanisms are presented. The effects of B vitamin deficiencies on intestinal morphology, inflammation, and its effects on intestinal disorders are also discussed.
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28
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Luo C, Yang C, Wang X, Chen Y, Liu X, Deng H. Nicotinamide reprograms adipose cellular metabolism and increases mitochondrial biogenesis to ameliorate obesity. J Nutr Biochem 2022; 107:109056. [DOI: 10.1016/j.jnutbio.2022.109056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 03/22/2022] [Accepted: 04/06/2022] [Indexed: 11/29/2022]
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29
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HDHL-INTIMIC: A European Knowledge Platform on Food, Diet, Intestinal Microbiomics, and Human Health. Nutrients 2022; 14:nu14091881. [PMID: 35565847 PMCID: PMC9100002 DOI: 10.3390/nu14091881] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/22/2022] [Accepted: 04/27/2022] [Indexed: 01/27/2023] Open
Abstract
Studies indicate that the intestinal microbiota influences general metabolic processes in humans, thereby modulating the risk of chronic diseases such as type 2 diabetes, allergy, cardiovascular disease, and colorectal cancer (CRC). Dietary factors are also directly related to chronic disease risk, and they affect the composition and function of the gut microbiota. Still, detailed knowledge on the relation between diet, the microbiota, and chronic disease risk is limited. The overarching aim of the HDHL-INTIMIC (INtesTInal MICrobiomics) knowledge platform is to foster studies on the microbiota, nutrition, and health by assembling available knowledge of the microbiota and of the other aspects (e.g., food science and metabolomics) that are relevant in the context of microbiome research. The goal is to make this information findable, accessible, interoperable, and reusable (FAIR) to the scientific community, and to share information with the various stakeholders. Through these efforts a network of transnational and multidisciplinary collaboration has emerged, which has contributed to further develop and increase the impact of microbiome research in human health. The roles of microbiota in early infancy, during ageing, and in subclinical and clinically manifested disease are identified as urgent areas of research in this knowledge platform.
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30
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Henneke L, Schlicht K, Andreani NA, Hollstein T, Demetrowitsch T, Knappe C, Hartmann K, Jensen-Kroll J, Rohmann N, Pohlschneider D, Geisler C, Schulte DM, Settgast U, Türk K, Zimmermann J, Kaleta C, Baines JF, Shearer J, Shah S, Shen-Tu G, Schwarz K, Franke A, Schreiber S, Laudes M. A dietary carbohydrate - gut Parasutterella - human fatty acid biosynthesis metabolic axis in obesity and type 2 diabetes. Gut Microbes 2022; 14:2057778. [PMID: 35435797 PMCID: PMC9037427 DOI: 10.1080/19490976.2022.2057778] [Citation(s) in RCA: 83] [Impact Index Per Article: 27.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Recent rodent microbiome experiments suggest that besides Akkermansia, Parasutterella sp. are important in type 2 diabetes and obesity development. In the present translational human study, we aimed to characterize Parasutterella in our European cross-sectional FoCus cohort (n = 1,544) followed by validation of the major results in an independent Canadian cohort (n = 438). In addition, we examined Parasutterella abundance in response to a weight loss intervention (n = 55). Parasutterella was positively associated with BMI and type 2 diabetes independently of the reduced microbiome α/β diversity and low-grade inflammation commonly found in obesity. Nutritional analysis revealed a positive association with the dietary intake of carbohydrates but not with fat or protein consumption. Out of 126 serum metabolites differentially detectable by untargeted HPLC-based MS-metabolomics, L-cysteine showed the strongest reduction in subjects with high Parasutterella abundance. This is of interest, since Parasutterella is a known high L-cysteine consumer and L-cysteine is known to improve blood glucose levels in rodents. Furthermore, metabolic network enrichment analysis identified an association of high Parasutterella abundance with the activation of the human fatty acid biosynthesis pathway suggesting a mechanism for body weight gain. This is supported by a significant reduction of the Parasutterella abundance during our weight loss intervention. Together, these data indicate a role for Parasutterella in human type 2 diabetes and obesity, whereby the link to L-cysteine might be relevant in type 2 diabetes development and the link to the fatty acid biosynthesis pathway for body weight gain in response to a carbohydrate-rich diet in obesity development.
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Affiliation(s)
- Lea Henneke
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Kristina Schlicht
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Nadia A. Andreani
- Section of Evolutionary Medicine, Institute for Experimental Medicine University of Kiel, Kiel, Germany,Guest group for evolutionary medicine Max-Planck-Institute of Evolutionary Biology, Plön, Germany
| | - Tim Hollstein
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Tobias Demetrowitsch
- Division of Food Technology, Department of Human Nutrition, University of Kiel, Kiel, Germany
| | - Carina Knappe
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Katharina Hartmann
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Julia Jensen-Kroll
- Division of Food Technology, Department of Human Nutrition, University of Kiel, Kiel, Germany
| | - Nathalie Rohmann
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Daniela Pohlschneider
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Corinna Geisler
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Dominik M. Schulte
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Ute Settgast
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Kathrin Türk
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Johannes Zimmermann
- Research Group Medical System Biology, Institute of Experimental Medicine, University of Kiel, Kiel, Germany
| | - Christoph Kaleta
- Research Group Medical System Biology, Institute of Experimental Medicine, University of Kiel, Kiel, Germany
| | - John F. Baines
- Section of Evolutionary Medicine, Institute for Experimental Medicine University of Kiel, Kiel, Germany,Guest group for evolutionary medicine Max-Planck-Institute of Evolutionary Biology, Plön, Germany
| | - Jane Shearer
- Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Faculty Kinesiology, University of Calgary, Calgary, Alberta, Canada
| | - Shrushti Shah
- Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Faculty Kinesiology, University of Calgary, Calgary, Alberta, Canada
| | - Grace Shen-Tu
- Alberta’s Tomorrow Project, Cancer Control Alberta, Alberta Health Services, Edmonton, AB, Canada
| | - Karin Schwarz
- Division of Food Technology, Department of Human Nutrition, University of Kiel, Kiel, Germany
| | - Andre Franke
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
| | - Stefan Schreiber
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
| | - Matthias Laudes
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany,Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, University Medical Centre Schleswig-Holstein, Kiel University, Kiel, Germany,CONTACT Matthias Laudes Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Düsternbrooker Weg 17, 24105Kiel, Germany
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31
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Barone M, D'Amico F, Brigidi P, Turroni S. Gut microbiome-micronutrient interaction: The key to controlling the bioavailability of minerals and vitamins? Biofactors 2022; 48:307-314. [PMID: 35294077 PMCID: PMC9311823 DOI: 10.1002/biof.1835] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 02/23/2022] [Indexed: 12/19/2022]
Abstract
Micronutrients, namely, vitamins and minerals, are necessary for the proper functioning of the human body, and their deficiencies can have dramatic short- and long-term health consequences. Among the underlying causes, certainly a reduced dietary intake and/or poor absorption in the gastrointestinal tract play a key role in decreasing their bioavailability. Recent evidence from clinical and in vivo studies suggests an increasingly important contribution from the gut microbiome. Commensal microorganisms can in fact regulate the levels of micronutrients, both by intervening in the biosynthetic processes and by modulating their absorption. This short narrative review addresses the pivotal role of the gut microbiome in influencing the bioavailability of vitamins (such as A, B, C, D, E, and K) and minerals (calcium, iron, zinc, magnesium, and phosphorous), as well as the impact of these micronutrients on microbiome composition and functionality. Personalized microbiome-based intervention strategies could therefore constitute an innovative tool to counteract micronutrient deficiencies by modulating the gut microbiome toward an eubiotic configuration capable of satisfying the needs of our organism, while promoting general health.
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Affiliation(s)
- Monica Barone
- Microbiomics Unit, Department of Medical and Surgical SciencesUniversity of BolognaBolognaItaly
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and BiotechnologyUniversity of BolognaBolognaItaly
| | - Federica D'Amico
- Microbiomics Unit, Department of Medical and Surgical SciencesUniversity of BolognaBolognaItaly
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and BiotechnologyUniversity of BolognaBolognaItaly
| | - Patrizia Brigidi
- Microbiomics Unit, Department of Medical and Surgical SciencesUniversity of BolognaBolognaItaly
| | - Silvia Turroni
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and BiotechnologyUniversity of BolognaBolognaItaly
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32
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Voland L, Le Roy T, Debédat J, Clément K. Gut microbiota and vitamin status in persons with obesity: A key interplay. Obes Rev 2022; 23:e13377. [PMID: 34767276 DOI: 10.1111/obr.13377] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 10/04/2021] [Accepted: 10/05/2021] [Indexed: 12/28/2022]
Abstract
There are numerous factors involved in obesity progression and maintenance including systemic low-grade inflammation, adipose tissue dysfunction, or gut microbiota dysbiosis. Recently, a growing interest has arisen for vitamins' role in obesity and related disorders, both at the host and gut bacterial level. Indeed, vitamins are provided mostly by food, but some, from the B and K groups in particular, can be synthesized by the gut bacterial ecosystem and absorbed in the colon. Knowing that vitamin deficiency can alter many important cellular functions and lead to serious health issues, it is important to carefully monitor the vitamin status of patients with obesity and potentially already existing comorbidities as well as to examine the dysbiotic gut microbiota and thus potentially altered bacterial metabolism of vitamins. In this review, we examined both murine and human studies, to assess the prevalence of sub-optimal levels of several vitamins in obesity and metabolic alterations. This review also examines the relationship between vitamins and the gut microbiota in terms of vitamin production and the modulation of the gut bacterial ecosystem in conditions of vitamin shortage or supplementation. Furthermore, some strategies to improve vitamin status of patients with severe obesity are proposed within this review.
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Affiliation(s)
- Lise Voland
- Inserm, Sorbonne University, Nutrition and obesities: systemic approaches (NutriOmics), Paris, France
| | - Tiphaine Le Roy
- Inserm, Sorbonne University, Nutrition and obesities: systemic approaches (NutriOmics), Paris, France
| | - Jean Debédat
- Inserm, Sorbonne University, Nutrition and obesities: systemic approaches (NutriOmics), Paris, France
| | - Karine Clément
- Inserm, Sorbonne University, Nutrition and obesities: systemic approaches (NutriOmics), Paris, France.,Public hospital of Paris, Nutrition department, Pitié-Salpêtrière Hospital, Paris, France
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33
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Pham VT, Fehlbaum S, Seifert N, Richard N, Bruins MJ, Sybesma W, Rehman A, Steinert RE. Effects of colon-targeted vitamins on the composition and metabolic activity of the human gut microbiome- a pilot study. Gut Microbes 2022; 13:1-20. [PMID: 33615992 PMCID: PMC7899684 DOI: 10.1080/19490976.2021.1875774] [Citation(s) in RCA: 74] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
An increasing body of evidence has shown that gut microbiota imbalances are linked to diseases. Currently, the possibility of regulating gut microbiota to reverse these perturbations by developing novel therapeutic and preventive strategies is being extensively investigated. The modulatory effect of vitamins on the gut microbiome and related host health benefits remain largely unclear. We investigated the effects of colon-delivered vitamins A, B2, C, D, and E on the gut microbiota using a human clinical study and batch fermentation experiments, in combination with cell models for the assessment of barrier and immune functions. Vitamins C, B2, and D may modulate the human gut microbiome in terms of metabolic activity and bacterial composition. The most distinct effect was that of vitamin C, which significantly increased microbial alpha diversity and fecal short-chain fatty acids compared to the placebo. The remaining vitamins tested showed similar effects on microbial diversity, composition, and/or metabolic activity in vitro, but in varying degrees. Here, we showed that vitamins may modulate the human gut microbiome. Follow-up studies investigating targeted delivery of vitamins to the colon may help clarify the clinical significance of this novel concept for treating and preventing dysbiotic microbiota-related human diseases. Trial registration: ClinicalTrials.gov, NCT03668964. Registered 13 September 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03668964.
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Affiliation(s)
- Van T. Pham
- R&D Human Nutrition and Health, DSM Nutritional Products Ltd., Basel, Switzerland,CONTACT Van T. Pham Wurmisweg 576, 4303 Kaiseraugst203/117A+41 618 158 828
| | - Sophie Fehlbaum
- R&D Human Nutrition and Health, DSM Nutritional Products Ltd., Basel, Switzerland
| | - Nicole Seifert
- R&D Human Nutrition and Health, DSM Nutritional Products Ltd., Basel, Switzerland
| | - Nathalie Richard
- R&D Human Nutrition and Health, DSM Nutritional Products Ltd., Basel, Switzerland
| | - Maaike J. Bruins
- R&D Human Nutrition and Health, DSM Nutritional Products Ltd., Basel, Switzerland
| | - Wilbert Sybesma
- R&D Human Nutrition and Health, DSM Nutritional Products Ltd., Basel, Switzerland
| | - Ateequr Rehman
- R&D Human Nutrition and Health, DSM Nutritional Products Ltd., Basel, Switzerland
| | - Robert E. Steinert
- R&D Human Nutrition and Health, DSM Nutritional Products Ltd., Basel, Switzerland,Department of Surgery, Division of Visceral and Transplantation Surgery, University Hospital Zurich, Zurich, Switzerland
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34
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Akimbekov NS, Digel I, Razzaque MS. Role of Vitamins in Maintaining Structure and Function of Intestinal Microbiome. COMPREHENSIVE GUT MICROBIOTA 2022:320-334. [DOI: 10.1016/b978-0-12-819265-8.00043-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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35
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Yuan Y, He N, Dong L, Guo Q, Zhang X, Li B, Li L. Multiscale Shellac-Based Delivery Systems: From Macro- to Nanoscale. ACS NANO 2021; 15:18794-18821. [PMID: 34806863 DOI: 10.1021/acsnano.1c07121] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Delivery systems play a crucial role in enhancing the activity of active substances; however, they require complex processing techniques and raw material design to achieve the desired properties. In this regard, raw materials that can be easily processed for different delivery systems are garnering attention. Among these raw materials, shellac, which is the only pharmaceutically used resin of animal origin, has been widely used in the development of various delivery systems owing to its pH responsiveness, biocompatibility, and degradability. Notably, shellac performs better on encapsulating hydrophobic active substances than other natural polymers, such as polysaccharides and proteins. In addition, specially designed shellac-based delivery systems can also be used for the codelivery of hydrophilic and hydrophobic active substances. Shellac is most widely used for oral administration, as shellac-based delivery systems can form a compact structure through hydrophobic interaction, protecting transported active substances from the harsh environment of the stomach to achieve targeted delivery in the small intestine or colon. In this review, the advantages of shellac in delivery systems are discussed in detail. Multiscale shellac-based delivery systems from the macroscale to nanoscale are comprehensively introduced, including matrix tablets, films, enteric coatings, hydrogels, microcapsules, microparticles (beads/spheres), nanoparticles, and nanofibers. Furthermore, the hotspots, deficiencies, and future perspectives of shellac-based delivery system development are also analyzed. We hoped this review will increase the understanding of shellac-based delivery systems and inspire their further development.
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Affiliation(s)
- Yi Yuan
- School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, South China University of Technology, Guangzhou 510640, China
- Engineering Research Center of Starch and Plant Protein Deep Processing, Ministry of Education, South China University of Technology, Guangzhou 510640, China
| | - Ni He
- School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, South China University of Technology, Guangzhou 510640, China
- Engineering Research Center of Starch and Plant Protein Deep Processing, Ministry of Education, South China University of Technology, Guangzhou 510640, China
| | - Liya Dong
- School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, South China University of Technology, Guangzhou 510640, China
- Engineering Research Center of Starch and Plant Protein Deep Processing, Ministry of Education, South China University of Technology, Guangzhou 510640, China
| | - Qiyong Guo
- School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, South China University of Technology, Guangzhou 510640, China
- Engineering Research Center of Starch and Plant Protein Deep Processing, Ministry of Education, South China University of Technology, Guangzhou 510640, China
| | - Xia Zhang
- School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, South China University of Technology, Guangzhou 510640, China
- Engineering Research Center of Starch and Plant Protein Deep Processing, Ministry of Education, South China University of Technology, Guangzhou 510640, China
| | - Bing Li
- School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, South China University of Technology, Guangzhou 510640, China
- Engineering Research Center of Starch and Plant Protein Deep Processing, Ministry of Education, South China University of Technology, Guangzhou 510640, China
| | - Lin Li
- School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, South China University of Technology, Guangzhou 510640, China
- Engineering Research Center of Starch and Plant Protein Deep Processing, Ministry of Education, South China University of Technology, Guangzhou 510640, China
- School of Chemical Engineering and Energy Technology, Dongguan University of Technology, Dongguan 523808, China
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36
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Guetterman HM, Huey SL, Knight R, Fox AM, Mehta S, Finkelstein JL. Vitamin B-12 and the Gastrointestinal Microbiome: A Systematic Review. Adv Nutr 2021; 13:S2161-8313(22)00075-8. [PMID: 34612492 PMCID: PMC8970816 DOI: 10.1093/advances/nmab123] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Vitamin B-12 deficiency is a major public health problem affecting individuals across the lifespan, with known hematological, neurological, and obstetric consequences. Emerging evidence suggests that vitamin B-12 may have an important role in other aspects of human health, including the composition and function of the gastrointestinal (gut) microbiome. Vitamin B-12 is synthesized and utilized by bacteria in the human gut microbiome and is required for over a dozen enzymes in bacteria, compared to only two in humans. However, the impact of vitamin B-12 on the gut microbiome has not been established. This systematic review was conducted to examine the evidence that links vitamin B-12 and the gut microbiome. A structured search strategy was used to identify in vitro, animal, and human studies that assessed vitamin B-12 status, dietary intake, or supplementation, and the gut microbiome using culture-independent techniques. A total of 22 studies (3 in vitro, 8 animal, 11 human observational studies) were included. Nineteen studies reported vitamin B-12 intake, status, or supplementation was associated with gut microbiome outcomes, including beta-diversity, alpha-diversity, relative abundance of bacteria, functional capacity, or short chain fatty acid production. Evidence suggests vitamin B-12 may be associated with changes in bacterial abundance. While results from in vitro studies suggest vitamin B-12 may increase alpha-diversity and shift gut microbiome composition (beta-diversity), findings from animal studies and observational human studies were heterogeneous. Based on evidence from in vitro and animal studies, microbiome outcomes may differ by cobalamin form and co-intervention. To date, few prospective observational studies and no randomized trials have been conducted to examine the effects of vitamin B-12 on the human gut microbiome. The impact of vitamin B-12 on the gut microbiome needs to be elucidated to inform screening and public health interventions. Statement of significance: Vitamin B-12 is synthesized and utilized by bacteria in the human gut microbiome and is required by over a dozen enzymes in bacteria. However, to date, no systematic reviews have been conducted to evaluate the impact of vitamin B-12 on the gut microbiome, or its implications for human health.
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Affiliation(s)
| | - Samantha L Huey
- Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA
| | - Rob Knight
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA,Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA,Department of Bioengineering, University of California San Diego, La Jolla, CA, USA,Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
| | - Allison M Fox
- Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA
| | - Saurabh Mehta
- Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA,Division of Epidemiology, Department of Population Health Sciences, Weill Cornell Medical College, New York, NY, USA,Institute for Nutritional Sciences, Global Health, and Technology, Cornell University, Ithaca, NY, USA
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37
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Pham VT, Dold S, Rehman A, Bird JK, Steinert RE. Vitamins, the gut microbiome and gastrointestinal health in humans. Nutr Res 2021; 95:35-53. [PMID: 34798467 DOI: 10.1016/j.nutres.2021.09.001] [Citation(s) in RCA: 126] [Impact Index Per Article: 31.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 09/17/2021] [Accepted: 09/20/2021] [Indexed: 02/07/2023]
Abstract
The gut microbiome plays important roles in the maintenance of host health and the pathogenesis of many diseases. Diet is a key modulator of the gut microbiome. There is increasing evidence that nutrients other than fermentable fiber affect the gut microbial composition. In this review, we discuss the effects of vitamins on the gut microbiome, and related gastrointestinal health, based on in vitro, animal and human studies. Some vitamins, when provided in large doses or when delivered to the large intestine, have been shown to beneficially modulate the gut microbiome by increasing the abundance of presumed commensals (vitamins A, B2, D, E, and beta-carotene), increasing or maintaining microbial diversity (vitamins A, B2, B3, C, K) and richness (vitamin D), increasing short chain fatty acid production (vitamin C), or increasing the abundance of short chain fatty acid producers (vitamins B2, E). Others, such as vitamins A and D, modulate the gut immune response or barrier function, thus, indirectly influencing gastrointestinal health or the microbiome. Future research is needed to explore these potential effects and to elucidate the underlying mechanisms and host health benefits.
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Affiliation(s)
- Van T Pham
- DSM Nutritional Products, Kaiseraugst, Switzerland.
| | - Susanne Dold
- DSM Nutritional Products, Kaiseraugst, Switzerland
| | | | | | - Robert E Steinert
- DSM Nutritional Products, Kaiseraugst, Switzerland; Department of Surgery, Division of Visceral and Transplantation Surgery, University Hospital Zurich, Zurich, Switzerland
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38
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Microbiota in Health and Disease-Potential Clinical Applications. Nutrients 2021; 13:nu13113866. [PMID: 34836121 PMCID: PMC8622281 DOI: 10.3390/nu13113866] [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: 09/29/2021] [Revised: 10/26/2021] [Accepted: 10/27/2021] [Indexed: 12/11/2022] Open
Abstract
Within the last two decades tremendous efforts in biomedicine have been undertaken to understand the interplay of commensal bacteria living in and on our human body with our own human physiology. It became clear that (1) a high diversity especially of the microbial communities in the gut are important to preserve health and that (2) certain bacteria via nutrition-microbe-host metabolic axes are beneficially affecting various functions of the host, including metabolic control, energy balance and immune function. While a large set of evidence indicate a special role for small chain fatty acids (SCFA) in that context, recently also metabolites of amino acids (e.g., tryptophan and arginine) moved into scientific attention. Of interest, microbiome alterations are not only important in nutrition associated diseases like obesity and diabetes, but also in many chronic inflammatory, oncological and neurological abnormalities. From a clinician’s point of view, it should be mentioned, that the microbiome is not only interesting to develop novel therapies, but also as a modifiable factor to improve efficiency of modern pharmaceutics, e.g., immune-therapeutics in oncology. However, so far, most data rely on animal experiments or human association studies, whereas controlled clinical intervention studies are spare. Hence, the translation of the knowledge of the last decades into clinical routine will be the challenge of microbiome based biomedical research for the next years. This review aims to provide examples for future clinical applications in various entities and to suggest bacterial species and/or microbial effector molecules as potential targets for intervention studies.
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39
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Pinart M, Nimptsch K, Forslund SK, Schlicht K, Gueimonde M, Brigidi P, Turroni S, Ahrens W, Hebestreit A, Wolters M, Dötsch A, Nöthlings U, Oluwagbemigun K, Cuadrat RRC, Schulze MB, Standl M, Schloter M, De Angelis M, Iozzo P, Guzzardi MA, Vlaemynck G, Penders J, Jonkers DMAE, Stemmer M, Chiesa G, Cavalieri D, De Filippo C, Ercolini D, De Filippis F, Ribet D, Achamrah N, Tavolacci MP, Déchelotte P, Bouwman J, Laudes M, Pischon T. Identification and Characterization of Human Observational Studies in Nutritional Epidemiology on Gut Microbiomics for Joint Data Analysis. Nutrients 2021; 13:3292. [PMID: 34579168 PMCID: PMC8466729 DOI: 10.3390/nu13093292] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 09/10/2021] [Accepted: 09/17/2021] [Indexed: 01/16/2023] Open
Abstract
In any research field, data access and data integration are major challenges that even large, well-established consortia face. Although data sharing initiatives are increasing, joint data analyses on nutrition and microbiomics in health and disease are still scarce. We aimed to identify observational studies with data on nutrition and gut microbiome composition from the Intestinal Microbiomics (INTIMIC) Knowledge Platform following the findable, accessible, interoperable, and reusable (FAIR) principles. An adapted template from the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) consortium was used to collect microbiome-specific information and other related factors. In total, 23 studies (17 longitudinal and 6 cross-sectional) were identified from Italy (7), Germany (6), Netherlands (3), Spain (2), Belgium (1), and France (1) or multiple countries (3). Of these, 21 studies collected information on both dietary intake (24 h dietary recall, food frequency questionnaire (FFQ), or Food Records) and gut microbiome. All studies collected stool samples. The most often used sequencing platform was Illumina MiSeq, and the preferred hypervariable regions of the 16S rRNA gene were V3-V4 or V4. The combination of datasets will allow for sufficiently powered investigations to increase the knowledge and understanding of the relationship between food and gut microbiome in health and disease.
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Affiliation(s)
- Mariona Pinart
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; (M.P.); (T.P.)
| | - Katharina Nimptsch
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; (M.P.); (T.P.)
| | - Sofia K. Forslund
- Experimental and Clinical Research Center, A Cooperation of Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Lindenberger Weg 80, 13125 Berlin, Germany;
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, 10117 Berlin, Germany
- Host-Microbiome Factors in Cardiovascular Disease Lab, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, 10785 Berlin, Germany
- Berlin Institute of Health (BIH), 10178 Berlin, Germany
- Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany
| | - Kristina Schlicht
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, 24105 Kiel, Germany; (K.S.); (M.L.)
| | - Miguel Gueimonde
- Department of Microbiology and Biochemistry of Dairy Products, IPLA-CSIC, 33300 Villaviciosa, Spain;
- Diet, Microbiota and Health Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain
| | - Patrizia Brigidi
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy;
| | - Silvia Turroni
- Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy;
| | - Wolfgang Ahrens
- Leibniz Institute for Prevention Research and Epidemiology-BIPS, 28359 Bremen, Germany; (W.A.); (A.H.); (M.W.)
- Institute of Statistics, Bremen University, 28359 Bremen, Germany
| | - Antje Hebestreit
- Leibniz Institute for Prevention Research and Epidemiology-BIPS, 28359 Bremen, Germany; (W.A.); (A.H.); (M.W.)
| | - Maike Wolters
- Leibniz Institute for Prevention Research and Epidemiology-BIPS, 28359 Bremen, Germany; (W.A.); (A.H.); (M.W.)
| | - Andreas Dötsch
- Department of Physiology and Biochemistry of Nutrition, Max Rubner-Institut (MRI)-Federal Research Institute of Nutrition and Food, 76131 Karlsruhe, Germany;
| | - Ute Nöthlings
- Nutritional Epidemiology Unit, Institute of Nutrition and Food Sciences, University of Bonn, 53115 Bonn, Germany; (U.N.); (K.O.)
| | - Kolade Oluwagbemigun
- Nutritional Epidemiology Unit, Institute of Nutrition and Food Sciences, University of Bonn, 53115 Bonn, Germany; (U.N.); (K.O.)
| | - Rafael R. C. Cuadrat
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany; (R.R.C.C.); (M.B.S.)
| | - Matthias B. Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany; (R.R.C.C.); (M.B.S.)
- Institute of Nutritional Science, University of Potsdam, 14558 Potsdam, Germany
- German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
| | - Marie Standl
- Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, 85764 Neuherberg, Germany;
| | - Michael Schloter
- Research Unit for Comparative Microbiome Analysis, Helmholtz Zentrum München-German Research Center for Environmental Health, 85764 Neuherberg, Germany;
| | - Maria De Angelis
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, 70126 Bari, Italy;
| | - Patricia Iozzo
- Institute of Clinical Physiology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy; (P.I.); (M.A.G.)
| | - Maria Angela Guzzardi
- Institute of Clinical Physiology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy; (P.I.); (M.A.G.)
| | - Geertrui Vlaemynck
- Department Technology and Food, Flanders Research Institute for Agriculture, Fisheries and Food, 9090 Melle, Belgium;
| | - John Penders
- Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM) and Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands;
| | - Daisy M. A. E. Jonkers
- Department of Internal Medicine, Division Gastroenterology-Hepatology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands;
| | - Maya Stemmer
- Department of Industrial Engineering and Management, Ben-Gurion University of the Negev, Beer-Sheva P.O. Box 653, Israel;
| | - Giulia Chiesa
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy;
| | - Duccio Cavalieri
- Department of Biology, University of Florence, Via Madonna del Piano 6, 50019 Florence, Italy;
| | - Carlotta De Filippo
- Institute of Agricultural Biology and Biotechnology National Research Council, Via Moruzzi 1, 56124 Pisa, Italy;
| | - Danilo Ercolini
- Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy; (D.E.); (F.D.F.)
- Task Force on Microbiome Studies, University of Naples Federico II, 80134 Naples, Italy
| | - Francesca De Filippis
- Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy; (D.E.); (F.D.F.)
- Task Force on Microbiome Studies, University of Naples Federico II, 80134 Naples, Italy
| | - David Ribet
- INSERM UMR 1073 “Nutrition, Inflammation and Gut-Brain Axis Dysfunctions”, UNIROUEN, Normandie University, 76000 Rouen, France; (D.R.); (N.A.); (M.-P.T.); (P.D.)
| | - Najate Achamrah
- INSERM UMR 1073 “Nutrition, Inflammation and Gut-Brain Axis Dysfunctions”, UNIROUEN, Normandie University, 76000 Rouen, France; (D.R.); (N.A.); (M.-P.T.); (P.D.)
- Department of Nutrition, CHU Rouen, 76000 Rouen, France
| | - Marie-Pierre Tavolacci
- INSERM UMR 1073 “Nutrition, Inflammation and Gut-Brain Axis Dysfunctions”, UNIROUEN, Normandie University, 76000 Rouen, France; (D.R.); (N.A.); (M.-P.T.); (P.D.)
- INSERM CIC-CRB 1404, CHU Rouen, 76000 Rouen, France
| | - Pierre Déchelotte
- INSERM UMR 1073 “Nutrition, Inflammation and Gut-Brain Axis Dysfunctions”, UNIROUEN, Normandie University, 76000 Rouen, France; (D.R.); (N.A.); (M.-P.T.); (P.D.)
- Department of Nutrition, CHU Rouen, 76000 Rouen, France
| | - Jildau Bouwman
- Microbiology and Systems Biology Group, TNO, Utrechtseweg 48, 3704 HE Zeist, The Netherlands;
| | - Matthias Laudes
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, 24105 Kiel, Germany; (K.S.); (M.L.)
| | - Tobias Pischon
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; (M.P.); (T.P.)
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, 10117 Berlin, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, 10785 Berlin, Germany
- Biobank Technology Platform, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany
- Biobank Core Facility, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, 10178 Berlin, Germany
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40
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Dowdell AS, Colgan SP. Metabolic Host-Microbiota Interactions in Autophagy and the Pathogenesis of Inflammatory Bowel Disease (IBD). Pharmaceuticals (Basel) 2021; 14:708. [PMID: 34451805 PMCID: PMC8399382 DOI: 10.3390/ph14080708] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 07/15/2021] [Accepted: 07/16/2021] [Indexed: 12/17/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a family of conditions characterized by chronic, relapsing inflammation of the gastrointestinal tract. IBD afflicts over 3 million adults in the United States and shows increasing prevalence in the Westernized world. Current IBD treatments center on modulation of the damaging inflammatory response and carry risks such as immunosuppression, while the development of more effective treatments is hampered by our poor understanding of the molecular mechanisms of IBD pathogenesis. Previous genome-wide association studies (GWAS) have demonstrated that gene variants linked to the cellular response to microorganisms are most strongly associated with an increased risk of IBD. These studies are supported by mechanistic work demonstrating that IBD-associated polymorphisms compromise the intestine's anti-microbial defense. In this review, we summarize the current knowledge regarding IBD as a disease of defects in host-microbe interactions and discuss potential avenues for targeting this mechanism for future therapeutic development.
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Affiliation(s)
| | - Sean P. Colgan
- Department of Medicine and the Mucosal Inflammation Program, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA;
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41
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Carlan IC, Estevinho BN, Rocha F. Innovation and improvement in food fortification: Microencapsulation of vitamin B2 and B3 by a spray-drying method and evaluation of the simulated release profiles. J DISPER SCI TECHNOL 2021. [DOI: 10.1080/01932691.2021.1924768] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Affiliation(s)
- Ioana C. Carlan
- LEPABE, Departamento de Engenharia Química, Faculdade de Engenharia da Universidade do Porto, Porto, Portugal
| | - Berta N. Estevinho
- LEPABE, Departamento de Engenharia Química, Faculdade de Engenharia da Universidade do Porto, Porto, Portugal
| | - Fernando Rocha
- LEPABE, Departamento de Engenharia Química, Faculdade de Engenharia da Universidade do Porto, Porto, Portugal
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42
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Pham VT, Calatayud M, Rotsaert C, Seifert N, Richard N, Van den Abbeele P, Marzorati M, Steinert RE. Antioxidant Vitamins and Prebiotic FOS and XOS Differentially Shift Microbiota Composition and Function and Improve Intestinal Epithelial Barrier In Vitro. Nutrients 2021; 13:nu13041125. [PMID: 33805552 PMCID: PMC8066074 DOI: 10.3390/nu13041125] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 03/22/2021] [Accepted: 03/25/2021] [Indexed: 12/14/2022] Open
Abstract
Human gut microbiota (HGM) play a significant role in health and disease. Dietary components, including fiber, fat, proteins and micronutrients, can modulate HGM. Much research has been performed on conventional prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), however, novel prebiotics or micronutrients still require further validation. We assessed the effect of FOS, xylooligosaccharides (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro. We used batch fermentations and tested the short-term effect of different products on microbial activity in six donors. Next, fecal inocula from two donors were used to inoculate the simulator of the human microbial ecosystem (SHIME) and after long-term exposure of FOS, XOS and AOB, microbial activity (short- and branched-chain fatty acids and lactate) and HGM composition were evaluated. Finally, in vitro assessment of intestinal barrier was performed in a Transwell setup of differentiated Caco-2 and HT29-MTX-E12 cells exposed to fermentation supernatants. Despite some donor-dependent differences, all three tested products showed beneficial modulatory effects on microbial activity represented by an increase in lactate and SCFA levels (acetate, butyrate and to a lesser extent also propionate), while decreasing proteolytic markers. Bifidogenic effect of XOS was consistent, while AOB supplementation appears to exert a specific impact on reducing F. nucleatum and increasing butyrate-producing B. wexlerae. Functional and compositional microbial changes were translated to an in vitro host response by increases of the intestinal barrier integrity by all the products and a decrease of the redox potential by AOB supplementation.
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Affiliation(s)
- Van T. Pham
- R&D Human Nutrition and Health, DSM Nutritional Products Ltd., 4002 Basel, Switzerland; (N.S.); (N.R.); (R.E.S.)
- Correspondence: ; Tel.: +41-618-158-828
| | - Marta Calatayud
- ProDigest BV, Technologiepark 82, 9052 Ghent, Belgium; (M.C.); (C.R.); (P.V.d.A.); (M.M.)
| | - Chloë Rotsaert
- ProDigest BV, Technologiepark 82, 9052 Ghent, Belgium; (M.C.); (C.R.); (P.V.d.A.); (M.M.)
| | - Nicole Seifert
- R&D Human Nutrition and Health, DSM Nutritional Products Ltd., 4002 Basel, Switzerland; (N.S.); (N.R.); (R.E.S.)
| | - Nathalie Richard
- R&D Human Nutrition and Health, DSM Nutritional Products Ltd., 4002 Basel, Switzerland; (N.S.); (N.R.); (R.E.S.)
| | - Pieter Van den Abbeele
- ProDigest BV, Technologiepark 82, 9052 Ghent, Belgium; (M.C.); (C.R.); (P.V.d.A.); (M.M.)
| | - Massimo Marzorati
- ProDigest BV, Technologiepark 82, 9052 Ghent, Belgium; (M.C.); (C.R.); (P.V.d.A.); (M.M.)
- Center for Microbial Ecology and Technology (CMET), Department of Biotechnology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
| | - Robert E. Steinert
- R&D Human Nutrition and Health, DSM Nutritional Products Ltd., 4002 Basel, Switzerland; (N.S.); (N.R.); (R.E.S.)
- Department of Surgery, Division of Visceral and Transplantation Surgery, University Hospital Zurich, 8006 Zurich, Switzerland
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43
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Cunningham M, Azcarate-Peril MA, Barnard A, Benoit V, Grimaldi R, Guyonnet D, Holscher HD, Hunter K, Manurung S, Obis D, Petrova MI, Steinert RE, Swanson KS, van Sinderen D, Vulevic J, Gibson GR. Shaping the Future of Probiotics and Prebiotics. Trends Microbiol 2021; 29:667-685. [PMID: 33551269 DOI: 10.1016/j.tim.2021.01.003] [Citation(s) in RCA: 284] [Impact Index Per Article: 71.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 01/05/2021] [Accepted: 01/06/2021] [Indexed: 12/15/2022]
Abstract
Recent and ongoing developments in microbiome science are enabling new frontiers of research for probiotics and prebiotics. Novel types, mechanisms, and applications currently under study have the potential to change scientific understanding as well as nutritional and healthcare applications of these interventions. The expansion of related fields of microbiome-targeted interventions, and an evolving landscape for implementation across regulatory, policy, prescriber, and consumer spheres, portends an era of significant change. In this review we examine recent, emerging, and anticipated trends in probiotic and prebiotic science, and create a vision for broad areas of developing influence in the field.
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Affiliation(s)
- Marla Cunningham
- Department of Science and Innovation, Metagenics, PO Box 675, Virginia BC, QLD, 4014, Australia.
| | - M Andrea Azcarate-Peril
- UNC Departments of Medicine and Nutrition, Microbiome Core Facility, University of North Carolina, Chapel Hill, NC, USA
| | | | - Valerie Benoit
- Bell Institute of Health and Nutrition, General Mills, Minneapolis, MN, USA
| | | | - Denis Guyonnet
- Diana Nova, Symrise Nutrition, Clichy-la-Garenne, France
| | - Hannah D Holscher
- Department of Food Science and Human Nutrition and Division of Nutritional Sciences, University of Illinois, Urbana, IL, USA
| | - Kirsty Hunter
- Department of Sport Science, Nottingham Trent University, UK
| | - Sarmauli Manurung
- Emerging Sciences Research, Reckitt Benckiser, Nijmegen, The Netherlands
| | - David Obis
- Danone Nutricia Research, Palaiseau Cedex, France
| | | | - Robert E Steinert
- R&D Human Nutrition and Health, DSM Nutritional Products Ltd, Basel, Switzerland; Department of Surgery, Division of Visceral and Transplantation Surgery, University Hospital Zürich, Switzerland
| | - Kelly S Swanson
- Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
| | - Douwe van Sinderen
- Microbiology BioSciences Institute, University College Cork, Cork, Ireland
| | - Jelena Vulevic
- veMico Ltd, Reading, UK; Department of Food and Nutritional Sciences, University of Reading, Reading, UK
| | - Glenn R Gibson
- Department of Food and Nutritional Sciences, University of Reading, Reading, UK
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44
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Balvers M, van den Born BJH, Levin E, Nieuwdorp M. Impact drugs targeting cardiometabolic risk on the gut microbiota. Curr Opin Lipidol 2021; 32:38-54. [PMID: 33332920 DOI: 10.1097/mol.0000000000000727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
PURPOSE OF REVIEW Alterations in the gut microbiome composition or function are associated with risk factors for cardiometabolic diseases, including hypertension, hyperlipidemia and hyperglycemia. Based on recent evidence that also oral medications used to treat these conditions could alter the gut microbiome composition and function and, vice versa, that the gut microbiome could affect the efficacy of these treatments, we reviewed the literature on these observed interactions. RECENT FINDINGS While the interaction of metformin with the gut microbiome has been studied most, other drugs that target cardiometabolic risk are gaining attention and often showed associations with alterations in microbiome-related features, including alterations in specific microbial taxa or pathways, microbiome composition or microbiome-derived metabolites, while the gut microbiome was also involved in drug metabolism and drug efficacy. As for metformin, for some of them even a potential therapeutic effect via the gut microbiome is postulated. However, exact mechanisms remain to be elucidated. SUMMARY There is growing interest in clarifying the interactions between the gut microbiome and drugs to treat hypertension, hyperlipidemia and hyperglycemia as well as the first pass effect of microbiome on drug efficacy. While mostly analysed in animal models, also human studies are gaining more and more traction. Improving the understanding of the gut microbiome drug interaction can provide clinical directions for therapy by optimizing drug efficacy or providing new targets for drug development.
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Affiliation(s)
- Manon Balvers
- Department of Internal and Vascular Medicine, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam
- Horaizon BV, Delft
| | - Bert-Jan H van den Born
- Department of Internal and Vascular Medicine, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam
- Department of Public Health, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Evgeni Levin
- Department of Internal and Vascular Medicine, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam
- Horaizon BV, Delft
| | - Max Nieuwdorp
- Department of Internal and Vascular Medicine, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam
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45
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Kundra P, Rachmühl C, Lacroix C, Geirnaert A. Role of Dietary Micronutrients on Gut Microbial Dysbiosis and Modulation in Inflammatory Bowel Disease. Mol Nutr Food Res 2021. [DOI: 10.1002/mnfr.201901271] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Palni Kundra
- Laboratory of Food Biotechnology Institute of Food Nutrition and Health Schmelzbergstrasse 7 Zürich 8092 Switzerland
| | - Carole Rachmühl
- Laboratory of Food Biotechnology Institute of Food Nutrition and Health Schmelzbergstrasse 7 Zürich 8092 Switzerland
| | - Christophe Lacroix
- Laboratory of Food Biotechnology Institute of Food Nutrition and Health Schmelzbergstrasse 7 Zürich 8092 Switzerland
| | - Annelies Geirnaert
- Laboratory of Food Biotechnology Institute of Food Nutrition and Health Schmelzbergstrasse 7 Zürich 8092 Switzerland
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46
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Leblhuber F, Ehrlich D, Steiner K, Geisler S, Fuchs D, Lanser L, Kurz K. The Immunopathogenesis of Alzheimer's Disease Is Related to the Composition of Gut Microbiota. Nutrients 2021; 13:361. [PMID: 33504065 PMCID: PMC7912578 DOI: 10.3390/nu13020361] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 01/14/2021] [Accepted: 01/20/2021] [Indexed: 12/11/2022] Open
Abstract
The microbiota-gut-brain axis plays an important role in the development of neurodegenerative diseases. Commensal and pathogenic enteric bacteria can influence brain and immune system function by the production of lipopolysaccharides and amyloid. Dysbiosis of the intestinal microbiome induces local and consecutively systemic immune-mediated inflammation. Proinflammatory cytokines then trigger neuroinflammation and finally neurodegeneration. Immune-mediated oxidative stress can lead to a deficiency of vitamins and essential micronutrients. Furthermore, the wrong composition of gut microbiota might impair the intake and metabolization of nutrients. In patients with Alzheimer's disease (AD) significant alterations of the gut microbiota have been demonstrated. Standard Western diet, infections, decreased physical activity and chronic stress impact the composition and diversity of gut microbiota. A higher abundancy of "pro-inflammatory" gut microbiota goes along with enhanced systemic inflammation and neuroinflammatory processes. Thus, AD beginning in the gut is closely related to the imbalance of gut microbiota. Modulation of gut microbiota by Mediterranean diet, probiotics and curcumin can slow down cognitive decline and alter the gut microbiome significantly. A multi-domain intervention approach addressing underlying causes of AD (inflammation, infections, metabolic alterations like insulin resistance and nutrient deficiency, stress) appears very promising to reduce or even reverse cognitive decline by exerting positive effects on the gut microbiota.
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Affiliation(s)
- Friedrich Leblhuber
- Department of Gerontology, Neuromed Campus, Kepler University Clinic, Linz A-4020, Austria; (F.L.); (D.E.); (K.S.)
| | - Daniela Ehrlich
- Department of Gerontology, Neuromed Campus, Kepler University Clinic, Linz A-4020, Austria; (F.L.); (D.E.); (K.S.)
| | - Kostja Steiner
- Department of Gerontology, Neuromed Campus, Kepler University Clinic, Linz A-4020, Austria; (F.L.); (D.E.); (K.S.)
| | - Simon Geisler
- Institute of Biological Chemistry, Biocenter, Medical University of Innsbruck, Innsbruck A-6020, Austria; (S.G.); (D.F.)
| | - Dietmar Fuchs
- Institute of Biological Chemistry, Biocenter, Medical University of Innsbruck, Innsbruck A-6020, Austria; (S.G.); (D.F.)
| | - Lukas Lanser
- Department of Internal Medicine, Medical University of Innsbruck, Innsbruck A-6020, Austria;
| | - Katharina Kurz
- Department of Internal Medicine, Medical University of Innsbruck, Innsbruck A-6020, Austria;
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47
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Singh P, Rawat A, Alwakeel M, Sharif E, Al Khodor S. The potential role of vitamin D supplementation as a gut microbiota modifier in healthy individuals. Sci Rep 2020; 10:21641. [PMID: 33303854 PMCID: PMC7729960 DOI: 10.1038/s41598-020-77806-4] [Citation(s) in RCA: 126] [Impact Index Per Article: 25.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 11/13/2020] [Indexed: 02/06/2023] Open
Abstract
Vitamin D deficiency affects approximately 80% of individuals in some countries and has been linked with gut dysbiosis and inflammation. While the benefits of vitamin D supplementation on the gut microbiota have been studied in patients with chronic diseases, its effects on the microbiota of otherwise healthy individuals is unclear. Moreover, whether effects on the microbiota can explain some of the marked inter-individual variation in responsiveness to vitamin D supplementation is unknown. Here, we administered vitamin D to 80 otherwise healthy vitamin D-deficient women, measuring serum 25(OH) D levels in blood and characterizing their gut microbiota pre- and post- supplementation using 16S rRNA gene sequencing. Vitamin D supplementation significantly increased gut microbial diversity. Specifically, the Bacteroidetes to Firmicutes ratio increased, along with the abundance of the health-promoting probiotic taxa Akkermansia and Bifidobacterium. Significant variations in the two-dominant genera, Bacteroides and Prevotella, indicated a variation in enterotypes following supplementation. Comparing supplementation responders and non-responders we found more pronounced changes in abundance of major phyla in responders, and a significant decrease in Bacteroides acidifaciens in non-responders. Altogether, our study highlights the positive impact of vitamin D supplementation on the gut microbiota and the potential for the microbial gut signature to affect vitamin D response.
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Affiliation(s)
- Parul Singh
- Research Department, Sidra Medicine, Doha, Qatar
| | - Arun Rawat
- Research Department, Sidra Medicine, Doha, Qatar
| | | | - Elham Sharif
- College of Health Sciences, Qatar University, Doha, Qatar.
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48
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Herrema H, Niess JH. Intestinal microbial metabolites in human metabolism and type 2 diabetes. Diabetologia 2020; 63:2533-2547. [PMID: 32880688 PMCID: PMC7641949 DOI: 10.1007/s00125-020-05268-4] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 07/13/2020] [Indexed: 12/12/2022]
Abstract
Humans with the metabolic syndrome and type 2 diabetes have an altered gut microbiome. Emerging evidence indicates that it is not only the microorganisms and their structural components, but also their metabolites that influences the host and contributes to the development of the metabolic syndrome and type 2 diabetes. Here, we discuss some of the mechanisms underlying how microbial metabolites are recognised by the host or are further processed endogenously in the context of type 2 diabetes. We discuss the possibility that gut-derived microbial metabolites fuel the development of the metabolic syndrome and type 2 diabetes. Graphical abstract.
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Affiliation(s)
- Hilde Herrema
- Department of Experimental Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.
| | - Jan Hendrik Niess
- Department of Biomedicine, University of Basel, Hebelstrasse 20, CH-4031, Basel, Switzerland.
- University Center for Gastrointestinal and Liver Diseases, St Clara Hospital and University Hospital of Basel, Basel, Switzerland.
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49
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Demetrowitsch TJ, Schlicht K, Knappe C, Zimmermann J, Jensen-Kroll J, Pisarevskaja A, Brix F, Brandes J, Geisler C, Marinos G, Sommer F, Schulte DM, Kaleta C, Andersen V, Laudes M, Schwarz K, Waschina S. Precision Nutrition in Chronic Inflammation. Front Immunol 2020; 11:587895. [PMID: 33329569 PMCID: PMC7719806 DOI: 10.3389/fimmu.2020.587895] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 10/22/2020] [Indexed: 12/11/2022] Open
Abstract
The molecular foundation of chronic inflammatory diseases (CIDs) can differ markedly between individuals. As our understanding of the biochemical mechanisms underlying individual disease manifestations and progressions expands, new strategies to adjust treatments to the patient's characteristics will continue to profoundly transform clinical practice. Nutrition has long been recognized as an important determinant of inflammatory disease phenotypes and treatment response. Yet empirical work demonstrating the therapeutic effectiveness of patient-tailored nutrition remains scarce. This is mainly due to the challenges presented by long-term effects of nutrition, variations in inter-individual gastrointestinal microbiota, the multiplicity of human metabolic pathways potentially affected by food ingredients, nutrition behavior, and the complexity of food composition. Historically, these challenges have been addressed in both human studies and experimental model laboratory studies primarily by using individual nutrition data collection in tandem with large-scale biomolecular data acquisition (e.g. genomics, metabolomics, etc.). This review highlights recent findings in the field of precision nutrition and their potential implications for the development of personalized treatment strategies for CIDs. It emphasizes the importance of computational approaches to integrate nutritional information into multi-omics data analysis and to predict which molecular mechanisms may explain how nutrients intersect with disease pathways. We conclude that recent findings point towards the unexhausted potential of nutrition as part of personalized medicine in chronic inflammation.
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Affiliation(s)
- Tobias J. Demetrowitsch
- Division of Food Technology, Institute of Human Nutrition and Food Science, Kiel University, Kiel, Germany
| | - Kristina Schlicht
- Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel University, Kiel, Germany
| | - Carina Knappe
- Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel University, Kiel, Germany
| | - Johannes Zimmermann
- Research Group Medical Systems Biology, Institute of Experimental Medicine, Kiel University, Kiel, Germany
| | - Julia Jensen-Kroll
- Division of Food Technology, Institute of Human Nutrition and Food Science, Kiel University, Kiel, Germany
| | - Alina Pisarevskaja
- Division of Food Technology, Institute of Human Nutrition and Food Science, Kiel University, Kiel, Germany
- Division of Nutriinformatics, Institute of Human Nutrition and Food Science, Kiel University, Kiel, Germany
| | - Fynn Brix
- Division of Food Technology, Institute of Human Nutrition and Food Science, Kiel University, Kiel, Germany
| | - Juliane Brandes
- Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel University, Kiel, Germany
| | - Corinna Geisler
- Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel University, Kiel, Germany
| | - Georgios Marinos
- Research Group Medical Systems Biology, Institute of Experimental Medicine, Kiel University, Kiel, Germany
| | - Felix Sommer
- Institute of Clinical Molecular Biology (IKMB), Kiel University, Kiel, Germany
| | - Dominik M. Schulte
- Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel University, Kiel, Germany
| | - Christoph Kaleta
- Research Group Medical Systems Biology, Institute of Experimental Medicine, Kiel University, Kiel, Germany
| | - Vibeke Andersen
- Institute of Regional Research, University of Southern Denmark, Odense, Denmark
- Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
- Focused Research Unit for Molecular Diagnostic and Clinical Research, University Hospital of Southern Denmark, Aabenraa, Denmark
| | - Matthias Laudes
- Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel University, Kiel, Germany
| | - Karin Schwarz
- Division of Food Technology, Institute of Human Nutrition and Food Science, Kiel University, Kiel, Germany
| | - Silvio Waschina
- Division of Nutriinformatics, Institute of Human Nutrition and Food Science, Kiel University, Kiel, Germany
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50
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Solopova A, Bottacini F, Venturi Degli Esposti E, Amaretti A, Raimondi S, Rossi M, van Sinderen D. Riboflavin Biosynthesis and Overproduction by a Derivative of the Human Gut Commensal Bifidobacterium longum subsp. infantis ATCC 15697. Front Microbiol 2020; 11:573335. [PMID: 33042083 PMCID: PMC7522473 DOI: 10.3389/fmicb.2020.573335] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 08/17/2020] [Indexed: 11/18/2022] Open
Abstract
Riboflavin or vitamin B2 is the precursor of the essential coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Despite increased interest in microbial synthesis of this water-soluble vitamin, the metabolic pathway for riboflavin biosynthesis has been characterized in just a handful of bacteria. Here, comparative genome analysis identified the genes involved in the de novo biosynthetic pathway of riboflavin in certain bifidobacterial species, including the human gut commensal Bifidobacterium longum subsp. infantis (B. infantis) ATCC 15697. Using comparative genomics and phylogenomic analysis, we investigated the evolutionary acquisition route of the riboflavin biosynthesis or rib gene cluster in Bifidobacterium and the distribution of riboflavin biosynthesis-associated genes across the genus. Using B. infantis ATCC 15697 as model organism for this pathway, we isolated spontaneous riboflavin overproducers, which had lost transcriptional regulation of the genes required for riboflavin biosynthesis. Among them, one mutant was shown to allow riboflavin release into the medium to a concentration of 60.8 ng mL–1. This mutant increased vitamin B2 concentration in a fecal fermentation system, thus providing promising data for application of this isolate as a functional food ingredient.
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Affiliation(s)
- Ana Solopova
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | | | | | - Alberto Amaretti
- Department of Chemistry, University of Modena and Reggio Emilia, Modena, Italy.,BIOGEST-SITEIA, University of Modena and Reggio Emilia, Modena, Italy
| | - Stefano Raimondi
- Department of Chemistry, University of Modena and Reggio Emilia, Modena, Italy
| | - Maddalena Rossi
- Department of Chemistry, University of Modena and Reggio Emilia, Modena, Italy.,BIOGEST-SITEIA, University of Modena and Reggio Emilia, Modena, Italy
| | - Douwe van Sinderen
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,School of Microbiology, University College Cork, Cork, Ireland
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