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Ganguly S, Chattopadhyay T, Kazi R, Das S, Malik B, Ml U, Iyer PS, Kashiv M, Singh A, Ghadge A, Nair SD, Sonawane MS, Kolthur-Seetharam U. Consumption of sucrose-water rewires macronutrient uptake and utilization mechanisms in a tissue specific manner. J Nutr Biochem 2025; 139:109850. [PMID: 39889860 DOI: 10.1016/j.jnutbio.2025.109850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 10/31/2024] [Accepted: 01/25/2025] [Indexed: 02/03/2025]
Abstract
Consumption of sugar-sweetened beverages (SSBs) have been linked to metabolic dysfunction, obesity, diabetes and enhanced risk of cardiovascular diseases across all age-groups globally. Decades of work that have provided insights into pathophysiological manifestations of sucrose overfeeding have employed paradigms that rarely mimic human consumption of SSBs. Thus, our understanding of multiorgan cross-talk and molecular and/or cellular mechanisms, which operate across scales and drive physiological derangement is still poor. By employing a paradigm of sucrose water feeding in mice that closely resembles chronic SSB consumption in humans (10% sucrose in water), we have unraveled hitherto unknown tissue-specific mechanistic underpinnings, which contribute towards perturbed physiology. Our findings illustrate that systemic impaired glucose homeostasis, mediated by hepatic gluconeogenesis and insulin resistance, does not involve altered gene expression programs in the liver. We have discovered the pivotal role of the small intestine, which in conjunction with liver and muscles, drives dyshomeostasis. Importantly, we have uncovered rewiring of molecular mechanisms in the proximal intestine that is either causal or consequential to systemic ill-effects of chronic sucrose water consumption including dysfunction of liver and muscle mitochondria. Tissue-specific molecular signatures, which we have unveiled as the primary outcome, clearly indicate that inefficient utilization of glucose is exacerbated by enhanced uptake by the gut. Besides providing systems-wide mechanistic insights, we propose that consumption of SSBs causes intestinal 'molecular addiction' for deregulated absorption of hexose-sugars, and drives diseases such as diabetes and obesity.
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Affiliation(s)
- Saptarnab Ganguly
- Tata Institute of Fundamental Research, Subject Board of Biology, Hyderabad, Telangana, India
| | - Tandrika Chattopadhyay
- Centre for innovation in molecular and pharmaceutical sciences, Dr. Reddy's Institute of Life Sciences, Hyderabad, Telangana, India
| | - Rubina Kazi
- Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra, India
| | - Souparno Das
- Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra, India
| | - Bhavisha Malik
- Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra, India
| | - Uthpala Ml
- Tata Institute of Fundamental Research, Subject Board of Biology, Hyderabad, Telangana, India
| | - Padmapriya S Iyer
- Tata Institute of Fundamental Research, Subject Board of Biology, Hyderabad, Telangana, India
| | - Mohit Kashiv
- Tata Institute of Fundamental Research, Subject Board of Biology, Hyderabad, Telangana, India
| | - Anshit Singh
- Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra, India
| | - Amita Ghadge
- Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra, India
| | - Shyam D Nair
- Tata Institute of Fundamental Research, Subject Board of Biology, Hyderabad, Telangana, India
| | - Mahendra S Sonawane
- Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra, India; Development and Aging (ARUMDA), Advanced Research Unit on Metabolism, Tata Institute of Fundamental Research, Hyderabad, Telangana, India.
| | - Ullas Kolthur-Seetharam
- Tata Institute of Fundamental Research, Subject Board of Biology, Hyderabad, Telangana, India; Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra, India; Development and Aging (ARUMDA), Advanced Research Unit on Metabolism, Tata Institute of Fundamental Research, Hyderabad, Telangana, India; Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, India.
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de Oliveira KM, Soares GM, da Silva Junior JA, Alves BL, Freitas IN, Bem KCP, Mousovich-Neto F, Ribeiro RA, Carneiro EM. Prolonged postweaning protein restriction induces gut dysbiosis and colonic dysfunction in male mice. Am J Physiol Endocrinol Metab 2025; 328:E599-E610. [PMID: 40019118 DOI: 10.1152/ajpendo.00229.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 07/30/2024] [Accepted: 02/24/2025] [Indexed: 03/01/2025]
Abstract
Insufficient or imbalanced protein can disrupt gut microbiota, potentially compromising gut barrier function and increasing health risks. Herein, we investigated the effects of protein restriction on cecal microbiota and colon morphofunction in male mice. From 30 to 120 days of age, C57Bl/6 mice were fed a control protein diet [14% protein, control (C) group] or a low-protein diet [6% protein, protein-restricted (R) group]. At the end of the experimental period, R mice exhibited typical features of undernutrition, such as reduced body weight, hypoalbuminemia, and hypoproteinemia. In addition, despite the hyperphagia displayed in the R group, these mice presented a decreased amount of excreted feces and less energy content in feces. Cecal microbiota analysis demonstrated that protein restriction led to reductions in Shannon and Simpson indices and, therefore, dysbiosis. This effect was accompanied by morphological modifications in the proximal colon of R mice, such as 1) reduction in the total area of neurons of myenteric plexus; 2) increased number of goblet cells, with mucin droplets less developed; 3) reductions in crypt depth and diameter; 4) decreases in gene expressions for mucins and in the tight junction proteins expression; 5) enhanced paracellular permeability and expression of pro-inflammatory cytokines (tumor necrosis factor α, toll-like receptor 4, interferon γ, interleukin 1β, and interleukin 6), decreased anti-inflammatory cytokines (interleukins 4 and 10) in the colon, and increased plasma LPS binding protein concentrations. Therefore, protein restriction induced gut dysbiosis and may result in structural and functional negative impacts on the proximal colon barrier against luminal bacteria.NEW & NOTEWORTHY Prolonged postweaning protein restriction induced gut dysbiosis and led to a reduced neuron area in the myenteric plexus, with increased but underdeveloped goblet cells. Protein restriction decreased colonic crypt depth and diameter, and increased paracellular permeability due to lower expression of mucin-related genes and tight junction proteins. The diminished barrier function resulted in systemic inflammation, evidenced by elevated plasma LPS-binding protein and pro-inflammatory markers in the colon.
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Affiliation(s)
- Kênia Moreno de Oliveira
- Obesity and Comorbidities Research Center, Institute of Biology, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil
| | - Gabriela Moreira Soares
- Obesity and Comorbidities Research Center, Institute of Biology, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil
| | - Joel Alves da Silva Junior
- Obesity and Comorbidities Research Center, Institute of Biology, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil
| | - Bruna Lourençoni Alves
- Obesity and Comorbidities Research Center, Institute of Biology, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil
| | - Israelle Netto Freitas
- Obesity and Comorbidities Research Center, Institute of Biology, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil
| | - Kelly Cristina Pereira Bem
- Obesity and Comorbidities Research Center, Institute of Biology, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil
| | - Felippe Mousovich-Neto
- Departments of Pediatrics, Cell and Developmental Biology, Drukier Institute for Children's Health and Meyer Cancer Center, Weill Cornell Medicine, New York, New York, United States
| | - Rosane Aparecida Ribeiro
- Departamento de Biologia Geral, Setor de Ciências Biológicas e da Saúde, Universidade Estadual de Ponta Grossa (UEPG), Ponta Grossa, Brazil
| | - Everardo Magalhães Carneiro
- Obesity and Comorbidities Research Center, Institute of Biology, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil
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Olotu T, Ferrell JM. Lactobacillus sp. for the Attenuation of Metabolic Dysfunction-Associated Steatotic Liver Disease in Mice. Microorganisms 2024; 12:2488. [PMID: 39770690 PMCID: PMC11728176 DOI: 10.3390/microorganisms12122488] [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: 09/20/2024] [Revised: 11/19/2024] [Accepted: 11/26/2024] [Indexed: 01/05/2025] Open
Abstract
Probiotics are studied for their therapeutic potential in the treatment of several diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). Part of the significant progress made in understanding the pathogenesis of steatosis has come from identifying the complex interplay between the gut microbiome and liver function. Recently, probiotics have shown beneficial effects for the treatment and prevention of steatosis and MASLD in rodent models and in clinical trials. Numerous studies have demonstrated the promising potential of lactic acid bacteria, especially the genus Lactobacillus. Lactobacillus is a prominent bile acid hydrolase bacterium that is involved in the biotransformation of bile acids. This genus' modulation of the gut microbiota also contributes to overall gut health; it controls gut microbial overgrowth, shapes the intestinal bile acid pool, and alleviates inflammation. This narrative review offers a comprehensive summary of the potential of Lactobacillus in the gut-liver axis to attenuate steatosis and MASLD. It also highlights the roles of Lactobacillus in hepatic lipid metabolism, insulin resistance, inflammation and fibrosis, and bile acid synthesis in attenuating MASLD.
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Affiliation(s)
- Titilayo Olotu
- Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA;
- School of Biomedical Sciences, Kent State University, Kent, OH 44242, USA
| | - Jessica M. Ferrell
- Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA;
- School of Biomedical Sciences, Kent State University, Kent, OH 44242, USA
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Liu Z, Gonzalez-Nahm S, Zhang G, Dorsey A, Sela DA. Nutrition and the Gut Microbiome: Insights into New Dietary Strategies for Health. Nutr Health 2023:307-322. [DOI: 10.1007/978-3-031-24663-0_25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Radhakrishnan V, Lagudu PBB, Gangopadhyay D, Vijaykumar V, Rajaraman S, Perumal Kalaiyarasi J, Ganesan P, Ganesan TS. Neutropenic versus regular diet for acute leukaemia induction chemotherapy: randomised controlled trial. BMJ Support Palliat Care 2022; 12:421-430. [PMID: 35803707 DOI: 10.1136/spcare-2022-003833] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 06/24/2022] [Indexed: 11/04/2022]
Abstract
OBJECTIVES Restriction of raw fruits and vegetables (neutropenic diet) is advised for patients receiving treatment for acute leukaemia in low-income and middle-income countries (LMICs) to reduce infections despite evidence to the contrary from high-income countries. We, therefore, conducted a randomised controlled trial to ascertain the efficacy of the neutropenic diet in an LMIC setting. METHODS Patients aged 1-60 years receiving induction chemotherapy for acute leukaemia were randomised to a regular or neutropenic diet. The study's primary objective was to compare the incidence of major infections among patients receiving the two diets during induction chemotherapy. The secondary objectives were to compare stool microbial flora and induction mortality rates. RESULTS We randomised 200 patients, 98 patients to the regular diet arm and 102 to the neutropenic diet arm. Major infections occurred in 32 (32%) patients in the regular diet arm and 26 (25%) patients in the neutropenic diet arm (p=0.26). There were no statistically significant differences between patients receiving a regular diet versus neutropenic diet for blood culture positivity (n=6 vs 9), inotropic support (17 vs 12), mechanical ventilation (8 vs 5), third-line antibiotic use (28 vs 20), minor infections (12 vs 9), induction mortality (9 vs 4) and remission status (94% vs 94%). The stool culture on day 15 of induction grew multidrug-resistant bacteria in 38% of patients in the regular diet arm and 35% in the neutropenic diet arm (p=0.67). CONCLUSIONS A neutropenic diet did not prevent infections, reduce mortality or change stool microbial flora in patients with acute leukaemia.
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Affiliation(s)
| | | | | | | | - Swaminathan Rajaraman
- Epidemiology, Biostatistics and Cancer Registry, Cancer Institute-WIA, Chennai, Tamil Nadu, India
| | | | - Prasanth Ganesan
- Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education, Puducherry, India
| | - Trivadi S Ganesan
- Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, India
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Tihăuan BM, Axinie (Bucos) M, Marinaș IC, Avram I, Nicoară AC, Grădișteanu-Pîrcălăbioru G, Dolete G, Ivanof AM, Onisei T, Cășărică A, Pîrvu L. Evaluation of the Putative Duplicity Effect of Novel Nutraceuticals Using Physico-Chemical and Biological In Vitro Models. Foods 2022; 11:foods11111636. [PMID: 35681386 PMCID: PMC9180833 DOI: 10.3390/foods11111636] [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: 04/27/2022] [Revised: 05/28/2022] [Accepted: 05/30/2022] [Indexed: 12/12/2022] Open
Abstract
Nutraceuticals are experiencing a high-rise use nowadays, which is incomparable to a few years ago, due to a shift in consumers’ peculiarity tendencies regarding the selection of alternatives to Western medicine, potential immunity boosters, or gut-health promoters. Nutraceuticals’ compositions and actual effects should be proportional to their sought-after status, as they are perceived to be the middle ground between pharma rigor and naturally occurring actives. Therefore, the health benefits via nutrition, safe use, and reduction of potential harm should be the main focus for manufacturers. In this light, this study assess the nutritional profile (proteins, fats, fibers, caloric value, minerals) of a novel formulated nutraceutical, its physico-chemical properties, FTIR spectra, antioxidant activity, anthocyanins content, and potential hazards (heavy metals and microbiological contaminants), as well as its cytotoxicity, adherence, and invasion of bacteria on HT-29 cells, as well as its evaluation of beneficial effect, potential prebiotic value, and duplicity effect on gut microbiota in correlation with Regulation (EC) No 1924/2006. The results obtained indicate the growth stimulation of Lb. rhamnosus and the inhibitory effects of E.coli, Ent. Faecalis and Lc. lactis. The interaction between active compounds suggested a modulator effect of the intestinal microbiota by reducing the number of bacteria that adhere to epithelial cells or by inhibiting their growth.
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Affiliation(s)
- Bianca-Maria Tihăuan
- Life, Environmental and Earth Sciences Division, Research Institute of the University of Bucharest, 050096 Bucharest, Romania; (B.-M.T.); (I.-C.M.); (G.G.-P.); (A.-M.I.)
- Research & Development for Advanced Biotechnologies and Medical Devices, SC Sanimed International Impex SRL, 087040 Călugăreni, Romania
| | - Mădălina Axinie (Bucos)
- Research & Development for Advanced Biotechnologies and Medical Devices, SC Sanimed International Impex SRL, 087040 Călugăreni, Romania
- Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 011061 Bucharest, Romania;
- Correspondence:
| | - Ioana-Cristina Marinaș
- Life, Environmental and Earth Sciences Division, Research Institute of the University of Bucharest, 050096 Bucharest, Romania; (B.-M.T.); (I.-C.M.); (G.G.-P.); (A.-M.I.)
- Research & Development for Advanced Biotechnologies and Medical Devices, SC Sanimed International Impex SRL, 087040 Călugăreni, Romania
| | - Ionela Avram
- Department of Genetics, Faculty of Biology, University of Bucharest, 030018 Bucharest, Romania;
| | - Anca-Cecilia Nicoară
- Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, 020021 Bucharest, Romania;
| | - Grațiela Grădișteanu-Pîrcălăbioru
- Life, Environmental and Earth Sciences Division, Research Institute of the University of Bucharest, 050096 Bucharest, Romania; (B.-M.T.); (I.-C.M.); (G.G.-P.); (A.-M.I.)
- Research & Development for Advanced Biotechnologies and Medical Devices, SC Sanimed International Impex SRL, 087040 Călugăreni, Romania
- Academy of Romanian Scientists, 010071 Bucharest, Romania
| | - Georgiana Dolete
- Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 011061 Bucharest, Romania;
- National Research Center for Food Safety, University Politehnica of Bucharest, 060042 Bucharest, Romania
| | - Ana-Maria Ivanof
- Life, Environmental and Earth Sciences Division, Research Institute of the University of Bucharest, 050096 Bucharest, Romania; (B.-M.T.); (I.-C.M.); (G.G.-P.); (A.-M.I.)
- Research & Development for Advanced Biotechnologies and Medical Devices, SC Sanimed International Impex SRL, 087040 Călugăreni, Romania
| | - Tatiana Onisei
- National Institute of Research & Development for Food Bioresources—IBA Bucharest, 020323 Bucharest, Romania;
| | - Angela Cășărică
- National Institute for Chemical-Pharmaceutical Research and Development, 031282 Bucharest, Romania; (A.C.); (L.P.)
| | - Lucia Pîrvu
- National Institute for Chemical-Pharmaceutical Research and Development, 031282 Bucharest, Romania; (A.C.); (L.P.)
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Liatsos C, Papaefthymiou A, Kyriakos N, Galanopoulos M, Doulberis M, Giakoumis M, Petridou E, Mavrogiannis C, Rokkas T, Kountouras J. Helicobacter pylori, gastric microbiota and gastric cancer relationship: Unrolling the tangle. World J Gastrointest Oncol 2022; 14:959-972. [PMID: 35646287 PMCID: PMC9124990 DOI: 10.4251/wjgo.v14.i5.959] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/12/2021] [Accepted: 04/09/2022] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori infection (Hp-I) represents a typical microbial agent intervening in the complex mechanisms of gastric homeostasis by disturbing the balance between the host gastric microbiota and mucosa-related factors, leading to inflammatory changes, dysbiosis and eventually gastric cancer. The normal gastric microbiota shows diversity, with Proteobacteria [Helicobacter pylori (H. pylori) belongs to this family], Firmicutes, Actinobacteria, Bacteroides and Fusobacteria being the most abundant phyla. Most studies indicate that H. pylori has inhibitory effects on the colonization of other bacteria, harboring a lower diversity of them in the stomach. When comparing the healthy with the diseased stomach, there is a change in the composition of the gastric microbiome with increasing abundance of H. pylori (where present) in the gastritis stage, while as the gastric carcinogenesis cascade progresses to gastric cancer, the oral and intestinal-type pathogenic microbial strains predominate. Hp-I creates a premalignant environment of atrophy and intestinal metaplasia and the subsequent alteration in gastric microbiota seems to play a crucial role in gastric tumorigenesis itself. Successful H. pylori eradication is suggested to restore gastric microbiota, at least in primary stages. It is more than clear that Hp-I, gastric microbiota and gastric cancer constitute a challenging tangle and the strong interaction between them makes it difficult to unroll. Future studies are considered of crucial importance to test the complex interaction on the modulation of the gastric microbiota by H. pylori as well as on the relationships between the gastric microbiota and gastric carcinogenesis.
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Affiliation(s)
- Christos Liatsos
- Department of Gastroenterology, 401 General Military Hospital of Athens, Athens 11525, Greece
| | - Apostolis Papaefthymiou
- Department of Gastroenterology, 401 General Military Hospital of Athens, Athens 11525, Greece
- Gastroenterology, University Hospital of Larissa, Larissa 41336, Greece
| | - Nikolaos Kyriakos
- Department of Gastroenterology, 401 General Military Hospital of Athens, Athens 11525, Greece
| | - Michail Galanopoulos
- Department of Gastroenterology, 401 General Military Hospital of Athens, Athens 11525, Greece
| | - Michael Doulberis
- Division of Gastroenterology and Hepatology, Medical University Department, Kantonsspital Aarau, Aarau 1234, Switzerland
| | - Marios Giakoumis
- Department of Gastroenterology, 401 General Military Hospital of Athens, Athens 11525, Greece
| | - Evangelia Petridou
- Department of Microbiology, “Agia Sofia” Paediatric Hospital, Goudi, Athens 11527, Greece
| | - Christos Mavrogiannis
- Gastrointestinal and Liver Unit, Faculty of Nursing, Kifissia General and Oncology Hospital, Kaliftaki, N.Kifisia 14564, Greece
| | - Theodore Rokkas
- Gastroenterological Clinic, Henry Dunant Hospital, Athens 11525, Greece
| | - Jannis Kountouras
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki 41336, Macedonia, Greece
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Fathima S, Shanmugasundaram R, Adams D, Selvaraj RK. Gastrointestinal Microbiota and Their Manipulation for Improved Growth and Performance in Chickens. Foods 2022; 11:1401. [PMID: 35626971 PMCID: PMC9140538 DOI: 10.3390/foods11101401] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 05/01/2022] [Accepted: 05/09/2022] [Indexed: 12/17/2022] Open
Abstract
The gut of warm-blooded animals is colonized by microbes possibly constituting at least 100 times more genetic material of microbial cells than that of the somatic cells of the host. These microbes have a profound effect on several physiological functions ranging from energy metabolism to the immune response of the host, particularly those associated with the gut immune system. The gut of a newly hatched chick is typically sterile but is rapidly colonized by microbes in the environment, undergoing cycles of development. Several factors such as diet, region of the gastrointestinal tract, housing, environment, and genetics can influence the microbial composition of an individual bird and can confer a distinctive microbiome signature to the individual bird. The microbial composition can be modified by the supplementation of probiotics, prebiotics, or synbiotics. Supplementing these additives can prevent dysbiosis caused by stress factors such as infection, heat stress, and toxins that cause dysbiosis. The mechanism of action and beneficial effects of probiotics vary depending on the strains used. However, it is difficult to establish a relationship between the gut microbiome and host health and productivity due to high variability between flocks due to environmental, nutritional, and host factors. This review compiles information on the gut microbiota, dysbiosis, and additives such as probiotics, postbiotics, prebiotics, and synbiotics, which are capable of modifying gut microbiota and elaborates on the interaction of these additives with chicken gut commensals, immune system, and their consequent effects on health and productivity. Factors to be considered and the unexplored potential of genetic engineering of poultry probiotics in addressing public health concerns and zoonosis associated with the poultry industry are discussed.
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Affiliation(s)
- Shahna Fathima
- Department of Poultry Science, The University of Georgia, Athens, GA 30605, USA; (S.F.); (D.A.); (R.K.S.)
| | - Revathi Shanmugasundaram
- Toxicology and Mycotoxin Research Unit, US National Poultry Research Center, Athens, GA 30605, USA
| | - Daniel Adams
- Department of Poultry Science, The University of Georgia, Athens, GA 30605, USA; (S.F.); (D.A.); (R.K.S.)
| | - Ramesh K. Selvaraj
- Department of Poultry Science, The University of Georgia, Athens, GA 30605, USA; (S.F.); (D.A.); (R.K.S.)
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Zapanta K, Schroeder ET, Fisher BE. Rethinking Parkinson Disease: Exploring Gut-Brain Interactions and the Potential Role of Exercise. Phys Ther 2022; 102:6535135. [PMID: 35225349 DOI: 10.1093/ptj/pzac022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 11/09/2021] [Accepted: 02/21/2022] [Indexed: 12/21/2022]
Abstract
UNLABELLED Although Parkinson disease (PD) has traditionally been considered a disease of the central nervous system, a bidirectional communication system known as the gut-brain axis can influence PD pathogenesis. The dual-hit hypothesis proposed that PD is due to peripheral dysregulations to the gut microbiota, known as dysbiosis. Since then, further investigation has shown that there are multiple pathological sources associated with PD. However, dysbiosis plays a critical role in the disease process. Substantial evidence has identified that cardinal motor symptoms of PD and disease progression are associated with dysbiosis. In other neurodegenerative disorders, dysbiosis has been linked to cognition. Non-PD research has shown that exercise can effectively restore the gut microbiota. Likewise, exercise has become a well-established strategy to improve cognitive and motor function in PD. However, despite the interaction between the gut and brain, and the exercise benefits on gut health, no research to date has considered the effects of exercise on the gut microbiota in PD. Therefore, the purpose of this Perspective is to explore whether exercise benefits observed in PD could partly be due to restorations to the gut microbiota. First, we will review the gut-brain axis and its influence on motor and cognitive function. Next, we will outline evidence regarding exercise-induced restoration of the gut microbiota in non-PD populations. Finally, we will summarize benefits of exercise on motor-cognitive function in PD, proposing that benefits of exercise seen in PD might actually be due to restorations to the gut microbiota. By positing the gut microbiota as a moderator of exercise improvements to motor and cognitive function, we aim to provide a new perspective for physical therapists to prioritize exercise regimens for individuals with PD that can specifically restore the gut microbiota to better improve PD symptoms and prognosis. IMPACT This Perspective raises awareness that dysregulations to the gut microbiota have recently been attributed to PD symptoms and pathology and that exercise can be an effective therapeutic strategy to improve gut health in individuals with PD. LAY SUMMARY People with PD have been found to have reduced microbial diversity in their gut, which can play an important role in the progression of the disease. Physical therapists can design therapeutic exercises that might help improve gut health in people with PD.
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Affiliation(s)
- Kaylie Zapanta
- Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, California, USA
| | - E Todd Schroeder
- Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, California, USA
| | - Beth E Fisher
- Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, California, USA.,Department of Neurology, University of Southern California, Los Angeles, California, USA
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Roles of Microbiota in Cancer: From Tumor Development to Treatment. JOURNAL OF ONCOLOGY 2022; 2022:3845104. [PMID: 35342407 PMCID: PMC8941494 DOI: 10.1155/2022/3845104] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 02/24/2022] [Accepted: 03/01/2022] [Indexed: 12/11/2022]
Abstract
Cancer as a second leading cause of death arises from multifactorial pathology. The association of microbiota and their products with various pathologic conditions including cancer is receiving significant attention over the past few years. Mounting evidence showed that human microbiota is an emerging target in tumor onset, progression, prevention, and even diagnosis. Accordingly, modulating this composition might influence the response to tumor therapy and therapeutic resistance as well. Through this review, one could conceive of complex interaction between the microbiome and cancer in either positive or negative manner by which may hold potential for finding novel preventive and therapeutic strategies against cancer.
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Meliț LE, Mărginean CO, Săsăran MO. The Yin-Yang Concept of Pediatric Obesity and Gut Microbiota. Biomedicines 2022; 10:biomedicines10030645. [PMID: 35327446 PMCID: PMC8945275 DOI: 10.3390/biomedicines10030645] [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: 02/07/2022] [Revised: 03/05/2022] [Accepted: 03/07/2022] [Indexed: 02/04/2023] Open
Abstract
The era of pediatric obesity is no longer a myth. Unfortunately, pediatric obesity has reached alarming incidence levels worldwide and the factors that contribute to its development have been intensely studied in multiple recent and emerging studies. Gut microbiota was recently included in the wide spectrum of factors implicated in the determination of obesity, but its role in pediatric obese patients is far from being fully understood. In terms of the infant gut microbiome, multiple factors have been demonstrated to shape its content, including maternal diet and health, type of delivery, feeding patterns, weaning and dietary habits. Nevertheless, the role of the intrauterine environment, such as the placental microbial community, cannot be completely excluded. Most studies have identified Firmicutes and Bacteroidetes as the most important players related to obesity risk in gut microbiota reflecting an increase of Firmicutes and a decrease in Bacteroidetes in the context of obesity; however, multiple inconsistencies between studies were recently reported, especially in pediatric populations, and there is a scarcity of studies performed in this age group.
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Affiliation(s)
- Lorena Elena Meliț
- Department of Pediatrics I, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No 38, 540136 Târgu Mureș, Romania;
| | - Cristina Oana Mărginean
- Department of Pediatrics I, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No 38, 540136 Târgu Mureș, Romania;
- Correspondence:
| | - Maria Oana Săsăran
- Department of Pediatrics III, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No 38, 540136 Târgu Mureș, Romania;
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12
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Barnett JA, Bandy ML, Gibson DL. Is the Use of Glyphosate in Modern Agriculture Resulting in Increased Neuropsychiatric Conditions Through Modulation of the Gut-brain-microbiome Axis? Front Nutr 2022; 9:827384. [PMID: 35356729 PMCID: PMC8959108 DOI: 10.3389/fnut.2022.827384] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 01/24/2022] [Indexed: 11/13/2022] Open
Abstract
Environmental exposure to glyphosate and glyphosate-based herbicides has the potential to negatively influence neurodevelopment and behavior across generations indirectly through the gut-brain-microbiome axis. Potential mechanisms by which glyphosate may elicit these effects are through the disruption of the normally symbiotic relationship of the host and the gut microbiome. Given glyphosate can kill commensal members of the microbiome like Lactobacillus spp., Ruminococaeae and Butyricoccus spp., resulting in reductions in key microbial metabolites that act through the gut-brain-microbiome axis including indoles, L-glutamate and SCFAs. Glyphosate- resistant microbes in the gut have the potential to increase the production of pro-inflammatory cytokines and reactive oxygen species which may result in increased HPA activation, resulting in increased production of glucocorticoids which have implications on neurodevelopment. In addition, maternal transfer of the gut microbiome can affect immune and neurodevelopment, across generations. This perspective article weighs the evidence for chronic glyphosate exposure on the gut microbiome and the potential consequences on the gut-brain axis correlated with increased incidence of neuropsychiatric conditions.
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Affiliation(s)
| | - Maya L. Bandy
- Department of Biology, The University of British Columbia, Kelowna, BC, Canada
| | - Deanna L. Gibson
- Department of Biology, The University of British Columbia, Kelowna, BC, Canada
- Department of Medicine, Faculty of Medicine, The University of British Columbia, Kelowna, BC, Canada
- *Correspondence: Deanna L. Gibson
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13
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Could Dietary Supplementation with Different Sources of N-3 Polyunsaturated Fatty Acids Modify the Rabbit Gut Microbiota? Antibiotics (Basel) 2022; 11:antibiotics11020227. [PMID: 35203829 PMCID: PMC8868100 DOI: 10.3390/antibiotics11020227] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/05/2022] [Accepted: 02/08/2022] [Indexed: 11/22/2022] Open
Abstract
The present study evaluated the effects of feed supplemented with two dietary sources of n-3 polyunsaturated fatty acids (PUFAs; fish oil and extruded flaxseed) on the gut microbiota, caecal fermentations, gastrointestinal histology, and histochemistry in rabbits. Fifteen male New Zealand White rabbits were divided into three groups (n = 5/group) and fed with different diets from weaning (35 days of age) until slaughtering (90 days of age): C group, fed with a commercial diet; F group, supplemented with 10% of extruded flaxseed; and O group, supplemented with 3.5% of fish oil. At slaughter, the content of the stomach, duodenum, jejunum, ileum, caecum, and colon was collected and analyzed by Next Generation 16S rRNA gene sequencing. Tissue samples of the same tracts were evaluated with histological and histochemical analysis. Ammonia and lactic acid in the caecum were also quantified. Twenty-nine operational taxonomic units (OTUs) were significantly different between groups. Groups receiving n-3 PUFAs supplementation showed an increase in Bacteroidetes and Lachnospiraceae in several gastrointestinal tracts, while Bacilli abundance, as well as Firmicutes/Bacteroidetes ratio, were reduced compared to the control group (for all p < 0.05). Caecal ammonia was lower in the F than C group (p < 0.032), whereas no difference was found for lactic acid. Finally, histological evaluations revealed a mild hemorrhagic infiltration and vessels ectasia in the stomach mucosa of both F and O groups, but no effect of nutritional treatment was evidenced by the histochemical analyses. In conclusion, n-3 PUFAs supplementation could modify the rabbit gut microbiota and fermentation. The increase in beneficial bacterial populations may, at least partially, explain the positive effects of n-3 PUFAs diet supplementation on human and animals’ health, although the appropriate dosage should be established.
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Aruwa CE, Pillay C, Nyaga MM, Sabiu S. Poultry gut health - microbiome functions, environmental impacts, microbiome engineering and advancements in characterization technologies. J Anim Sci Biotechnol 2021; 12:119. [PMID: 34857055 PMCID: PMC8638651 DOI: 10.1186/s40104-021-00640-9] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 10/01/2021] [Indexed: 12/12/2022] Open
Abstract
The gastrointestinal tract (GIT) health impacts animal productivity. The poultry microbiome has functions which range from protection against pathogens and nutrients production, to host immune system maturation. Fluctuations in the microbiome have also been linked to prevailing environmental conditions. Healthy poultry birds possess a natural resistance to infection. However, the exploration of environmental impacts and other relevant factors on poultry growth and health have been underplayed. Since good performance and growth rate are central to animal production, the host-microbiome relationship remains integral. Prior to the emergence of metagenomic techniques, conventional methods for poultry microbiome studies were used and were low-throughput and associated with insufficient genomic data and high cost of sequencing. Fortunately, the advent of high-throughput sequencing platforms have circumvented some of these shortfalls and paved the way for increased studies on the poultry gut microbiome diversity and functions. Here, we give an up-to-date review on the impact of varied environments on microbiome profile, as well as microbiome engineering and microbiome technology advancements. It is hoped that this paper will provide invaluable information that could guide and inspire further studies on the lingering pertinent questions about the poultry microbiome.
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Affiliation(s)
- Christiana Eleojo Aruwa
- Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, P.O. Box 1334, Durban, 4000, South Africa
| | - Charlene Pillay
- Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, P.O. Box 1334, Durban, 4000, South Africa
| | - Martin M Nyaga
- Next Generation Sequencing Unit, Division of Virology, Faculty of Heath Sciences, University of the Free State, Bloemfontein, South Africa
| | - Saheed Sabiu
- Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, P.O. Box 1334, Durban, 4000, South Africa.
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15
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Ringenier M, Caekebeke N, De Meyer F, Van Limbergen T, Eeckhaut V, Ducatelle R, Van Immerseel F, Dewulf J. A field study on correlations between macroscopic gut health scoring, histological measurements and performance parameters in broilers. Avian Pathol 2021; 50:500-506. [PMID: 34463594 DOI: 10.1080/03079457.2021.1973960] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Optimal intestinal health is a prerequisite for sustainable poultry production. Intestinal health can be evaluated by scoring macroscopic intestinal abnormalities and by histological measurements. The aim of this study was to evaluate correlations between macroscopic gut appearance scoring (GAS), coccidiosis lesion scoring, histological measurements and performance parameters in broilers under field conditions. Therefore, a cross-sectional study was performed on 50 broiler farms where birds were sampled at 28 days of age. The GAS was determined by scoring the absence or presence of 10 macroscopically visible parameters of the gastrointestinal tract, yielding a GAS between 0 and 10, with 0 meaning no gut abnormalities. On individual bird level, when birds had a GAS score of 6 or higher, significantly shorter villi were found in the duodenum. Also, CD3+ T-lymphocyte area percentage in the duodenal mucosa was significantly negatively correlated to villus length. On farm level, the average feed conversion ratio (FCR) was 1.59 ± 0.04 [1.52-1.73]. However, no correlations were found between the GAS at the age of 28 days and the prevalence of coccidiosis, nor did coccidiosis lesion scoring correlate with the FCR. Also, a higher GAS could not be associated with a higher FCR. In conclusion, on all farms a certain degree of macroscopic visible gut and coccidiosis lesions were present in birds of 28 days of age, while this did not correlate with the FCR. This suggests that broilers are able to cope with a certain level of gut damage before it influences the overall performance.
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Affiliation(s)
- M Ringenier
- Department of Reproduction, Obstetrics and Herd Health, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium
| | - N Caekebeke
- Department of Reproduction, Obstetrics and Herd Health, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium
| | - F De Meyer
- Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium
| | | | - V Eeckhaut
- Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium
| | - R Ducatelle
- Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium
| | - F Van Immerseel
- Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium
| | - J Dewulf
- Department of Reproduction, Obstetrics and Herd Health, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium
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Martínez JE, Vargas A, Pérez-Sánchez T, Encío IJ, Cabello-Olmo M, Barajas M. Human Microbiota Network: Unveiling Potential Crosstalk between the Different Microbiota Ecosystems and Their Role in Health and Disease. Nutrients 2021; 13:2905. [PMID: 34578783 PMCID: PMC8466470 DOI: 10.3390/nu13092905] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 08/19/2021] [Accepted: 08/20/2021] [Indexed: 12/13/2022] Open
Abstract
The human body is host to a large number of microorganisms which conform the human microbiota, that is known to play an important role in health and disease. Although most of the microorganisms that coexist with us are located in the gut, microbial cells present in other locations (like skin, respiratory tract, genitourinary tract, and the vaginal zone in women) also play a significant role regulating host health. The fact that there are different kinds of microbiota in different body areas does not mean they are independent. It is plausible that connection exist, and different studies have shown that the microbiota present in different zones of the human body has the capability of communicating through secondary metabolites. In this sense, dysbiosis in one body compartment may negatively affect distal areas and contribute to the development of diseases. Accordingly, it could be hypothesized that the whole set of microbial cells that inhabit the human body form a system, and the dialogue between the different host microbiotas may be a contributing factor for the susceptibility to developing diseased states. For this reason, the present review aims to integrate the available literature on the relationship between the different human microbiotas and understand how changes in the microbiota in one body region can influence other microbiota communities in a bidirectional process. The findings suggest that the different microbiotas may act in a coordinated way to decisively influence human well-being. This new integrative paradigm opens new insights in the microbiota field of research and its relationship with human health that should be taken into account in future studies.
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Affiliation(s)
| | | | | | | | - Miriam Cabello-Olmo
- Biochemistry Area, Department of Health Science, Public University of Navarre, 31008 Pamplona, Spain; (J.E.M.); (A.V.); (T.P.-S.); (I.J.E.)
| | - Miguel Barajas
- Biochemistry Area, Department of Health Science, Public University of Navarre, 31008 Pamplona, Spain; (J.E.M.); (A.V.); (T.P.-S.); (I.J.E.)
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17
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The Link between Obesity, Microbiota Dysbiosis, and Neurodegenerative Pathogenesis. Diseases 2021; 9:diseases9030045. [PMID: 34201465 PMCID: PMC8293145 DOI: 10.3390/diseases9030045] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 06/19/2021] [Accepted: 06/21/2021] [Indexed: 02/07/2023] Open
Abstract
Current research in medicine in several parts of the world has attempted to establish a link between the occurrence of neurodegenerative pathologies, microbiota dysbiosis, and the incidence of obesity. The body’s response to different physicochemical factors has also been influenced by the proper assimilation of bioactive compounds contained in the food that is ingested. Oxidative stress is one of the major factors that directly affects the functioning of the human microbiota. The body’s reaction to this imbalance is crucial to the progression of inflammatory processes, which are based on molecular mechanisms. Microbial dysbiosis can result in a possibly permanent alteration in the physiological response. This review aims to highlight recent contributions made to alleviating human dysbiosis in degenerative diseases, especially for neurodegenerative pathologies based on the rising prevalence of obesity. We discuss the significance of both microbiota modulation and possible alleviations of pathologies by a modulatory function. We argue that pre- and probiotics (including phenolic compounds stimulating the favorable strain from the microbiota) are an effective alternative that can support the microbiota pattern’s modulation over time and the attenuation of indirect causes that determine dysbiosis. Molecular aspects are presented in support of the modulating role of the microbiota following the use of probiotics.
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18
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Nutritional and therapeutic approaches for protecting human gut microbiota from psychotropic treatments. Prog Neuropsychopharmacol Biol Psychiatry 2021; 108:110182. [PMID: 33232785 DOI: 10.1016/j.pnpbp.2020.110182] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 11/05/2020] [Accepted: 11/16/2020] [Indexed: 02/07/2023]
Abstract
Emerging evidence highlighted the essential role played by the microbiota-gut-brain axis in maintaining human homeostasis, including nutrition, immunity, and metabolism. Much recent work has linked the gut microbiota to many psychiatric and neurodegenerative disorders such as depression, schizophrenia, and Alzheimer's disease. Shared gut microbiota alterations or dysbiotic microbiota have been identified in these separate disorders relative to controls. Much attention has focused on the bidirectional interplay between the gut microbiota and the brain, establishing gut dysbiotic status as a critical factor in psychiatric disorders. Still, the antibiotic-like effect of psychotropic drugs, medications used for the treatment of these disorders, on gut microbiota is largely neglected. In this review, we summarize the current findings on the impact of psychotropics on gut microbiota and how their antimicrobial potency can trigger dysbiosis. We also discuss the potential therapeutic strategies, including probiotics, prebiotics, and fecal transplantation, to attenuate the dysbiosis related to psychotropics intake.
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19
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Vander Wyst KB, Ortega-Santos CP, Toffoli SN, Lahti CE, Whisner CM. Diet, adiposity, and the gut microbiota from infancy to adolescence: A systematic review. Obes Rev 2021; 22:e13175. [PMID: 33590719 PMCID: PMC10762698 DOI: 10.1111/obr.13175] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 10/30/2020] [Accepted: 10/31/2020] [Indexed: 12/14/2022]
Abstract
Early life gut microbiota are affected by several factors that make identification of microbial-adiposity relationships challenging. This review evaluates studies that have investigated the gut microbiota composition associated with adiposity in infants, children, and adolescents and provides evidence-based nutrition recommendations that address microbiota-adiposity links. Electronic databases were systematically searched through January 2020. Eligible studies were published in English and analyzed gut microbiota and adiposity among individuals aged birth to 18 years. Abstracts and full-text articles were reviewed by three independent reviewers. Of 45 full-text articles reviewed, 33 were included. No difference in abundance was found for Bacteroidetes (n = 7/15 articles), Firmicutes (n = 10/17), Actinobacteria (n = 8/12), Proteobacteria (n = 8/12), Tenericutes (n = 4/5), and Verrucomicrobia (n = 4/6) with adiposity. Lower abundance of Christensenellaceae (n = 3/5) and Rikenellaceae (n = 6/8) but higher abundance of F. prausnitzii (n = 3/5) and Prevotella (n = 5/7) were associated with adiposity. A lack of consensus exists for gut microbial composition associations with adiposity. A healthy gut microbiota is associated with a diet rich in fruits and vegetables with moderate consumption of animal fat and protein. Future research should use more robust sequencing technologies to identify all bacterial taxa associated with adiposity and evaluate how diet effects these adiposity-associated microbes.
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Affiliation(s)
- Kiley B Vander Wyst
- College of Health Solutions, Arizona State University, Phoenix, Arizona, USA
- Center for Health Promotion and Disease Prevention, Arizona State University, Phoenix, Arizona, USA
| | | | - Samantha N Toffoli
- College of Health Solutions, Arizona State University, Phoenix, Arizona, USA
| | - Caroline E Lahti
- College of Liberal Arts and Sciences, Arizona State University, Phoenix, Arizona, USA
| | - Corrie M Whisner
- College of Health Solutions, Arizona State University, Phoenix, Arizona, USA
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Withrow D, Bowers SJ, Depner CM, González A, Reynolds AC, Wright KP. Sleep and Circadian Disruption and the Gut Microbiome-Possible Links to Dysregulated Metabolism. CURRENT OPINION IN ENDOCRINE AND METABOLIC RESEARCH 2021; 17:26-37. [PMID: 34805616 PMCID: PMC8597978 DOI: 10.1016/j.coemr.2020.11.009] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Insufficient sleep and circadian misalignment are associated with adverse metabolic health outcomes. Alterations in gut microbial diversity occur with insufficient sleep and circadian misalignment, which can lead to modifications in microbial structure and function. Changes in microbially produced and modified metabolites such as short chain fatty acids and secondary bile acids may contribute to chronic inflammation, positive energy balance and endocrine changes, and represent potential mechanisms linking insufficient sleep and circadian misalignment with metabolic dysregulation. Literature primarily from the last two years is reviewed here, examining the impact of sleep and circadian rhythms and their disruption on the gut microbiome in human and non-human models, with an emphasis on the hypothesis that the altered gut microbiome may be one pathway by which insufficient sleep and circadian misalignment dysregulate metabolism.
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Affiliation(s)
- Dana Withrow
- Sleep and Chronobiology Laboratory, Department of Integrative Physiology, University of Colorado-Boulder, Boulder, CO, USA
| | - Samuel J. Bowers
- Center for Sleep and Circadian Biology, Northwestern University, Evanston, IL, USA
| | - Christopher M. Depner
- Sleep and Chronobiology Laboratory, Department of Integrative Physiology, University of Colorado-Boulder, Boulder, CO, USA
- Department of Health and Kinesiology, University of Utah, Salt Lake City, UT, USA
| | - Antonio González
- Department of Pediatrics, University of California at San Diego, La Jolla, CA, USA
| | - Amy C. Reynolds
- The Appleton Institute, CQUniversity Australia, Adelaide, Australia
| | - Kenneth P. Wright
- Sleep and Chronobiology Laboratory, Department of Integrative Physiology, University of Colorado-Boulder, Boulder, CO, USA
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21
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Suneson K, Lindahl J, Chamli Hårsmar S, Söderberg G, Lindqvist D. Inflammatory Depression-Mechanisms and Non-Pharmacological Interventions. Int J Mol Sci 2021; 22:1640. [PMID: 33561973 PMCID: PMC7915869 DOI: 10.3390/ijms22041640] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 02/01/2021] [Accepted: 02/02/2021] [Indexed: 02/08/2023] Open
Abstract
Treatment of depression is hampered by the failure to identify distinct symptom profiles with distinct pathophysiologies that differentially respond to distinct treatments. We posit that inflammatory depression is a meaningful depression subtype associated with specific symptoms and biological abnormalities. We review several upstream, potentially causative, mechanisms driving low-grade inflammation in this subtype of depression. We also discuss downstream mechanisms mediating the link between inflammation and symptoms of depression, including alterations in dopaminergic neurotransmission and tryptophan metabolism. Finally, we review evidence for several non-pharmacological interventions for inflammatory depression, including probiotics, omega-3 fatty acids, and physical exercise interventions. While some evidence suggests that these interventions may be efficacious in inflammatory depression, future clinical trials should consider enriching patient populations for inflammatory markers, or stratify patients by inflammatory status, to confirm or refute this hypothesis.
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Affiliation(s)
- Klara Suneson
- Department of Clinical Sciences Lund, Psychiatry, Faculty of Medicine, Lund University, 221 85 Lund, Sweden; (J.L.); (G.S.); (D.L.)
- Office for Psychiatry and Habilitation, Psychiatric Clinic Helsingborg, Region Skåne, 252 23 Helsingborg, Sweden
| | - Jesper Lindahl
- Department of Clinical Sciences Lund, Psychiatry, Faculty of Medicine, Lund University, 221 85 Lund, Sweden; (J.L.); (G.S.); (D.L.)
- Office for Psychiatry and Habilitation, Psychiatric Clinic Lund, Region Skåne, 221 85 Lund, Sweden;
| | - Simon Chamli Hårsmar
- Office for Psychiatry and Habilitation, Psychiatric Clinic Lund, Region Skåne, 221 85 Lund, Sweden;
| | - Gustav Söderberg
- Department of Clinical Sciences Lund, Psychiatry, Faculty of Medicine, Lund University, 221 85 Lund, Sweden; (J.L.); (G.S.); (D.L.)
| | - Daniel Lindqvist
- Department of Clinical Sciences Lund, Psychiatry, Faculty of Medicine, Lund University, 221 85 Lund, Sweden; (J.L.); (G.S.); (D.L.)
- Office for Psychiatry and Habilitation, Psychiatry Research Skåne, Region Skåne, 221 85 Lund, Sweden
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Bajinka O, Tan Y, Abdelhalim KA, Özdemir G, Qiu X. Extrinsic factors influencing gut microbes, the immediate consequences and restoring eubiosis. AMB Express 2020; 10:130. [PMID: 32710186 PMCID: PMC7381537 DOI: 10.1186/s13568-020-01066-8] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Accepted: 07/18/2020] [Indexed: 02/07/2023] Open
Abstract
From the emerging studies, the more diverse the microbial population in the gut, the healthier the gut. Health benefits are associated with the functional characteristics of these diverse microbial genes. Extrinsic factors causing dysbiosis are extensively studied however, linking the varying degree of consequences to the respective factors and therapeutic possibilities are not explored at length. This review aims to examine from previous studies and put forward the types of dysbiosis, the immediate consequences and the scientific approaches to restore disrupted microbiota. Dietary supplements are found to be one of the factors contributing profoundly to the alteration of gut microbiota. While diet rich in fibre and fermented food established a diverse microbiome and produce vital metabolites, high fat, animal proteins and high caloric carbohydrate are as well relative to dysbiosis among infants, adult or diseases individuals. The intermittent fasting, feeding methods, the pH and water quality are among the factors associated with dysbiosis. Prebiotics and Probiotics maintain and restore gut homeostasis. Antibiotic-induced dysbiosis are relatively on the spectrum of activity, the pharmacokinetics properties, the dose taken during the treatment route of administration and the duration of drug therapy. The higher the altitude, the lesser the diversity. Extreme temperatures as well are related to reduced microbial activity and metabolism. Delivery through caserium-section deprived the newborn from restoring valuable vaginal bacterial species and the baby will instead assumed intestinal microbiota-like. While exercise and oxidative stress contribute even though moderately, fecal microbial transfer (FMT) also influence gut microbiota.
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Liu Y, Brown PN, Ragone D, Gibson DL, Murch SJ. Breadfruit flour is a healthy option for modern foods and food security. PLoS One 2020; 15:e0236300. [PMID: 32702056 PMCID: PMC7377419 DOI: 10.1371/journal.pone.0236300] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 07/01/2020] [Indexed: 11/18/2022] Open
Abstract
Breadfruit is a traditional staple crop from Pacific islands with the potential to improve worldwide food security and mitigate diabetes. Flour produced from breadfruit is a gluten-free, low glycemic index, nutrient dense and complete protein option for modern foods but basic scientific knowledge of health impacts of a breadfruit-based diet in animals and humans was lacking. We designed a series of studies to provide basic and fundamental data on impacts of a breadfruit-based diet through an in vitro and in vivo model. Cooked breadfruit flour was digested through a multi-stage enzyme digestion model to estimate protein digestibility in comparison to wheat flour. Breadfruit protein was found to be easier to digest than wheat protein in the enzyme digestion model. The flour digestions were applied to Caco-2 cells to test the cytotoxicity and to measure the immunogenicity through cytokine expression. No significant differences were observed for immune factors and cytokines (IL-4, IL-10, IL-8, TNF-α, IFN-γ) on Caco-2 cells between the breadfruit and wheat groups. A breadfruit-based rodent chow was formulated by substitution of all of the wheat in the standard formulation with breadfruit. The diets were isocaloric, nutrient equivalent and used to feed male and female C57BL/6 mice for 21 days. No sign of malnutrition, discomfort, illness or death was observed among the mice because of the diet. The histology and the cytokine expression of the mice ileum from both groups were analyzed and showed similar results. The expression of major bacteria was measured in the colon and showed similar results. Mice fed the breadfruit diet had a significantly higher growth rate and body weight than standard diet fed mice. No negative health outcomes were observed in studies with in vitro or in vivo models and breadfruit flour is a healthy alternative to other starches for modern foods.
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Affiliation(s)
- Ying Liu
- Chemistry, University of British Columbia, Kelowna, British Columbia, Canada
- Natural Health and Food Products Research Group, British Columbia Institute of Technology, Burnaby, British Columbia, Canada
| | - Paula N. Brown
- Natural Health and Food Products Research Group, British Columbia Institute of Technology, Burnaby, British Columbia, Canada
| | - Diane Ragone
- Breadfruit Institute, National Tropical Botanical Garden, Kauai, Hawaii, United States of America
| | - Deanna L. Gibson
- Biology, University of British Columbia, Kelowna, British Columbia, Canada
| | - Susan J. Murch
- Chemistry, University of British Columbia, Kelowna, British Columbia, Canada
- * E-mail:
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24
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Shang X, He X, Liu H, Wen B, Tan T, Xu C, Niu W, Zhang Y. Stachyose Prevents Intestinal Mucosal Injury in the Immunosuppressed Mice. STARCH-STARKE 2020. [DOI: 10.1002/star.201900073] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Affiliation(s)
- Xiaoya Shang
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences Northwestern Polytechnical University Xi'an Shaanxi 710072 China
| | - Xiaoqin He
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences Northwestern Polytechnical University Xi'an Shaanxi 710072 China
| | - Huan Liu
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences Northwestern Polytechnical University Xi'an Shaanxi 710072 China
| | - Bingjie Wen
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences Northwestern Polytechnical University Xi'an Shaanxi 710072 China
| | - Taicong Tan
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences Northwestern Polytechnical University Xi'an Shaanxi 710072 China
| | - Chunlan Xu
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences Northwestern Polytechnical University Xi'an Shaanxi 710072 China
| | - Weining Niu
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences Northwestern Polytechnical University Xi'an Shaanxi 710072 China
| | - Yong Zhang
- Department of Surgical Oncology the First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi 710061 China
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Singh A, Nayak N, Rathi P, Verma D, Sharma R, Chaudhary A, Agarwal A, Tripathi YB, Garg N. Microbiome and host crosstalk: A new paradigm to cancer therapy. Semin Cancer Biol 2020; 70:71-84. [PMID: 32479952 DOI: 10.1016/j.semcancer.2020.05.014] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 05/19/2020] [Accepted: 05/22/2020] [Indexed: 12/17/2022]
Abstract
The commensal microbiome of humans has co-evolved for thousands of years. The microbiome regulates human health and is also linked to several diseases, including cancer. The advances in next-generation sequencing have significantly contributed to our understanding of the microbiome and its association with cancer and cancer therapy. Recent studies have highlighted a close relationship of the microbiome to the pharmacological effect of chemotherapy and immunotherapy. The chemo-drugs usually interfere with the host immune system and reduces the microbiome diversity inside the body, which in turn leads to decreased efficacy of these drugs. The human microbiome, specifically the gut microbiome, increases the potency of chemo-drugs through metabolism, enzymatic degradation, ecological differences, and immunomodulation. Recent research exploits the involvement of microbiome to shape the efficacy and decrease the toxicity of these chemo-drugs. In this review, we have highlighted the recent development in understanding the relationship of the human microbiome with cancer and also emphasize on various roles of the microbiome in the modulation of cancer therapy. Additionally, we also summarize the ongoing research focussed on the improved efficacy of chemotherapy and immunotherapy using the host microbiome.
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Affiliation(s)
- Ashutosh Singh
- School of Basic Sciences, Indian Institute of Technology Mandi, Mandi 175005, Himachal Pradesh, India
| | - Namyashree Nayak
- School of Basic Sciences, Indian Institute of Technology Mandi, Mandi 175005, Himachal Pradesh, India
| | - Preeti Rathi
- School of Basic Sciences, Indian Institute of Technology Mandi, Mandi 175005, Himachal Pradesh, India
| | - Deepanshu Verma
- School of Basic Sciences, Indian Institute of Technology Mandi, Mandi 175005, Himachal Pradesh, India
| | - Rohit Sharma
- Department of Rasashastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, BHU, Varanasi 221005, Uttar Pradesh, India
| | - Ashun Chaudhary
- Central University of Himachal Pradesh, Shahpur, Dist. Kangra, Himachal Pradesh 176206, India
| | - Alka Agarwal
- Department of Medicinal Chemistry, Faculty of Ayurveda, Institute of Medical Sciences, BHU, Varanasi 221005, Uttar Pradesh, India
| | - Yamini Bhushan Tripathi
- Department of Medicinal Chemistry, Faculty of Ayurveda, Institute of Medical Sciences, BHU, Varanasi 221005, Uttar Pradesh, India
| | - Neha Garg
- Department of Medicinal Chemistry, Faculty of Ayurveda, Institute of Medical Sciences, BHU, Varanasi 221005, Uttar Pradesh, India.
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Talavera-Urquijo E, Beisani M, Balibrea JM, Alverdy JC. Is bariatric surgery resolving NAFLD via microbiota-mediated bile acid ratio reversal? A comprehensive review. Surg Obes Relat Dis 2020; 16:1361-1369. [PMID: 32336663 DOI: 10.1016/j.soard.2020.03.013] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Revised: 01/18/2020] [Accepted: 03/11/2020] [Indexed: 02/07/2023]
Abstract
Despite the fact that there is still insufficient evidence to consider non-alcoholic fatty liver disease (NAFLD) as an stand-alone indication for bariatric surgery, many clinical and histopathological beneficial effects on both NAFLD and non-alcoholic steatohepatitis (NASH) have been shown. Although weight loss seems to be the obvious mechanism, weight-loss independent factors are also believed to be involved. Among them, changes in gut microbiota and bile acids (BA) composition may be playing an unappreciated role in the improvement of NAFLD. In this review we examine the mechanisms and interdependence of the gut microbiota and BA, and their influence on NAFLD pathogenesis and its reversal following bariatric surgery. According to the currently available evidence, gut microbiota has a major influence on BA composition. In fact, both BA and microbiome disturbances (dysbiosis) play a role in the etiopathogenesis of NAFLD and might be potential therapeutic targets. In addition, bariatric surgery can modify the intraluminal ileal environment in a way that causes significant repopulation of the gut microbiota and a reversal of the plasma primary/secondary BA ratio, which, in turn, induces weigh-independent metabolic improvements.
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Affiliation(s)
- Eider Talavera-Urquijo
- Department of General & Digestive Surgery, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Marc Beisani
- Department of Surgery, Hospital del Mar, Barcelona, Spain
| | - José M Balibrea
- Department of Gastrointestinal Surgery, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain.
| | - John C Alverdy
- Department of Surgery University of Chicago, Pritzker School of Medicine, Chicago, Illinois
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Singhvi N, Gupta V, Gaur M, Sharma V, Puri A, Singh Y, Dubey GP, Lal R. Interplay of Human Gut Microbiome in Health and Wellness. Indian J Microbiol 2020; 60:26-36. [PMID: 32089571 PMCID: PMC7000599 DOI: 10.1007/s12088-019-00825-x] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 08/30/2019] [Indexed: 12/19/2022] Open
Abstract
The gut microbiome analysis, with specific interest on their direct impact towards the human health, is currently revolutionizing the unexplored frontiers of the pathogenesis and wellness. Although in-depth investigations of gut microbiome, 'the Black Boxes', complexities and functionalities are yet at its infancy, profound evidences are being reported for their concurrent involvement in disease etiology and its treatment. Interestingly, studies from the 'minimal murine' (Oligo-MM12), 'humanized' microbiota gnotobiotic mice models and patient samples, combined with multi-omics and cell biology approaches, have been revealing the implications of these findings in the treatment of gut dysbiosis associated diseases. Nonetheless, due to the inherent heterogeneity of the gut commensals and their unified co-existence with opportunistic pathobionts, it is utmost essential to highlight their functionalities in 'good or bad' gut in human wellness. We have specifically reviewed dietary lifestyle and infectious diseases linked with the gut bacterial consortia to delineate the ecobiotic approaches towards their treatment. This notably includes gut mucosal immunity mediated diseases such as Tuberculosis, IBD, CDI, Type 2 Diabetes, etc. Alongside of each dysbiosis, we have described the current therapeutic advancements of the pre- and probiotics derived from human microbiome studies to restore gut microbial homeostasis. With a continuous running debate on the role of microbiota in above mentioned diseases, we have collected numerous scientific evidences highlighting a previously unanticipated complex involvement of gut microbiome in the potential of human health.
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Affiliation(s)
- Nirjara Singhvi
- Department of Zoology, University of Delhi, Delhi, 110007 India
| | - Vipin Gupta
- Department of Zoology, University of Delhi, Delhi, 110007 India
| | - Mohita Gaur
- Department of Zoology, University of Delhi, Delhi, 110007 India
| | - Vishal Sharma
- Department of Zoology, University of Delhi, Delhi, 110007 India
| | - Akshita Puri
- Department of Zoology, University of Delhi, Delhi, 110007 India
| | - Yogendra Singh
- Department of Zoology, University of Delhi, Delhi, 110007 India
| | - Gyanendra P. Dubey
- Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 75015 Paris, France
| | - Rup Lal
- The Energy and Resources Institute, Darbari Seth Block, IHC Complex, Lodhi Road, New Delhi, 110003 India
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28
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Manipulation of microbiota with probiotics as an alternative for treatment of hepatic encephalopathy. Nutrition 2019; 73:110693. [PMID: 32065881 DOI: 10.1016/j.nut.2019.110693] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 10/21/2019] [Accepted: 11/08/2019] [Indexed: 12/18/2022]
Abstract
Hepatic encephalopathy is a cerebral alteration mainly caused by hepatic insufficiency or portosystemic shunt. It ranges from minimal neurologic manifestations to coma in its overt stage. The multifactorial pathophysiology of hepatic encephalopathy has rendered numerous treatment alternatives, among which the modification of dysbiosis and hyperammonemia are currently considered to be effective, not only clinically, but also regarding cost. Recent work has developed knowledge of probiotics in different clinical settings including the relationship of the gut microenvironment to liver cirrhosis. The aim of this review was to analyze the results of clinical trials on the effect of different probiotics on hepatic encephalopathy.
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Trosko JE. What Can Chemical Carcinogenesis Shed Light on the LNT Hypothesis in Radiation Carcinogenesis? Dose Response 2019; 17:1559325819876799. [PMID: 31565039 PMCID: PMC6755642 DOI: 10.1177/1559325819876799] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 08/27/2019] [Indexed: 12/14/2022] Open
Abstract
To protect the public’s health from exposure to physical, chemical, and microbiological
agents, it is important that any policy be based on rigorous scientifically based
research. The concept of “linear no-threshold” (LNT) has been implemented to provide
guideline exposures to these agents. The practical limitation to testing this hypothesis
is to provide sufficient samples for experimental or epidemiological studies. While there
is no universally accepted understanding of most human diseases, there seems to be better
understanding of cancer that might help resolve the “LNT” model. The public’s concern,
after being exposed to radiation, is the potential of producing cancer. The most rigorous
hypothesis of human carcinogenesis is the “multistage, multimechanism” chemical
carcinogenesis model. The radiation carcinogenesis LNT model, rarely, if ever, built it
into their support. It will be argued that this multistage, multimechanism model of
carcinogenesis, involving the “initiation” of a single cell by a mutagen event, followed
by chronic exposure to threshold levels of epigenetic agents or conditions that stimulate
the clonal expansion of the “initiated” cell, can convert these benign cells to become
invasive and metastatic. This “promotion” process can be interrupted, thereby preventing
these initiated cells from transitioning to the “progression” process of invasion and
metastasis.
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Affiliation(s)
- James E Trosko
- Department Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI, USA
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30
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Bavineni M, Wassenaar TM, Agnihotri K, Ussery DW, Lüscher TF, Mehta JL. Mechanisms linking preterm birth to onset of cardiovascular disease later in adulthood. Eur Heart J 2019; 40:1107-1112. [PMID: 30753448 PMCID: PMC6451766 DOI: 10.1093/eurheartj/ehz025] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Revised: 12/03/2018] [Accepted: 01/18/2019] [Indexed: 12/23/2022] Open
Abstract
Cardiovascular disease (CVD) rates in adulthood are high in premature infants; unfortunately, the underlying mechanisms are not well defined. In this review, we discuss potential pathways that could lead to CVD in premature babies. Studies show intense oxidant stress and inflammation at tissue levels in these neonates. Alterations in lipid profile, foetal epigenomics, and gut microbiota in these infants may also underlie the development of CVD. Recently, probiotic bacteria, such as the mucin-degrading bacterium Akkermansia muciniphila have been shown to reduce inflammation and prevent heart disease in animal models. All this information might enable scientists and clinicians to target pathways to act early to curtail the adverse effects of prematurity on the cardiovascular system. This could lead to primary and secondary prevention of CVD and improve survival among preterm neonates later in adult life.
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Affiliation(s)
- Mahesh Bavineni
- Division of Hospital Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Trudy M Wassenaar
- Molecular Microbiology and Genomics Consultants, Tannenstrasse 7, Zotzenheim D-55576, Germany
- Department of Biomedical Informatics, Arkansas Center for Genomic Epidemiology & Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Kanishk Agnihotri
- Division of Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - David W Ussery
- Department of Biomedical Informatics, Arkansas Center for Genomic Epidemiology & Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Thomas F Lüscher
- Royal Brompton and Harefield Hospitals, London, UK
- Center for Molecular Cardiology, University of Zurich, 4th Floor, Wagistrasse 12, Schlieren, Switzerland
| | - Jawahar L Mehta
- Division of Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
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Zhang S, Shi D, Li M, Li Y, Wang X, Li W. The relationship between gastric microbiota and gastric disease. Scand J Gastroenterol 2019; 54:391-396. [PMID: 30945954 DOI: 10.1080/00365521.2019.1591499] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Traditionally, the stomach was believed to be a sterile organ unsuitable for microbiota growth. However, the discovery of H. pylori subverted this conception. With the development of molecular techniques, an abundance of microbiota of great diversity was found in the stomach. In addition, various lines of evidence suggest that the gastric microbiota plays a critical role in the development and progression of the gastric disease.The gastrointestinal microbiome plays an important role in various physiologic and pathologic processes.
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Affiliation(s)
- Shuyi Zhang
- a Endoscopy Center, Tianjin Union Medical Center , Tianjin , China
| | - Dan Shi
- b Tianjin Medical University Graduate School , Tianjin , China
| | - Muran Li
- c Department of gastroenterology , Tianjin Union Medical Center , Tianjin , China
| | - Yanru Li
- a Endoscopy Center, Tianjin Union Medical Center , Tianjin , China
| | - Ximo Wang
- d Tianjin Clinical Medicine Research Centre for ITCWM Acute abdomen Tianjin Hospital of ITCWM Nankai Hospital , Tianjin , China
| | - Wen Li
- a Endoscopy Center, Tianjin Union Medical Center , Tianjin , China.,b Tianjin Medical University Graduate School , Tianjin , China
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33
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Abulizi N, Quin C, Brown K, Chan YK, Gill SK, Gibson DL. Gut Mucosal Proteins and Bacteriome Are Shaped by the Saturation Index of Dietary Lipids. Nutrients 2019; 11:nu11020418. [PMID: 30781503 PMCID: PMC6412740 DOI: 10.3390/nu11020418] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Revised: 02/01/2019] [Accepted: 02/13/2019] [Indexed: 02/07/2023] Open
Abstract
The dynamics of the tripartite relationship between the host, gut bacteria and diet in the gut is relatively unknown. An imbalance between harmful and protective gut bacteria, termed dysbiosis, has been linked to many diseases and has most often been attributed to high-fat dietary intake. However, we recently clarified that the type of fat, not calories, were important in the development of murine colitis. To further understand the host-microbe dynamic in response to dietary lipids, we fed mice isocaloric high-fat diets containing either milk fat, corn oil or olive oil and performed 16S rRNA gene sequencing of the colon microbiome and mass spectrometry-based relative quantification of the colonic metaproteome. The corn oil diet, rich in omega-6 polyunsaturated fatty acids, increased the potential for pathobiont survival and invasion in an inflamed, oxidized and damaged gut while saturated fatty acids promoted compensatory inflammatory responses involved in tissue healing. We conclude that various lipids uniquely alter the host-microbe interaction in the gut. While high-fat consumption has a distinct impact on the gut microbiota, the type of fatty acids alters the relative microbial abundances and predicted functions. These results support that the type of fat are key to understanding the biological effects of high-fat diets on gut health.
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Affiliation(s)
- Nijiati Abulizi
- Department of Biology, IKBSAS, University of British Columbia, Okanagan campus, Kelowna V1V 1V7, Canada.
| | - Candice Quin
- Department of Biology, IKBSAS, University of British Columbia, Okanagan campus, Kelowna V1V 1V7, Canada.
| | - Kirsty Brown
- Department of Biology, IKBSAS, University of British Columbia, Okanagan campus, Kelowna V1V 1V7, Canada.
| | - Yee Kwan Chan
- Department of Biology, IKBSAS, University of British Columbia, Okanagan campus, Kelowna V1V 1V7, Canada.
| | - Sandeep K Gill
- Department of Biology, IKBSAS, University of British Columbia, Okanagan campus, Kelowna V1V 1V7, Canada.
| | - Deanna L Gibson
- Department of Biology, IKBSAS, University of British Columbia, Okanagan campus, Kelowna V1V 1V7, Canada.
- Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver V6T 1Z3, Canada.
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Cuevas-Sierra A, Ramos-Lopez O, Riezu-Boj JI, Milagro FI, Martinez JA. Diet, Gut Microbiota, and Obesity: Links with Host Genetics and Epigenetics and Potential Applications. Adv Nutr 2019; 10:S17-S30. [PMID: 30721960 PMCID: PMC6363528 DOI: 10.1093/advances/nmy078] [Citation(s) in RCA: 288] [Impact Index Per Article: 48.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Accepted: 09/16/2018] [Indexed: 12/15/2022] Open
Abstract
Diverse evidence suggests that the gut microbiota is involved in the development of obesity and associated comorbidities. It has been reported that the composition of the gut microbiota differs in obese and lean subjects, suggesting that microbiota dysbiosis can contribute to changes in body weight. However, the mechanisms by which the gut microbiota participates in energy homeostasis are unclear. Gut microbiota can be modulated positively or negatively by different lifestyle and dietary factors. Interestingly, complex interactions between genetic background, gut microbiota, and diet have also been reported concerning the risk of developing obesity and metabolic syndrome features. Moreover, microbial metabolites can induce epigenetic modifications (i.e., changes in DNA methylation and micro-RNA expression), with potential implications for health status and susceptibility to obesity. Also, microbial products, such as short-chain fatty acids or membrane proteins, may affect host metabolism by regulating appetite, lipogenesis, gluconeogenesis, inflammation, and other functions. Metabolomic approaches are being used to identify new postbiotics with biological activity in the host, allowing discovery of new targets and tools for incorporation into personalized therapies. This review summarizes the current understanding of the relations between the human gut microbiota and the onset and development of obesity. These scientific insights are paving the way to understanding the complex relation between obesity and microbiota. Among novel approaches, prebiotics, probiotics, postbiotics, and fecal microbiome transplantation could be useful to restore gut dysbiosis.
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Affiliation(s)
- Amanda Cuevas-Sierra
- Department of Nutrition, Food Science, and Physiology and Center for Nutrition Research, University of Navarra, Pamplona, Spain
| | - Omar Ramos-Lopez
- Department of Nutrition, Food Science, and Physiology and Center for Nutrition Research, University of Navarra, Pamplona, Spain
| | - Jose I Riezu-Boj
- Department of Nutrition, Food Science, and Physiology and Center for Nutrition Research, University of Navarra, Pamplona, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
| | - Fermin I Milagro
- Department of Nutrition, Food Science, and Physiology and Center for Nutrition Research, University of Navarra, Pamplona, Spain
- Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
| | - J Alfredo Martinez
- Department of Nutrition, Food Science, and Physiology and Center for Nutrition Research, University of Navarra, Pamplona, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
- Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
- Madrid Institute of Advanced Studies (IMDEA Food), Madrid, Spain
- Address correspondence to JAM (e-mail: )
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Onrust L, Van Driessche K, Ducatelle R, Schwarzer K, Haesebrouck F, Van Immerseel F. Valeric acid glyceride esters in feed promote broiler performance and reduce the incidence of necrotic enteritis. Poult Sci 2018; 97:2303-2311. [PMID: 29562369 DOI: 10.3382/ps/pey085] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Valeric acid is a C5 fatty acid, naturally produced in low concentrations by specific members of the microbiota of the lower intestinal tract. Effects of valeric acid on intestinal health have been poorly investigated. Valeric acid derivatives can be produced as glyceride esters and added to broiler feed. In the current study, experiments were carried out to evaluate the effect of valeric acid glycerides (GVA) on growth performance, on the morphology of the small intestinal mucosa and on protection against necrotic enteritis. In a first feeding trial, Ross-308 chicks were randomly divided into 2 dietary treatment groups and fed either a non-supplemented diet or a diet supplemented with GVA (1.5 g/kg). In the GVA supplemented group, the feed conversion ratio was significantly decreased during the entire trial period (D1-37). In a second trial, gut wall morphology was evaluated. In broilers fed a GVA-containing diet at 5 g/kg, the villus height/crypt depth ratio in the jejunum was significantly increased (P ≤ 0.05), and the crypt depth was significantly decreased at 28 d. In a third trial, immunohistochemistry showed that the density of glucagon-like peptide-2 immunoreactive cells in jejunal and ileal villi from broilers supplemented with GVA (5 g/kg) was significantly increased (P ≤ 0.05) on d 10. In a necrotic enteritis challenge model, a significant reduction of the number of birds with necrotic lesions was found at d 21, using in-feed supplementation of low and high regimen of GVA. These data show that GVA supplementation to broiler feed can decrease the feed conversion, positively affect the morphology of the small intestinal mucosa, increase the density of glucagon-like peptide-2 producing enteroendocrine cells, and reduce the incidence of necrotic enteritis, making GVA a valuable candidate feed additive for broilers.
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Affiliation(s)
- Lonneke Onrust
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820, Merelbeke, Belgium
| | - Karolien Van Driessche
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820, Merelbeke, Belgium
| | - Richard Ducatelle
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820, Merelbeke, Belgium
| | - Koen Schwarzer
- Perstorp BV, Industrieweg 8, NL-5165NH, Waspik, The Netherlands
| | - Freddy Haesebrouck
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820, Merelbeke, Belgium
| | - Filip Van Immerseel
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820, Merelbeke, Belgium
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Flesch AT, Tonial ST, Contu PDEC, Damin DC. Perioperative synbiotics administration decreases postoperative infections in patients with colorectal cancer: a randomized, double-blind clinical trial. ACTA ACUST UNITED AC 2018; 44:567-573. [PMID: 29267553 DOI: 10.1590/0100-69912017006004] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Accepted: 07/20/2017] [Indexed: 02/06/2023]
Abstract
OBJECTIVE to evaluate the effect of perioperative administration of symbiotics on the incidence of surgical wound infection in patients undergoing surgery for colorectal cancer. METHODS We conducted a randomized clinical trial with colorectal cancer patients undergoing elective surgery, randomly assigned to receive symbiotics or placebo for five days prior to the surgical procedure and for 14 days after surgery. We studied 91 patients, 49 in the symbiotics group (Lactobacillus acidophilus 108 to 109 CFU, Lactobacillus rhamnosus 108 to 109 CFU, Lactobacillus casei 108 to 109 CFU, Bifi dobacterium 108 to 109 CFU and fructo-oligosaccharide (FOS) 6g) and 42 in the placebo group. RESULTS surgical site infection occurred in one (2%) patient in the symbiotics group and in nine (21.4%) patients in the control group (p=0.002). There were three cases of intraabdominal abscess and four cases of pneumonia in the control group, whereas we observed no infections in patients receiving symbiotics (p=0.001). CONCLUSION the perioperative administration of symbiotics significantly reduced postoperative infection rates in patients with colorectal cancer. Additional studies are needed to confirm the role of symbiotics in the surgical treatment of colorectal cancer.
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Affiliation(s)
- Aline Taborda Flesch
- - Federal University of Rio Grande do Sul, Post-Graduation Program in Surgical Sciences, Porto Alegre, RS, Brazil
| | - Stael T Tonial
- - Federal University of Rio Grande do Sul, Post-Graduation Program in Surgical Sciences, Porto Alegre, RS, Brazil
| | - Paulo DE Carvalho Contu
- - Federal University of Rio Grande do Sul, Post-Graduation Program in Surgical Sciences, Porto Alegre, RS, Brazil
| | - Daniel C Damin
- - Federal University of Rio Grande do Sul, Post-Graduation Program in Surgical Sciences, Porto Alegre, RS, Brazil
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Spielman LJ, Gibson DL, Klegeris A. Unhealthy gut, unhealthy brain: The role of the intestinal microbiota in neurodegenerative diseases. Neurochem Int 2018; 120:149-163. [PMID: 30114473 DOI: 10.1016/j.neuint.2018.08.005] [Citation(s) in RCA: 186] [Impact Index Per Article: 26.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 08/09/2018] [Accepted: 08/13/2018] [Indexed: 02/08/2023]
Abstract
The number of bacterial cells living within the human body is approximately equal to, or greater than, the total number of human cells. This dynamic population of microorganisms, termed the human microbiota, resides mainly within the gastrointestinal tract. It is widely accepted that highly diverse and stable microbiota promote overall human health. Colonization of the gut with maladaptive and pathogenic microbiota, a state also known as dysbiosis, is associated with a variety of peripheral diseases ranging from type 2 diabetes mellitus to cardiovascular and inflammatory bowel disease. More recently, microbial dysbiosis has been associated with a number of brain pathologies, including autism spectrum disorder, Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), suggesting a direct or indirect communication between intestinal bacteria and the central nervous system (CNS). In this review, we illustrate two pathways implicated in the crosstalk between gut microbiota and CNS involving 1) the vagus nerve and 2) transmission of signaling molecules through the circulatory system and across the blood-brain barrier (BBB). We summarize the available evidence of the specific changes in the intestinal microbiota, as well as microorganism-induced modifications to intestinal and BBB permeability, which have been linked to several neurodegenerative disorders including ALS, AD, and PD. Even though each of these diseases arises from unique pathogenetic mechanisms, all are characterized, at least in part, by chronic neuroinflammation. We provide an interpretation for the substantial evidence that healthy intestinal microbiota have the ability to positively regulate the neuroimmune responses in the CNS. Even though the evidence is mainly associative, it has been suggested that bacterial dysbiosis could contribute to an adverse neuroinflammatory state leading to increased risk of neurodegenerative diseases. Thus, developing strategies for regulating and maintaining healthy intestinal microbiota could be a valid approach for lowering individual risk and prevalence of neurodegenerative diseases.
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Affiliation(s)
| | - Deanna Lynn Gibson
- Department of Biology, University of British Columbia Okanagan Campus, Kelowna, Canada
| | - Andis Klegeris
- Department of Biology, University of British Columbia Okanagan Campus, Kelowna, Canada
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Kim S, Jazwinski SM. The Gut Microbiota and Healthy Aging: A Mini-Review. Gerontology 2018; 64:513-520. [PMID: 30025401 PMCID: PMC6191326 DOI: 10.1159/000490615] [Citation(s) in RCA: 264] [Impact Index Per Article: 37.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Accepted: 06/05/2018] [Indexed: 12/18/2022] Open
Abstract
The gut microbiota shows a wide inter-individual variation, but its within-individual variation is relatively stable over time. A functional core microbiome, provided by abundant bacterial taxa, seems to be common to various human hosts regardless of their gender, geographic location, and age. With advancing chronological age, the gut microbiota becomes more diverse and variable. However, when measures of biological age are used with adjustment for chronological age, overall richness decreases, while a certain group of bacteria associated with frailty increases. This highlights the importance of considering biological or functional measures of aging. Studies using model organisms indicate that age-related gut dysbiosis may contribute to unhealthy aging and reduced longevity. The gut microbiome depends on the host nutrient signaling pathways for its beneficial effects on host health and lifespan, and gut dysbiosis disrupting the interdependence may diminish the beneficial effects or even have reverse effects. Gut dysbiosis can trigger the innate immune response and chronic low-grade inflammation, leading to many age-related degenerative pathologies and unhealthy aging. The gut microbiota communicates with the host through various biomolecules, nutrient signaling-independent pathways, and epigenetic mechanisms. Disturbance of these communications by age-related gut dysbiosis can affect the host health and lifespan. This may explain the impact of the gut microbiome on health and aging.
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Rostami FM, Mousavi H, Mousavi MRN, Shahsafi M. Efficacy of Probiotics in Prevention and Treatment of Infectious Diseases. ACTA ACUST UNITED AC 2018. [DOI: 10.1016/j.clinmicnews.2018.06.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Ghattamaneni NKR, Panchal SK, Brown L. Nutraceuticals in rodent models as potential treatments for human Inflammatory Bowel Disease. Pharmacol Res 2018; 132:99-107. [PMID: 29680446 DOI: 10.1016/j.phrs.2018.04.015] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2017] [Revised: 02/26/2018] [Accepted: 04/16/2018] [Indexed: 12/16/2022]
Abstract
Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation of all or part of the digestive tract. Nutraceuticals include bioactive compounds such as polyphenols with anti-inflammatory activities, thus these products have the potential to treat chronic inflammatory diseases. We have emphasized the role of nutraceuticals in ameliorating the symptoms of IBD in rodent models of human IBD through modulation of key pathogenic mechanisms including dysbiosis, oxidative stress, increased inflammatory cytokines, immune system dysregulation, and inflammatory cell signaling pathways. Nutraceuticals have an important role in IBD patients as a preventive approach to extend remission phases and as a therapeutic intervention to suppress active IBD. Further clinical trials on nutraceuticals with positive results in rodent models are warranted.
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Affiliation(s)
- Naga K R Ghattamaneni
- School of Health and Wellbeing, University of Southern Queensland, Toowoomba, QLD 4350, Australia; Functional Foods Research Group, Institute for Agriculture and the Environment, University of Southern Queensland, Toowoomba, QLD 4350, Australia
| | - Sunil K Panchal
- Functional Foods Research Group, Institute for Agriculture and the Environment, University of Southern Queensland, Toowoomba, QLD 4350, Australia
| | - Lindsay Brown
- School of Health and Wellbeing, University of Southern Queensland, Toowoomba, QLD 4350, Australia; Functional Foods Research Group, Institute for Agriculture and the Environment, University of Southern Queensland, Toowoomba, QLD 4350, Australia.
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Moody KM, Baker RA, Santizo RO, Olmez I, Spies JM, Buthmann A, Granowetter L, Dulman RY, Ayyanar K, Gill JB, Carroll AE. A randomized trial of the effectiveness of the neutropenic diet versus food safety guidelines on infection rate in pediatric oncology patients. Pediatr Blood Cancer 2018; 65. [PMID: 28696047 DOI: 10.1002/pbc.26711] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 05/19/2017] [Accepted: 06/08/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND The neutropenic diet (ND) is prescribed to avoid introduction of bacteria into a host's gastrointestinal tract and reduce infection. Due to a lack of evidence to support the ND, there continues to be debate among pediatric oncologists regarding its usefulness. This prospective randomized controlled trial evaluated the difference in neutropenic infection rates in pediatric oncology patients randomized to Food and Drug Administration approved food safety guidelines (FSGs) versus the ND plus FSGs during one cycle of chemotherapy. PROCEDURE Pediatric patients receiving cancer treatment with myelosuppressive chemotherapy were eligible. Neutropenic infection was the primary outcome and defined as (i) fever with neutropenia or (ii) hospital admission and treatment for clinical infection and neutropenia. The rate of neutropenic infection was compared with Student's t-test for independent samples. Documented infections were identified by comprehensive chart review and compared between groups using a χ2 test. RESULTS One hundred fifty patients were randomly assigned to FSGs (n = 73) or ND + FSGs (n = 77). The most common diagnoses were acute lymphoblastic leukemia (32%) and sarcoma (32%). There was no significant difference between the groups in the percentage of patients who developed neutropenic infection: FSGs 33% versus ND + FSGs 35% (P = 0.78). Patients randomized to ND + FSGs reported that following the diet required more effort than those on FSGs alone. CONCLUSION The ND offers no benefit over FSGs in the prevention of infection in pediatric oncology patients undergoing myelosuppressive chemotherapy and adherence requires more effort for patients and families. Institutions caring for children with cancer should consider replacing ND guidelines with FSGs.
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Affiliation(s)
- Karen M Moody
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana
| | - Rebecca A Baker
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana
| | - Ruth O Santizo
- Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York
| | - Inan Olmez
- Department of Neurology, University of Virginia, Charlottesville, Virginia
| | - Jeanie M Spies
- Rady Children's Hospital, Peckham Center for Cancer and Blood Disorders, San Diego, California
| | - Amanda Buthmann
- The Stephen D. Hassenfeld Children's Center for Cancer and Blood Disorders, New York
| | - Linda Granowetter
- Department of Pediatrics, New York University School of Medicine, New York
| | - Robin Y Dulman
- Pediatric Specialists of Virginia and Inova Fairfax Hospital, Virginia
| | | | - Jonathan B Gill
- Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York
| | - Aaron E Carroll
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana
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Villamil SI, Huerlimann R, Morianos C, Sarnyai Z, Maes GE. Adverse effect of early-life high-fat/high-carbohydrate ("Western") diet on bacterial community in the distal bowel of mice. Nutr Res 2017. [PMID: 29540269 DOI: 10.1016/j.nutres.2017.11.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Obesity and other lifestyle diseases in modern society can be related to historical dietary changes from diets balanced in omega-6 and omega-3 to the unbalanced "Western-type" diet. It is recognized that diet influences the murine and human gut microbiome, and most research indicates that microbial diversity and composition are altered by high-fat diets (HFDs). However, good knowledge about the effects of early exposure to HFD on the maturation and structure of the bacterial community is limited. Using mice as model, we hypothesized that an HFD alters the early dynamic of the gut bacterial community toward an unstable/unhealthy state. By sequencing the V3 and V4 regions of the 16S ribosomal ribonucleic acid gene, we investigated the bacterial community in fecal samples of mice fed a control diet and an HFD at weaning (sampling time 1) and after 8 weeks of dietary intervention (11weeks of age; sampling time 2). Natural temporal microbiome maturation was evidenced by a general increase in microbial diversity and shifts in microbial community between sampling times 1 and 2 toward a mature community. However, the HFD led to significant structural segregation of the microbiome compared with controls; the HFD diet repressed health-enhancing bacteria (eg, Bifidobacterium and Akkermansia) and promoted health-detracting bacteria (ie, those associated with gut disorders, eg, Dorea). We suggest that early-life consumption of HFD negatively impacts the natural gut bacterial community maturation leading toward a potentially persistent unhealthy stage.
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Affiliation(s)
- Sandra Infante Villamil
- College of Sciences and Engineering, Comparative Genomics Centre, James Cook University, Townsville, 4811, Queensland, Australia
| | - Roger Huerlimann
- College of Sciences and Engineering, Comparative Genomics Centre, James Cook University, Townsville, 4811, Queensland, Australia
| | - Christina Morianos
- Laboratory of Psychiatric Neuroscience, and Comparative Genomics Centre, Australian Institute of Tropical Health and Medicine; College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
| | - Zoltan Sarnyai
- Laboratory of Psychiatric Neuroscience, and Comparative Genomics Centre, Australian Institute of Tropical Health and Medicine; College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia.
| | - Gregory E Maes
- College of Sciences and Engineering, Comparative Genomics Centre, James Cook University, Townsville, 4811, Queensland, Australia; Laboratory of Biodiversity and Evolutionary Genomics, University of Leuven (KU Leuven), B-3000 Leuven, Belgium.; Center for Human Genetics, UZ Leuven-Genomics Core, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
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Amitay EL, Werner S, Vital M, Pieper DH, Höfler D, Gierse IJ, Butt J, Balavarca Y, Cuk K, Brenner H. Fusobacterium and colorectal cancer: causal factor or passenger? Results from a large colorectal cancer screening study. Carcinogenesis 2017; 38:781-788. [PMID: 28582482 DOI: 10.1093/carcin/bgx053] [Citation(s) in RCA: 83] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Accepted: 06/01/2017] [Indexed: 12/19/2022] Open
Abstract
Colorectal cancer is a leading cause of morbidity and mortality worldwide in both men and women. The gut microbiome is increasingly recognized as having an important role in human health and disease. Fusobacterium has been identified in former studies as a leading gut bacterium associated with colorectal cancer, but it is still not clear if it plays an oncogenic role. In the current study, fecal samples were collected prior to bowel preparation from participants of screening colonoscopy in the German BliTz study. Using 16S rRNA gene analysis, we examined the presence and relative abundance of Fusobacterium in fecal samples from 500 participants, including 46, 113, 110 and 231 individuals with colorectal cancer, advanced adenomas, non-advanced adenomas and without any neoplasms, respectively. We found that the abundance of Fusobacterium in feces was strongly associated with the presence of colorectal cancer (P-value < 0.0001). This was confirmed by PCR at the species level for Fusobacterium nucleatum. However, no association was seen with the presence of advanced adenomas (P-value = 0.80) or non-advanced adenomas (P-value = 0.80), nor were there any associations observed with dietary or lifestyle habits. Although a causal role cannot be ruled out, our observations, based on fecal microbiome, support the hypothesis that Fusobacterium is a passenger that multiplies in the more favorable conditions caused by the malignant tumor rather than a causal factor in colorectal cancer development.
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Affiliation(s)
- Efrat L Amitay
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), Heidelberg 69120, Germany
| | - Simone Werner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), Heidelberg 69120, Germany
| | - Marius Vital
- Microbial Interactions and Processes Research Group, Helmholtz Centre for Infection Research (HZI), Braunschweig 38124, Germany
| | - Dietmar H Pieper
- Microbial Interactions and Processes Research Group, Helmholtz Centre for Infection Research (HZI), Braunschweig 38124, Germany
| | - Daniela Höfler
- Division of Molecular Diagnostics of Oncogenic Infections, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany
| | - Indra-Jasmin Gierse
- Division of Molecular Diagnostics of Oncogenic Infections, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany
| | - Julia Butt
- Division of Molecular Diagnostics of Oncogenic Infections, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany
| | - Yesilda Balavarca
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg 69120, Germany
| | - Katarina Cuk
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), Heidelberg 69120, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), Heidelberg 69120, Germany.,Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg 69120, Germany.,German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany
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Davis SC, Yadav JS, Barrow SD, Robertson BK. Gut microbiome diversity influenced more by the Westernized dietary regime than the body mass index as assessed using effect size statistic. Microbiologyopen 2017; 6. [PMID: 28677210 PMCID: PMC5552927 DOI: 10.1002/mbo3.476] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Revised: 02/13/2017] [Accepted: 02/22/2017] [Indexed: 12/19/2022] Open
Abstract
Human gut microbiome dysbiosis has been associated with the onset of metabolic diseases and disorders. However, the critical factors leading to dysbiosis are poorly understood. In this study, we provide increasing evidence of the association of diet type and body mass index (BMI) and how they relatively influence the taxonomic structure of the gut microbiota with respect to the causation of gut microbiome dysbiosis. The study included randomly selected Alabama residents (n = 81), including females (n = 45) and males (n = 36). The demographics data included age (33 ± 13.3 years), height (1.7 ± 0.11 meters), and weight (82.3 ± 20.6 kg). The mean BMI was 28.3 ± 7.01, equating to an overweight BMI category. A cross-sectional case-control design encompassing the newly recognized effect size approach to bioinformatics analysis was used to analyze data from donated stool samples and accompanying nutrition surveys. We investigated the microbiome variations in the Bacteroidetes-Firmicutes ratio relative to BMI, food categories, and dietary groups at stratified abundance percentages of <20%, 20%, 30%, 40%, 50%, 60%, and ≥70%. We further investigated variation in the Firmicutes and Bacteroidetes phyla composition (at the genus and species level) in relation to BMI, food categories, and dietary groups (Westernized or healthy). The Pearson Correlation coefficient as an indication of effect size across Alpha diversity indices was used to test the hypothesis (H0 ): increased BMI has greater effect on taxonomic diversity than Westernized diet type, (Ha ): increased BMI does not have a greater effect on taxonomic diversity than Westernized diet type. In conclusion, we rejected the (H0 ) as our results demonstrated that Westernized diet type had an effect size of 0.22 posing a greater impact upon the gut microbiota diversity than an increased BMI with an effect size of 0.16. This implied Westernized diet as a critical factor in causing dysbiosis as compared to an overweight or obese body mass index.
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Affiliation(s)
- Shannon C Davis
- Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL, USA
| | - Jagjit S Yadav
- Microbial Pathogenesis and Immunotoxicology Laboratory, Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, OH, USA
| | - Stephanie D Barrow
- Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL, USA
| | - Boakai K Robertson
- Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL, USA
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Abstract
Microorganisms in humans form complex communities with important functions and differences in each part of the body. The stomach was considered to be a sterile organ until the discovery of Helicobacter pylori, but nowadays, it is possible to demonstrate that other microorganisms beyond H. pylori can colonize the gastric mucosa and that the diverse microbiota ecosystem of the stomach is different from the mouth and the esophagus, and also from the small intestine and large intestine. H. pylori seems to be the most important member of the gastric microbiota with the highest relative abundance when present, but when it is absent, the stomach has a diverse microbiota. Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria are the most abundant phyla in both H. pylori-positive and H. pylori-negative patients. The gastric commensal flora may play some role in the H. pylori-associated carcinogenicity, and differences in the gastric microbiota composition of patients with gastric cancer, intestinal metaplasia, and chronic gastritis are described. The gastric microbiota changed gradually from non-atrophic gastritis to intestinal metaplasia, and to gastric cancer (type intestinal).
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Doctor A, Zimmerman J, Agus M, Rajasekaran S, Wardenburg JB, Fortenberry J, Zajicek A, Typpo K. Pediatric Multiple Organ Dysfunction Syndrome: Promising Therapies. Pediatr Crit Care Med 2017; 18:S67-S82. [PMID: 28248836 PMCID: PMC5333132 DOI: 10.1097/pcc.0000000000001053] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVE To describe the state of the science, identify knowledge gaps, and offer potential future research questions regarding promising therapies for children with multiple organ dysfunction syndrome presented during the Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop on Pediatric Multiple Organ Dysfunction Syndrome (March 26-27, 2015). DATA SOURCES Literature review, research data, and expert opinion. STUDY SELECTION Not applicable. DATA EXTRACTION Moderated by an expert from the field, issues relevant to the association of multiple organ dysfunction syndrome with a variety of conditions were presented, discussed, and debated with a focus on identifying knowledge gaps and research priorities. DATA SYNTHESIS Summary of presentations and discussion supported and supplemented by relevant literature. CONCLUSIONS Among critically ill children, multiple organ dysfunction syndrome is relatively common and associated with significant morbidity and mortality. For outcomes to improve, effective therapies aimed at preventing and treating this condition must be discovered and rigorously evaluated. In this article, a number of potential opportunities to enhance current care are highlighted including the need for a better understanding of the pharmacokinetics and pharmacodynamics of medications, the effect of early and optimized nutrition, and the impact of effective glucose control in the setting of multiple organ dysfunction syndrome. Additionally, a handful of the promising therapies either currently being implemented or developed are described. These include extracorporeal therapies, anticytokine therapies, antitoxin treatments, antioxidant approaches, and multiple forms of exogenous steroids. For the field to advance, promising therapies and other therapies must be assessed in rigorous manner and implemented accordingly.
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Affiliation(s)
- Allan Doctor
- Departments of Pediatrics (Critical Care Medicine) and Biochemistry, Washington University in Saint Louis
| | - Jerry Zimmerman
- Department of Pediatrics (Critical Care Medicine), University of Washington, Seattle, WA
| | - Michael Agus
- Department of Pediatrics (Critical Care Medicine), Harvard University, Boston, MA
| | - Surender Rajasekaran
- Department of Pediatrics (Critical Care Medicine), Michigan State University, Grand Rapids, MI
| | | | - James Fortenberry
- Department of Pediatrics (Critical Care Medicine), Emory University, Atlanta, GA
| | - Anne Zajicek
- Obstetric and Pediatric Pharmacology and Therapeutics Branch, NICHD
| | - Katri Typpo
- Department of Pediatrics (Critical Care Medicine), University of Arizona, Phoenix, AZ
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Belik J, Shifrin Y, Arning E, Bottiglieri T, Pan J, Daigneault MC, Allen-Vercoe E. Intestinal microbiota as a tetrahydrobiopterin exogenous source in hph-1 mice. Sci Rep 2017; 7:39854. [PMID: 28079055 PMCID: PMC5227711 DOI: 10.1038/srep39854] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Accepted: 11/29/2016] [Indexed: 01/07/2023] Open
Abstract
Tetrahydrobiopterin (BH4) is a cofactor of a number of regulatory enzymes. Although there are no known BH4 exogenous sources, the tissue content of this biopterin increases with age in GTP cyclohydrolase 1-deficient hyperphenylalaninemia-1 (hph-1) mice. Since certain bacteria are known to generate BH4, we hypothesize that generation of this biopterin by the intestinal microbiota contributes to its tissue increase in hph-1 adult mice. The goal of this study was to comparatively evaluate hph-1 mice and wild-type C57Bl/6 controls for the presence of intestinal BH4-producing bacteria. Newborn and adult mice fecal material was screened for 6-pyruvoyltetrahydropterin synthase (PTPS-2) an enzyme only present in BH4-generating bacteria. Adult, but not newborn, wild-type control and hph-1 mouse fecal material contained PTPS-2 mRNA indicative of the presence of BH4-generating bacteria. Utilizing chemostat-cultured human fecal bacteria, we identified the PTPS-2-producing bacteria as belonging to the Actinobacteria phylum. We further confirmed that at least two PTPS-2-producing species, Aldercreutzia equolifaciens and Microbacterium schleiferi, generate BH4 and are present in hph-1 fecal material. In conclusion, intestinal Actinobacteria generate BH4. This finding has important translational significance, since manipulation of the intestinal flora in individuals with congenital biopterin deficiency may allow for an increase in total body BH4 content.
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Affiliation(s)
- Jaques Belik
- Physiology & Experimental Medicine Program, The Hospital for Sick Children Research Institute, Toronto, Ontario M5G 1X8, Canada
- Department of Paediatrics and Physiology, University of Toronto, Toronto, Ontario, M5G 1X8 Canada
| | - Yulia Shifrin
- Physiology & Experimental Medicine Program, The Hospital for Sick Children Research Institute, Toronto, Ontario M5G 1X8, Canada
| | - Erland Arning
- Baylor Research Institute, Institute of Metabolic Disease, Dallas, TX, 75226, USA
| | - Teodoro Bottiglieri
- Baylor Research Institute, Institute of Metabolic Disease, Dallas, TX, 75226, USA
| | - Jingyi Pan
- Physiology & Experimental Medicine Program, The Hospital for Sick Children Research Institute, Toronto, Ontario M5G 1X8, Canada
| | | | - Emma Allen-Vercoe
- Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, N1G 2W1 Canada
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Antimicrobial growth promoter use in livestock: a requirement to understand their modes of action to develop effective alternatives. Int J Antimicrob Agents 2017; 49:12-24. [PMID: 27717740 DOI: 10.1016/j.ijantimicag.2016.08.006] [Citation(s) in RCA: 106] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Revised: 07/25/2016] [Accepted: 08/08/2016] [Indexed: 02/06/2023]
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Abstract
PURPOSE OF REVIEW We explore how a global shift in the food system caused by global economic growth, increase in available food per capita and in food processing is a driver of the obesity epidemic. RECENT FINDINGS Economic development in most areas of the world has resulted in increased purchasing power and available per capita food. Supermarkets and a growing fast-food industry have transformed our dietary pattern. Ultra-processed food rich on sugars and saturated fat is now the major source of energy in most countries. The shift in food supply is considered a major driver of the obesity epidemic and the increasing prevalence of accompanying complications, such as type 2 diabetes, cardiovascular disease and cancer. However, the global shift might also have direct effects on the increase in type 2 diabetes, cardiovascular disease and cancer, independently of overweight and obesity. The shift in the food supply is a major driver of the obesity epidemic.
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Affiliation(s)
| | | | - Peter Rossing
- Steno Diabetes Center, Gentofte, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Health, Aarhus University, Aarhus, Denmark
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50
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Chan YK, Brar MS, Kirjavainen PV, Chen Y, Peng J, Li D, Leung FCC, El-Nezami H. High fat diet induced atherosclerosis is accompanied with low colonic bacterial diversity and altered abundances that correlates with plaque size, plasma A-FABP and cholesterol: a pilot study of high fat diet and its intervention with Lactobacillus rhamnosus GG (LGG) or telmisartan in ApoE -/- mice. BMC Microbiol 2016; 16:264. [PMID: 27821063 PMCID: PMC5100306 DOI: 10.1186/s12866-016-0883-4] [Citation(s) in RCA: 93] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2015] [Accepted: 10/29/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Atherosclerosis appears to have multifactorial causes - microbial component like lipopolysaccharides (LPS) and other pathogen associated molecular patterns may be plausible factors. The gut microbiota is an ample source of such stimulants, and its dependent metabolites and altered gut metagenome has been an established link to atherosclerosis. In this exploratory pilot study, we aimed to elucidate whether microbial intervention with probiotics L. rhamnosus GG (LGG) or pharmaceuticals telmisartan (TLM) could improve atherosclerosis in a gut microbiota associated manner. METHODS Atherosclerotic phenotype was established by 12 weeks feeding of high fat (HF) diet as opposed to normal chow diet (ND) in apolipoprotein E knockout (ApoE-/-) mice. LGG or TLM supplementation to HF diet was studied. RESULTS Both LGG and TLM significantly reduced atherosclerotic plaque size and improved various biomarkers including endotoxin to different extents. Colonial microbiota analysis revealed that TLM restored HF diet induced increase in Firmicutes/Bacteroidetes ratio and decrease in alpha diversity; and led to a more distinct microbial clustering closer to ND in PCoA plot. Eubacteria, Anaeroplasma, Roseburia, Oscillospira and Dehalobacteria appeared to be protective against atherosclerosis and showed significant negative correlation with atherosclerotic plaque size and plasma adipocyte - fatty acid binding protein (A-FABP) and cholesterol. CONCLUSION LGG and TLM improved atherosclerosis with TLM having a more distinct alteration in the colonic gut microbiota. Altered bacteria genera and reduced alpha diversity had significant correlations to atherosclerotic plaque size, plasma A-FABP and cholesterol. Future studies on such bacterial functional influence in lipid metabolism will be warranted.
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Affiliation(s)
- Yee Kwan Chan
- 5S12, Kadoorie Biological Sciences Building, School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
| | - Manreetpal Singh Brar
- 5N01, Kadoorie Biological Sciences Building, School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
| | - Pirkka V Kirjavainen
- Food and Research Health Centre, University of Eastern Finland, Joensuu, Finland
| | - Yan Chen
- L943, Laboratory Block, Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong
| | - Jiao Peng
- L943, Laboratory Block, Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong
| | - Daxu Li
- L943, Laboratory Block, Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong
| | - Frederick Chi-Ching Leung
- 5N01, Kadoorie Biological Sciences Building, School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong.,Bioinformatics Center, Nanjing Agricultural University, Nanjing, China
| | - Hani El-Nezami
- 5S12, Kadoorie Biological Sciences Building, School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong. .,Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. .,5S13, Kadoorie Biological Sciences Building, The University of Hong Kong, Pokfulam, Hong Kong.
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