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Álvarez-Herms J, González-Benito A, Corbi F, Odriozola A. What if gastrointestinal complications in endurance athletes were gut injuries in response to a high consumption of ultra-processed foods? Please take care of your bugs if you want to improve endurance performance: a narrative review. Eur J Appl Physiol 2024; 124:383-402. [PMID: 37839038 DOI: 10.1007/s00421-023-05331-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 09/20/2023] [Indexed: 10/17/2023]
Abstract
To improve performance and recovery faster, athletes are advised to eat more often than usual and consume higher doses of simple carbohydrates, during and after exercise. Sports energetic supplements contain food additives, such as artificial sweeteners, emulsifiers, acidity regulators, preservatives, and salts, which could be harmful to the gut microbiota and impair the intestinal barrier function. The intestinal barrier plays a critical function in bidirectionally regulation of the selective transfer of nutrients, water, and electrolytes, while preventing at the same time, the entrance of harmful substances (selective permeability). The gut microbiota helps to the host to regulate intestinal homeostasis through metabolic, protective, and immune functions. Globally, the gut health is essential to maintain systemic homeostasis in athletes, and to ensure proper digestion, metabolization, and substrate absorption. Gastrointestinal complaints are an important cause of underperformance and dropout during endurance events. These complications are directly related to the loss of gut equilibrium, mainly linked to microbiota dysbiosis and leaky gut. In summary, athletes must be cautious with the elevated intake of ultra-processed foods and specifically those contained on sports nutrition supplements. This review points out the specific nutritional interventions that should be implemented and/or discontinued depending on individual gut functionality.
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Affiliation(s)
- Jesús Álvarez-Herms
- Phymolab (Physiology and Molecular Laboratory), Collado Hermoso, Segovia, Spain.
- Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Bilbao, Spain.
| | - A González-Benito
- Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Bilbao, Spain
| | - F Corbi
- Institut Nacional d'Educació Física de Catalunya (INEFC), University of Lleida (UdL), Lleida, Spain
| | - A Odriozola
- Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Bilbao, Spain
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Effect of a Proton Pump Inhibitor on the Duodenum Microbiome of Gastric Ulcer Patients. Life (Basel) 2022; 12:life12101505. [PMID: 36294939 PMCID: PMC9605190 DOI: 10.3390/life12101505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 09/21/2022] [Accepted: 09/21/2022] [Indexed: 11/19/2022] Open
Abstract
The gut microbiota are regarded as a functional organ that plays a substantial role in human health and disease. Proton pump inhibitors (PPIs) are widely used in medicine but can induce changes in the overall gut microbiome and cause disease-associated dysbiosis. The microbiome of the duodenum has not been sufficiently studied, and the effects of PPIs on the duodenal microbiome are poorly understood. In this study, we investigated the effect of PPI administration on duodenum microbiota in patients with a gastric ulcer. A total of 12 gastric ulcer patients were included, and PPI (Ilaprazole, Noltec®, 10 mg) was prescribed in all patients for 4 weeks. A total of 17 samples from the second portion of the duodenum were analyzed. Microbiome compositions were assessed by sequencing the V3–V4 region of the 16s rRNA gene (Miseq). Changes in microbiota compositions after 4 weeks of PPI treatment were analyzed. a-Diversity was higher after PPI treatment (p = 0.02, at Chao1 index), and β-diversity was significantly different after treatment (p = 0.007). Welch’s t-test was used to investigate changes in phyla, genus, and species level, and the abundance of Akkermansia muciniphila, belonging to the phylum Verrucomicrobia, and Porphyromonas endodontalis, belonging to the phylum Bacteroidetes, was significantly increased after treatment (p = 0.044 and 0.05). PPI administration appears to induce duodenal microbiome dysbiosis while healing gastric ulcers. Further large-scale studies on the effects of PPIs on the duodenal microbiome are required.
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Abstract
AbstractDescriptions of the small intestinal microbiota are deficient and conflicting. We aimed to get a reliable description of the jejunal bacterial microbiota by investigating samples from two separate jejunal segments collected from the luminal mucosa during surgery. Sixty patients with morbid obesity selected for elective gastric bypass surgery were included in this survey. Samples collected by rubbing a swab against the mucosa of proximal and mid jejunal segments were characterized both quantitatively and qualitatively using a combination of microbial culture, a universal quantitative PCR and 16S deep sequencing. Within the inherent limitations of partial 16S sequencing, bacteria were assigned to the species level. By microbial culture, 53 patients (88.3%) had an estimated bacterial density of < 1600 cfu/ml in both segments whereof 31 (51.7%) were culture negative in both segments corresponding to a bacterial density below 160 cfu/ml. By quantitative PCR, 46 patients (76.7%) had less than 104 bacterial genomes/ml in both segments. The most abundant and frequently identified species by 16S deep sequencing were associated with the oral cavity, most often from the Streptococcus mitis group, the Streptococcus sanguinis group, Granulicatella adiacens/para-adiacens, the Schaalia odontolytica complex and Gemella haemolysans/taiwanensis. In general, few bacterial species were identified per sample and there was a low consistency both between the two investigated segments in each patient and between patients. The jejunal mucosa of fasting obese patients contains relatively few microorganisms and a core microbiota could not be established. The identified microbes are likely representatives of a transient microbiota and there is a high degree of overlap between the most frequently identified species in the jejunum and the recently described ileum core microbiota.
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Chemically Protected Sodium Butyrate Improves Growth Performance and Early Development and Function of Small Intestine in Broilers as One Effective Substitute for Antibiotics. Antibiotics (Basel) 2022; 11:antibiotics11020132. [PMID: 35203735 PMCID: PMC8868412 DOI: 10.3390/antibiotics11020132] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 01/07/2022] [Accepted: 01/12/2022] [Indexed: 01/14/2023] Open
Abstract
The purpose of this study was to investigate the effects of chemically protected sodium butyrate (CSB) on growth performance and the early development and function of small intestine in broilers as one potential substitute for antibiotics. A total of 192 one-day-old Arbor Acres male broilers were randomly assigned into three dietary treatment groups (eight replicates per treatment): the control (CON) diet; ANT diet, CON diet supplemented with the antibiotics (enramycin, 8 mg/kg and aureomycin, 100 mg/kg); CSB diet, CON diet supplemented with 1000 mg/kg CSB, respectively. The results showed that dietary CSB and antibiotics addition significantly improved the growth performance of broilers by increasing the body weight gain (BWG) and feed conversion ratio (FCR) during different stages (p < 0.05). On day 21, the supplement of CSB in diet improved the structure of small intestine (duodenum, jejunum, and ileum) in broilers by increasing the ratio of villus height to crypt depth (VH/CD) (p < 0.05) and enhanced the butyric acid (BA) (p < 0.05) and total short chain fatty acids (SCFA) concentrations of small intestine (jejunum and ileum) compared with the CON and ANT diets. Besides that, the superoxide dismutase (SOD), total antioxidant capacity (TAC) and TAC to malondialdehyde (TAC/MDA) ratio of the ileal and jejunal mucosa were significantly higher (p < 0.05) in the CSB and ANT than in the CON. In addition, the supplement of CSB in diet markedly significantly enhanced α-amylase, lipase, and trypsin activities of the ileum (p < 0.05) as compared to the ANT diet. 16S rRNA gene sequencing indicated that CSB markedly increased the microbiota diversity of ileum in broilers at 21 days of age as compared to CON and ANT (p < 0.05). Furthermore, we found that Firmicutes was the predominant phyla and Lactobacillus was the major genus in the ileum of broilers. Compared with the ANT diet, the supplement of CSB in diet increased the relative abundance of some genera microbiota (e.g., Candidatus_Arthromitus, Romboutsia) by decreasing the relative abundance of Lactobacillus. Moreover, Akkermansia in the CSB was the highest in comparison to that in the CON and ANT. In addition, Kitasatospora that belongs to the phylum Actinobacteriota was only found in ileum of broilers fed the ANT diet. In summary, the supplement of 1000 mg/kg CSB in the diet improved the growth performance by promoting early development and function of the small intestine, which is associated with the regulation of intestinal flora and reestablishment of micro-ecological balance in broilers. Thus, CSB has great potential value as one of effective substitutes for in-feed antibiotics in the broiler industry.
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Zhang J, Hoedt EC, Liu Q, Berendsen E, Teh JJ, Hamilton A, O' Brien AW, Ching JYL, Wei H, Yang K, Xu Z, Wong SH, Mak JWY, Sung JJY, Morrison M, Yu J, Kamm MA, Ng SC. Elucidation of Proteus mirabilis as a Key Bacterium in Crohn's Disease Inflammation. Gastroenterology 2021; 160:317-330.e11. [PMID: 33011176 DOI: 10.1053/j.gastro.2020.09.036] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 08/20/2020] [Accepted: 09/23/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS Proteus spp, Gram-negative facultative anaerobic bacilli, have recently been associated with Crohn's disease (CD) recurrence after intestinal resection. We investigated the genomic and functional role of Proteus as a gut pathogen in CD. METHODS Proteus spp abundance was assessed by ure gene-specific polymerase chain in 54 pairs of fecal samples and 101 intestinal biopsies from patients with CD and healthy controls. The adherence, invasion, and intracellular presence of 2 distinct isolates of Proteus mirabilis in epithelial cells were evaluated using immunofluorescence and electron microscopy. Intracellular gene expression profiles and regulated pathways were analyzed by RNA sequencing and KEGG pathway analysis. Biologic functions of 2 isolates of P mirabilis were determined by in vitro cell culture, and in vivo using conventional mice and germ-free mice. RESULTS Proteus spp were significantly more prevalent and abundant in fecal samples and colonic tissue of patients with CD than controls. A greater abundance of the genus Fusobacterium and a lesser abundance of the genus Faecalibacterium were seen in patients with CD with a high Proteus spp abundance. All 24 Proteus monoclones isolated from patients with CD belonged to members of P mirabilis lineages and 2 isolates, recovered from stool or mucosa, were used in further studies. Mice gavaged with either P mirabilis strain had more severe colonic inflammation. Co-culture of the isolates with epithelial cell lines showed bacterial adherence, invasion, increased production of pro-inflammatory cytokines IL-18 and IL-1α, and cell necrosis. Both isolates induced key pro-inflammatory pathways, including NOD-like receptor signaling, Jak-STAT signaling, and MAPK signaling, and induced pro-inflammatory genes and activated inflammation-related pathways in gnotobiotic mice. CONCLUSIONS P mirabilis in the gut is associated with CD and can induce inflammation in cells and animal models of colitis. P mirabilis can act as a pathobiont and play a crucial role in the pathogenesis of CD.
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Affiliation(s)
- Jingwan Zhang
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
| | - Emily C Hoedt
- The University of Queensland Diamantina Institute, Faculty of Medicine, Brisbane, Australia; APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Qin Liu
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
| | - Erwin Berendsen
- The University of Queensland Diamantina Institute, Faculty of Medicine, Brisbane, Australia
| | - Jing Jie Teh
- The University of Queensland Diamantina Institute, Faculty of Medicine, Brisbane, Australia
| | - Amy Hamilton
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; Department of Medicine, The University of Melbourne, Melbourne, Australia
| | - Amy Wilson O' Brien
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; Department of Medicine, The University of Melbourne, Melbourne, Australia
| | - Jessica Y L Ching
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
| | - Hong Wei
- Department of Laboratory Animal Science at the Third Military Medical University in Chongqing, China
| | - Keli Yang
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
| | - Zhilu Xu
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
| | - Sunny H Wong
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China; Center for Gut Microbiota Research, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Joyce W Y Mak
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
| | - Joseph J Y Sung
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
| | - Mark Morrison
- The University of Queensland Diamantina Institute, Faculty of Medicine, Brisbane, Australia.
| | - Jun Yu
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China; Center for Gut Microbiota Research, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
| | - Michael A Kamm
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; Department of Medicine, The University of Melbourne, Melbourne, Australia.
| | - Siew C Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China; Center for Gut Microbiota Research, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
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Mucosal microbiome dysbiosis associated with duodenum bulb inflammation. Microb Pathog 2020; 150:104711. [PMID: 33385493 DOI: 10.1016/j.micpath.2020.104711] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 12/15/2020] [Accepted: 12/17/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND There is high morbidity in clinical patients with duodenum bulb inflammation. Mucosa-associated microbiota, which are closely related to inflammatory processes, may have a pathogenic role, but the duodenum bulb microbial signature is poorly studied. OBJECTIVE This study aimed to characterize microbial changes associated with duodenum bulb inflammation. METHODS Mucosal biopsy is commonly used to assess microbial communities associated with the intestinal mucosa. Sixteen patients (8 with duodenum bulb inflammation and 8 controls) underwent gastroscopy, and duodenal bulb biopsies were obtained. Diagnoses were based on both endoscopic and histological findings. To determine microbiota composition and diversity, 454 pyrosequencing of bacterial 16S rRNA and multiple bioinformatics analyses were performed. OTU-level alpha diversity indices, such as the Chao1 richness estimator, abundance-based coverage estimator (ACE) metric, Shannon diversity index, and Simpson index, were calculated using the OTU table in QIIME. RESULTS More OTUs were identified in the normal samples (781) than in the inflammatory samples (553). Metastats analysis identified 19 phyla and 97 genera that were significantly different between the two groups, and the beta diversity was significantly different between the two groups (unweighted UniFrac: P = 0.001; weighted UniFrac: P = 0.001). For all individuals, composition analyses showed that the most abundant phyla in the duodenal bulb samples were Fusobacteria, Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria. The phylogenetic diversity of the microbiota in the duodenal bulbs of healthy volunteers was higher than that in volunteers with inflammation. Dominant microbes differed between the DN samples and DI samples. The most frequently represented genera in the DN samples were Cetobacterium, Aeromonadaceae, and Clostridium (accounting for 58.4%, 8.5%, and 4.8% of the total, respectively), and the dominant genera in the DI samples were Cetobacterium, Cupriavidus, and Helicobacter (accounting for 43.6%, 13.1%, 4.5% of the total, respectively). Significant differences in the microbiota were observed between those exhibiting an inflammatory state and the controls. CONCLUSIONS These results confirm that the dominant species in duodenum bulbs differ between healthy subjects and patients with inflammation and that mucosal microbiome dysbiosis is involved in the development of duodenum bulb inflammation.
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The cultivable microbiota of the human distal ileum. Clin Microbiol Infect 2020; 27:912.e7-912.e13. [PMID: 32835795 DOI: 10.1016/j.cmi.2020.08.021] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 08/14/2020] [Accepted: 08/15/2020] [Indexed: 12/17/2022]
Abstract
OBJECTIVES The existing literature on the microbiota of the ileum is inconsistent. To further characterize the microbiota, we analysed samples obtained directly from resected ileums used for urinary diversion after radical cystectomy. METHODS We included 150 patients with bladder cancer operated on from March 2016 to March 2019. Samples obtained by rubbing a swab against the ileal mucosa 25 cm from the ileocecal valve were cultivated at the local laboratory. Microbial colonies were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF). RESULTS The microbial density of the distal ileum was low. Among our samples, 79% (95% confidence interval (CI) 71%, 84%) harboured less than 1.6 × 104 cfu/mL, whereas 36% (95% CI 28%, 44%) harboured less than 1.6 × 103 cfu/mL. The flora was dominated by viridans streptococci, Candida, Actinomyces, Rothia and Lactobacillus species. Colon-related bacteria i.e. strict anaerobic bacteria, Enterobacteriales and enterococci, were recovered from 14% of the samples. Constipation was associated with increased recovery of colon-related bacteria. Antibiotic treatment prior to surgical procedures did not affect culture results. Increased age was significantly associated with more substantial fungal growth and use of proton pump inhibitors seemed to increase both bacterial and fungal growth. CONCLUSIONS The microbiota of the human distal ileum is sparse and differs significantly from the colonic microbiota both quantitatively and by composition. These findings contradict recent metagenomics studies based on samples collected by retrograde colonoscopy and emphasize the crucial importance of adequate sampling techniques.
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Fan HN, Zhu P, Lu YM, Guo JH, Zhang J, Qu GQ, Zhu JS. Mild changes in the mucosal microbiome during terminal ileum inflammation. Microb Pathog 2020; 142:104104. [PMID: 32120004 DOI: 10.1016/j.micpath.2020.104104] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Revised: 02/22/2020] [Accepted: 02/24/2020] [Indexed: 12/30/2022]
Abstract
Patients with inflammation in the terminal ileum have high morbidity. In genetically susceptible hosts, chronic intestinal inflammation targeting the resident intestinal microbiota develops, but the microbial signature of the terminal ileum is poorly studied. To improve understanding of the mechanisms underlying the high prevalence of terminal ileum inflammation, we used 16S rRNA sequencing to analyse the mucosa-associated microbiota of the terminal ileum under intestinal homeostasis and inflammation conditions. Mucosal biopsy is the most commonly used sampling technique for assessing microbial communities associated with the intestinal mucosa. Thirty patients (15 with terminal ileum inflammation and 15 controls) underwent colonoscopy and biopsies were taken from the terminal ileum. Diagnosis depended on a combination of endoscopic and histological factors. To determine the composition and diversity of the microbiota, the 16S rRNA was analysed, and a variety of bioinformatics analyses were performed. Among the patients, composition analysis showed that the most abundant phyla identified in the terminal ileum samples were Fusobacteria, Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria. At the phylum level, the relative proportion of Bacteroidetes was lower in patients with inflammation than in control patients. In addition, there was an increase in the abundance of the phyla Proteobacteria and Lentisphaerae in patients with inflammation. The abundances of the dominant microbes in the terminal ileum were not significantly different between patients in an inflammatory state and controls. These results confirm that partial dysbiosis of the intestinal mucosa-associated microbiota composition is associated with terminal ileum inflammation.
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Affiliation(s)
- Hui-Ning Fan
- Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
| | - Pei Zhu
- Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
| | - Yun-Min Lu
- Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
| | - Jing-Hui Guo
- Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
| | - Jing Zhang
- Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
| | - Guo-Qiang Qu
- Department of Gastroenterology, Shanghai University of Medicine and Health Sciences Affiliated Sixth People's Hospital East Campus, Shanghai, 201306, China
| | - Jin-Shui Zhu
- Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
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Wei L, Li Y, Tang W, Sun Q, Chen L, Wang X, Liu Q, Yu S, Yu S, Liu C, Ma X. Chronic Unpredictable Mild Stress in Rats Induces Colonic Inflammation. Front Physiol 2019; 10:1228. [PMID: 31616319 PMCID: PMC6764080 DOI: 10.3389/fphys.2019.01228] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 09/09/2019] [Indexed: 01/01/2023] Open
Abstract
Chronic psychological stress is associated with an increased risk for relapse of inflammatory bowel diseases (IBD) and impedes the treatment of this condition. However, the impact of stress on the risk of IBD onset remains unclear. The goal of the present study was to examine whether chronic unpredictable mild stress (CUMS) could initiate or aggravate the onset of colon inflammation in rats which, in turn, would be capable of triggering bowel disease. We found that CUMS exposure increased infiltration of CD-45 positive cells and MPO activity, as well as augmented the expression of the inflammatory cytokines, IFN-γ and IL-6 within the colon of these rats. In addition, CUMS treatment changed the composition and diversity of gut microbiota and enhanced intestinal epithelial permeability, indicating the presence of a defect in the intestinal barrier. This CUMS-induced disruption of mucosal barrier integrity was associated with a reduction in expression of the tight junction protein, occludin 1, and an inhibition in mucosal layer functioning via reductions in goblet cells. Results from bacterial cultures revealed an increased presence of bacterial invasion after CUMS treatment as compared with that observed in controls. Thus, our data indicate that CUMS treatment induces alterations of the fecal microbiome and intestinal barrier defects, which facilitates bacterial invasion into colonic mucosa and further exacerbates inflammatory reactions within the colon. Accordingly, chronic stress may predispose patients to gastrointestinal infection and increase the risk of inflammation-related gut diseases.
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Affiliation(s)
- Lina Wei
- Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Ye Li
- Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Wenjun Tang
- Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Qian Sun
- Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Lixin Chen
- Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Xia Wang
- Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Qingyi Liu
- Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Siqi Yu
- Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Shuyan Yu
- Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Chuanyong Liu
- Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Xuelian Ma
- Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, China
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Kastl AJ, Terry NA, Wu GD, Albenberg LG. The Structure and Function of the Human Small Intestinal Microbiota: Current Understanding and Future Directions. Cell Mol Gastroenterol Hepatol 2019; 9:33-45. [PMID: 31344510 PMCID: PMC6881639 DOI: 10.1016/j.jcmgh.2019.07.006] [Citation(s) in RCA: 208] [Impact Index Per Article: 34.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Revised: 07/17/2019] [Accepted: 07/17/2019] [Indexed: 02/07/2023]
Abstract
Despite growing literature characterizing the fecal microbiome and its association with health and disease, few studies have analyzed the microbiome of the small intestine. Here, we examine what is known about the human small intestinal microbiota in terms of community structure and functional properties. We examine temporal dynamics of select bacterial populations in the small intestine, and the effects of dietary carbohydrates and fats on shaping these populations. We then evaluate dysbiosis in the small intestine in several human disease models, including small intestinal bacterial overgrowth, short-bowel syndrome, pouchitis, environmental enteric dysfunction, and irritable bowel syndrome. What is clear is that the bacterial biology, and mechanisms of bacteria-induced pathophysiology, are enormously broad and elegant in the small intestine. Studying the small intestinal microbiota is challenged by rapidly fluctuating environmental conditions in these intestinal segments, as well as the complexity of sample collection and bioinformatic analysis. Because the functionality of the digestive tract is determined primarily by the small intestine, efforts must be made to better characterize this unique and important microbial ecosystem.
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Affiliation(s)
- Arthur J. Kastl
- Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania,Correspondence Address correspondence to: Arthur J. Kastl Jr, MD, Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, 3401 Civic Center Boulevard, 7NW, Philadelphia, Pennsylvania 19104. fax: (215) 590-3606.
| | - Natalie A. Terry
- Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Gary D Wu
- Division of Gastroenterology, Hepatology, and Nutrition, The University of Pennsylvania, Philadelphia, Pennsylvania
| | - Lindsey G. Albenberg
- Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
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Abstract
The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabolism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBTand the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allograft rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host-microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.
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Marlicz W, Yung DE, Skonieczna-Żydecka K, Loniewski I, van Hemert S, Loniewska B, Koulaouzidis A. From clinical uncertainties to precision medicine: the emerging role of the gut barrier and microbiome in small bowel functional diseases. Expert Rev Gastroenterol Hepatol 2017; 11:961-978. [PMID: 28618973 DOI: 10.1080/17474124.2017.1343664] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Over the last decade, remarkable progress has been made in the understanding of disease pathophysiology. Many new theories expound on the importance of emerging factors such as microbiome influences, genomics/omics, stem cells, innate intestinal immunity or mucosal barrier complexities. This has introduced a further dimension of uncertainty into clinical decision-making, but equally, may shed some light on less well-understood and difficult to manage conditions. Areas covered: Comprehensive review of the literature on gut barrier and microbiome relevant to small bowel pathology. A PubMed/Medline search from 1990 to April 2017 was undertaken and papers from this range were included. Expert commentary: The scenario of clinical uncertainty is well-illustrated by functional gastrointestinal disorders (FGIDs). The movement towards achieving a better understanding of FGIDs is expressed in the Rome IV guidelines. Novel diagnostic and therapeutic protocols focused on the GB and SB microbiome can facilitate diagnosis, management and improve our understanding of the underlying pathological mechanisms in FGIDs.
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Affiliation(s)
- Wojciech Marlicz
- a Department of Gastroenterology , Pomeranian Medical University , Szczecin , Poland
| | - Diana E Yung
- b Centre for Liver and Digestive Disorders , Royal Infirmary of Edinburgh , Edinburgh , United Kingdom
| | | | - Igor Loniewski
- c Department of Biochemistry and Human Nutrition , Pomeranian Medical University , Szczecin , Poland.,d Sanprobi Sp. z o.o. Sp. K , Szczecin , Poland
| | | | - Beata Loniewska
- f Department of Neonatal Diseases , Pomeranian Medical University , Szczecin , Poland
| | - Anastasios Koulaouzidis
- g Centre for Liver and Digestive Disorders , Royal Infirmary of Edinburgh , Edinburgh , United Kingdom
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Xie Q, Pan M, Huang R, Tian X, Tao X, Shah NP, Wei H, Wan C. Short communication: Modulation of the small intestinal microbial community composition over short-term or long-term administration with Lactobacillus plantarum ZDY2013. J Dairy Sci 2016; 99:6913-6921. [DOI: 10.3168/jds.2016-11141] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2016] [Accepted: 05/19/2016] [Indexed: 12/22/2022]
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Patel T, Bhattacharya P, Das S. Gut microbiota: an Indicator to Gastrointestinal Tract Diseases. J Gastrointest Cancer 2016; 47:232-8. [DOI: 10.1007/s12029-016-9820-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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15
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Sources and Bioactive Properties of Conjugated Dietary Fatty Acids. Lipids 2016; 51:377-97. [PMID: 26968402 DOI: 10.1007/s11745-016-4135-z] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2016] [Accepted: 02/17/2016] [Indexed: 12/11/2022]
Abstract
The group of conjugated fatty acids known as conjugated linoleic acid (CLA) isomers have been extensively studied with regard to their bioactive potential in treating some of the most prominent human health malignancies. However, CLA isomers are not the only group of potentially bioactive conjugated fatty acids currently undergoing study. In this regard, isomers of conjugated α-linolenic acid, conjugated nonadecadienoic acid and conjugated eicosapentaenoic acid, to name but a few, have undergone experimental assessment. These studies have indicated many of these conjugated fatty acid isomers commonly possess anti-carcinogenic, anti-adipogenic, anti-inflammatory and immune modulating properties, a number of which will be discussed in this review. The mechanisms through which these bioactivities are mediated have not yet been fully elucidated. However, existing evidence indicates that these fatty acids may play a role in modulating the expression of several oncogenes, cell cycle regulators, and genes associated with energy metabolism. Despite such bioactive potential, interest in these conjugated fatty acids has remained low relative to the CLA isomers. This may be partly attributed to the relatively recent emergence of these fatty acids as bioactives, but also due to a lack of awareness regarding sources from which they can be produced. In this review, we will also highlight the common sources of these conjugated fatty acids, including plants, algae, microbes and chemosynthesis.
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Angelakis E, Lagier JC. Samples and techniques highlighting the links between obesity and microbiota. Microb Pathog 2016; 106:119-126. [PMID: 26828871 DOI: 10.1016/j.micpath.2016.01.024] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Revised: 01/23/2016] [Accepted: 01/28/2016] [Indexed: 12/17/2022]
Abstract
The composition of gut microbiota and its relationship to human health, particularly its links with obesity remain an ongoing challenge for scientists. The current gold standard for exploring human gut microbiota consists of using stool samples and only applying next generations sequencing techniques, which sometimes generate contradictory results. Here, we comprehensively describe nutrient absorption, fat digestion, carbohydrate and protein absorption, demonstrating that absorption of these diverse nutrients occurs mainly in the stomach and small intestine. Indeed, bariatric surgery, including Roux-en-Y, removes part of the upper intestine, resulting in weight loss, while colonic surgery is associated with a stable weight. However, most studies only use stool samples rather than small intestine samples because of the easy with which this can be accessed. Metagenomics studies are associated with several biases such as extraction and primer biases and depth bias, including the more modern platforms. High-throughput culture-dependent techniques, such as culturomics, which uses rapid identification methods such as MALDI-TOF, remain time-consuming, but have demonstrated their complementarity with molecular techniques. In conclusion, we believe that a comprehensive analysis of the relationships between obesity and gut microbiota requires large-scale studies coupling metagenomics and culture-dependent research, in order to analyse both small intestine and stool samples.
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Affiliation(s)
- Emmanouil Angelakis
- Aix-Marseille Université URMITE, UM63, IHU Méditerranée Infection, CNRS 7278, IRD 198, INSERM 1095, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 5, France
| | - Jean-Christophe Lagier
- Aix-Marseille Université URMITE, UM63, IHU Méditerranée Infection, CNRS 7278, IRD 198, INSERM 1095, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 5, France.
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Angelakis E, Armougom F, Carrière F, Bachar D, Laugier R, Lagier JC, Robert C, Michelle C, Henrissat B, Raoult D. A Metagenomic Investigation of the Duodenal Microbiota Reveals Links with Obesity. PLoS One 2015; 10:e0137784. [PMID: 26356733 PMCID: PMC4565581 DOI: 10.1371/journal.pone.0137784] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Accepted: 07/28/2015] [Indexed: 01/16/2023] Open
Abstract
Background Few studies have tested the small intestine microbiota in humans, where most nutrient digestion and absorption occur. Here, our objective was to examine the duodenal microbiota between obese and normal volunteers using metagenomic techniques. Methodology/Principal Findings We tested duodenal samples from five obese and five normal volunteers using 16S rDNA V6 pyrosequencing and Illumina MiSeq deep sequencing. The predominant phyla of the duodenal microbiota were Firmicutes and Actinobacteria, whereas Bacteroidetes were absent. Obese individuals had a significant increase in anaerobic genera (p < 0.001) and a higher abundance of genes encoding Acyl-CoA dehydrogenase (p = 0.0018) compared to the control group. Obese individuals also had a reduced abundance of genes encoding sucrose phosphorylase (p = 0.015) and 1,4-alpha-glucan branching enzyme (p = 0.05). Normal weight people had significantly increased FabK (p = 0.027), and the glycerophospholipid metabolism pathway revealed the presence of phospholipase A1 only in the control group (p = 0.05). Conclusions/Significance The duodenal microbiota of obese individuals exhibit alterations in the fatty acid and sucrose breakdown pathways, probably induced by diet imbalance.
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Affiliation(s)
- Emmanouil Angelakis
- URMITE CNRS-IRD 198 UMR 6236, Aix Marseille Université, Faculté de Médecine, 27 Bd Jean Moulin, 13385, Marseille, France
| | - Fabrice Armougom
- URMITE CNRS-IRD 198 UMR 6236, Aix Marseille Université, Faculté de Médecine, 27 Bd Jean Moulin, 13385, Marseille, France
| | - Frédéric Carrière
- CNRS, Aix Marseille Université, UMR7282 Enzymology at Interfaces and Physiology of Lipolysis, 13009, Marseille, France
| | - Dipankar Bachar
- URMITE CNRS-IRD 198 UMR 6236, Aix Marseille Université, Faculté de Médecine, 27 Bd Jean Moulin, 13385, Marseille, France
| | - René Laugier
- Hepato-gastroenterology Department, Hôpital de la Timone, Marseille, France
| | - Jean-Christophe Lagier
- URMITE CNRS-IRD 198 UMR 6236, Aix Marseille Université, Faculté de Médecine, 27 Bd Jean Moulin, 13385, Marseille, France
| | - Catherine Robert
- URMITE CNRS-IRD 198 UMR 6236, Aix Marseille Université, Faculté de Médecine, 27 Bd Jean Moulin, 13385, Marseille, France
| | - Caroline Michelle
- URMITE CNRS-IRD 198 UMR 6236, Aix Marseille Université, Faculté de Médecine, 27 Bd Jean Moulin, 13385, Marseille, France
| | - Bernard Henrissat
- Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Aix-Marseille Université, 13288, Marseille, France
- Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Didier Raoult
- URMITE CNRS-IRD 198 UMR 6236, Aix Marseille Université, Faculté de Médecine, 27 Bd Jean Moulin, 13385, Marseille, France
- * E-mail:
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Eun CS, Kim BK, Han DS, Kim SY, Kim KM, Choi BY, Song KS, Kim YS, Kim JF. Differences in gastric mucosal microbiota profiling in patients with chronic gastritis, intestinal metaplasia, and gastric cancer using pyrosequencing methods. Helicobacter 2014; 19:407-16. [PMID: 25052961 DOI: 10.1111/hel.12145] [Citation(s) in RCA: 220] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection plays an important role in the early stage of cancer development. However, various bacteria that promote the synthesis of reactive oxygen and nitrogen species may be involved in the later stages. We aimed to determine the microbial composition of gastric mucosa from the patients with chronic gastritis, intestinal metaplasia, and gastric cancer using 454 GS FLX Titanium. METHODS Gastric mucosal biopsy samples were collected from 31 patients during endoscopy. After the extraction of genomic DNA, variable region V5 of the 16S rRNA gene was amplified. PCR products were sequenced using 454 high-throughput sequencer. The composition, diversity, and richness of microbial communities were compared between three groups. RESULTS The composition of H. pylori-containing Epsilonproteobacteria class appeared to be the most prevalent, but the relative increase in the Bacilli class in the gastric cancer group was noticed, resulting in a significant difference compared with the chronic gastritis group. By analyzing the Helicobacter-dominant group at a family level, the relative abundance of Helicobacteraceae family was significantly lower in the gastric cancer group compared with chronic gastritis and intestinal metaplasia groups, while the relative abundance of Streptococcaceae family significantly increased. In a UPGMA clustering of Helicobacter-dominant group based on UniFrac distance, the chronic gastritis group and gastric cancer group were clearly separated, while the intestinal metaplasia group was distributed in between the two groups. The evenness and diversity of gastric microbiota in the gastric cancer group was increased compared with other groups. CONCLUSIONS In Helicobacter predominant patients, the microbial compositions of gastric mucosa from gastric cancer patients are significantly different to chronic gastritis and intestinal metaplasia patients. These alterations of gastric microbial composition may play an important, as-yet-undetermined role in gastric carcinogenesis of Helicobacter predominant patients.
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Affiliation(s)
- Chang Soo Eun
- Department of Internal Medicine, Hanyang University Guri Hospital, Gyeonggi-Do, Korea
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El Aidy S, van den Bogert B, Kleerebezem M. The small intestine microbiota, nutritional modulation and relevance for health. Curr Opin Biotechnol 2014; 32:14-20. [PMID: 25308830 DOI: 10.1016/j.copbio.2014.09.005] [Citation(s) in RCA: 155] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2014] [Revised: 09/18/2014] [Accepted: 09/22/2014] [Indexed: 02/08/2023]
Abstract
The intestinal microbiota plays a profound role in human health and extensive research has been dedicated to identify microbiota aberrations that are associated with disease. Most of this work has been targeting the large intestine and fecal microbiota, while the small intestine microbiota may also have a profound impact on various aspects of the host's physiology, including immune, metabolic and endocrine functions. This review highlights the recent advances made in the study of the human small intestine microbiota. In addition, it describes recent human and animal studies that underpin the importance of this part of the intestine for health of the host organism.
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Affiliation(s)
- Sahar El Aidy
- TI Food and Nutrition, Wageningen, The Netherlands; Laboratory of Neurogastroenterology, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Industrial Biotechnology, Genetic Engineering and Biotechnology Research Institute, Sadat City University, Sadat City, Egypt
| | - Bartholomeus van den Bogert
- TI Food and Nutrition, Wageningen, The Netherlands; Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
| | - Michiel Kleerebezem
- TI Food and Nutrition, Wageningen, The Netherlands; Host-Microbe Interactomics Group, Wageningen University, Wageningen, The Netherlands; NIZO Food Research, Ede, The Netherlands.
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Intestinal alkaline phosphatase prevents antibiotic-induced susceptibility to enteric pathogens. Ann Surg 2014; 259:715-22. [PMID: 23598380 DOI: 10.1097/sla.0b013e31828fae14] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To determine the efficacy of oral supplementation of the gut enzyme intestinal alkaline phosphatase (IAP) in preventing antibiotic-associated infections from Salmonella enterica serovar Typhimurium (S. Typhimurium) and Clostridium difficile. BACKGROUND The intestinal microbiota plays a pivotal role in human health and well-being. Antibiotics inherently cause dysbiosis, an imbalance in the number and composition of intestinal commensal bacteria, which leads to susceptibility to opportunistic bacterial infections. Previously, we have shown that IAP preserves the normal homeostasis of intestinal microbiota and that oral supplementation with calf IAP (cIAP) rapidly restores the normal gut flora. We hypothesized that oral IAP supplementation would protect against antibiotic-associated bacterial infections. METHODS C57BL/6 mice were treated with antibiotic(s) ± cIAP in the drinking water, followed by oral gavage of S. Typhimurium or C. difficile. Mice were observed for clinical conditions and mortality. After a defined period of time, mice were killed and investigated for hematological, inflammatory, and histological changes. RESULTS We observed that oral supplementation with cIAP during antibiotic treatment protects mice from infections with S. Typhimurium as well as with C. difficile. Animals given IAP maintained their weight, had reduced clinical severity and gut inflammation, and showed improved survival. CONCLUSIONS Oral IAP supplementation protected mice from antibiotic-associated bacterial infections. We postulate that oral IAP supplementation could represent a novel therapy to protect against antibiotic-associated diarrhea (AAD), C. difficile-associated disease (CDAD), and other enteric infections in humans.
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Role of the lower and upper intestine in the production and absorption of gut microbiota-derived PUFA metabolites. PLoS One 2014; 9:e87560. [PMID: 24475308 PMCID: PMC3903770 DOI: 10.1371/journal.pone.0087560] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2013] [Accepted: 12/21/2013] [Indexed: 01/01/2023] Open
Abstract
In vitro studies have suggested that isolated gut bacteria are able to metabolize PUFA into CLA (conjugated linoleic acids) and CLnA (conjugated linolenic acids). However, the bioavailability of fatty acid metabolites produced in vivo by the gut microbes remains to be studied. Therefore, we measured intestinal concentration and plasma accumulation of bacterial metabolites produced from dietary PUFA in mice, first injected with a lipoprotein lipase inhibitor, then force-fed with either sunflower oil (200 µl) rich in n-6 PUFA or linseed oil (200 µl) rich in n-3 PUFA. The greatest production of bacterial metabolites was observed in the caecum and colon, and at a much lesser extent in the jejunum and ileum. In the caecal content, CLA proportions were higher in sunflower oil force-fed mice whereas CLnA proportions were higher in linseed oil force-fed mice. The accumulation of the main metabolites (CLA cis-9,trans-11-18:2 and CLnA cis-9,trans-11,cis-15-18:3) in the caecal tissue was not associated with their increase in the plasma, therefore suggesting that, if endogenously produced CLA and CLnA have any biological role in host metabolism regulation, their effect would be confined at the intestinal level, where the microbiota is abundant.
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Barra AA, Silva ALD, Rena CDL, Furtado MCV, Ferreira AB, Nagen M, Freitas FDS. Analysis of the diversity of the intestinal microbiota of rats subjected to resection of the ileocecal valve and creation of artificial sphincter. Rev Col Bras Cir 2014; 39:521-8. [PMID: 23348650 DOI: 10.1590/s0100-69912012000600013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2012] [Accepted: 07/20/2012] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVE To analyze, through molecular biology, the diversity of the intestinal microbiota before and after resection of the ileocecal junction and reconstruction of intestinal transit with and without the creation of a neosphincter. METHODS Fourteen Wistar rats were divided into two groups: Group A (n = 7), submitted to resection of the ileocecal valve and end-to-end, single-layer ileocolic anastomosis; and Group B (n = 7) with resection of the ileocecal valve and end-to-end, single-layer ileocolic anastomosis followed by construction of an artificial sphincter. Intraluminal contents were collected from both groups. The animals were reoperated 20 days after the first procedure, with new collection of intraluminal contents of the ileum and colon. From the samples collected, DNA was extracted for PCR-DGGE. The electrophoretic banding patterns generated in the reaction were analyzed for similarities and diversities of the microbiota. RESULTS The diversity of microorganisms was larger and in more samples when collected from the ileum than from the colon. The group with the neosphincter showed the highest variation in the colon, from 2.11 to 2.93. In three animals from each group was established comparing the similarity and not resembled the control. CONCLUSION ileocecal resection led to changes in ileal microbiota and, with the creation of new sphincter, the changes were even greater.
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Affiliation(s)
- Angela Aparecida Barra
- Post-Graduate Program in Applied Sciences to Surgery and Ophthalmology, Faculty of Medicine, Federal University of MinasGerais-MG, Brazil.
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Chiba M, Ono I, Wakamatsu H, Wada I, Suzuki K. Diffuse gastroduodenitis associated with ulcerative colitis: treatment by infliximab. Dig Endosc 2013; 25:622-5. [PMID: 24164601 DOI: 10.1111/j.1443-1661.2012.01398.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2012] [Accepted: 09/06/2012] [Indexed: 01/21/2023]
Abstract
Diffuse gastroduodenitis resembling ulcerative colitis in respect to macro- and microscopic findings occurs in ulcerative colitis, although it is rare. Reports of gastroduodenitis associated with ulcerative colitis treated with infliximab are rare. A 58-year-old man had tarry stool in March 2011. He had a history of ulcerative colitis that was diagnosed in 1984. He underwent subtotal colectomy in 1991. Endoscopy and radiography revealed diffuse friable mucosa throughout the duodenum and an ulcer in the middle of the descending portion, resulting in a narrow portion.In the stomach, numerous small aphthae were observed in the antrum. Biopsy specimens of the duodenum and antrum showed marked inflammatory cell infiltration in both areas and cryptitis in the duodenum. Standard induction therapy of infliximab was started in April. The ulcer in the descending portion became a scar without diffuse mucosal friability in September 2011.
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Affiliation(s)
- Mitsuro Chiba
- Division of Gastroenterology, Nakadori General Hospital
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Abstract
The clinical manifestations of cystic fibrosis (CF) result from dysfunction of the cystic fibrosis transmembrane regulator protein (CFTR). The majority of people with CF have a limited life span as a consequence of CFTR dysfunction in the respiratory tract. However, CFTR dysfunction in the gastrointestinal (GI) tract occurs earlier in ontogeny and is present in all patients, regardless of genotype. The same pathophysiologic triad of obstruction, infection, and inflammation that causes disease in the airways also causes disease in the intestines. This article describes the effects of CFTR dysfunction on the intestinal tissues and the intraluminal environment. Mouse models of CF have greatly advanced our understanding of the GI manifestations of CF, which can be directly applied to understanding CF disease in humans.
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Affiliation(s)
- Robert C De Lisle
- Anatomy and Cell Biology, University of Kansas School of Medicine, Kansas City, Kansas 66160
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Exclusive elemental diet impacts on the gastrointestinal microbiota and improves symptoms in patients with chronic pouchitis. J Crohns Colitis 2013; 7:460-6. [PMID: 22857825 DOI: 10.1016/j.crohns.2012.07.009] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2012] [Revised: 06/24/2012] [Accepted: 07/08/2012] [Indexed: 02/08/2023]
Abstract
BACKGROUND Treatment resistant chronic pouchitis causes significant morbidity. Elemental diet is effective treatment for Crohn's disease. Since pouchitis shares some similarities to Crohn's disease we hypothesised that elemental diet may be an effective treatment. METHOD Seven pouchitis patients (with ulcerative colitis) were studied. All had active pouchitis with a pouch disease activity index (PDAI) ≥7. Exclusion criteria were recent NSAIDs, antibiotics or probiotics. Sufficient elemental diet to achieve energy requirements was provided. Flexible-pouchoscopy was performed, and the Cleveland Global Quality of Life score (CGQoL), Pouch Disease Activity Index (PDAI) and BMI were recorded at baseline and following 28 days of elemental diet. Faecal samples were also collected at these time points and analysed for major bacterial groups using culture independent fluorescence in situ hybridisation. Data were analysed using Wilcoxon's signed-rank test. RESULTS Following 28 days of exclusive elemental diet, median stool frequency decreased from 12 to 6 per day (p=0.028), median clinical PDAI decreased from 4 to 1 (p=0.039). There was no significant difference in quality of life scores or PDAI before and following treatment. There was a trend towards an increase in the concentration of Clostridium coccoides-Eubacterium rectale (median 7.9 to 8.5 log₁₀/g, p=0.08) following exclusive elemental diet. CONCLUSION Treatment with four weeks elemental diet appeared to improve the symptoms of chronic pouchitis in some patients but is not an effective strategy for inducing remission. Although a potential symptom modifier, elemental diet cannot be recommended for the routine treatment of active pouchitis.
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Zanello M, Vincenzi M, Di Mauro L, Gualdani S. Gut and sepsis: Victim of circumstance or prime mover. TRENDS IN ANAESTHESIA AND CRITICAL CARE 2013. [DOI: 10.1016/j.tacc.2013.03.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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van den Bogert B, Erkus O, Boekhorst J, de Goffau M, Smid EJ, Zoetendal EG, Kleerebezem M. Diversity of human small intestinal Streptococcus and Veillonella populations. FEMS Microbiol Ecol 2013; 85:376-88. [PMID: 23614882 DOI: 10.1111/1574-6941.12127] [Citation(s) in RCA: 117] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2012] [Revised: 03/15/2013] [Accepted: 03/25/2013] [Indexed: 01/08/2023] Open
Abstract
Molecular and cultivation approaches were employed to study the phylogenetic richness and temporal dynamics of Streptococcus and Veillonella populations in the small intestine. Microbial profiling of human small intestinal samples collected from four ileostomy subjects at four time points displayed abundant populations of Streptococcus spp. most affiliated with S. salivarius, S. thermophilus, and S. parasanguinis, as well as Veillonella spp. affiliated with V. atypica, V. parvula, V. dispar, and V. rogosae. Relative abundances varied per subject and time of sampling. Streptococcus and Veillonella isolates were cultured using selective media from ileostoma effluent samples collected at two time points from a single subject. The richness of the Streptococcus and Veillonella isolates was assessed at species and strain level by 16S rRNA gene sequencing and genetic fingerprinting, respectively. A total of 160 Streptococcus and 37 Veillonella isolates were obtained. Genetic fingerprinting differentiated seven Streptococcus lineages from ileostoma effluent, illustrating the strain richness within this ecosystem. The Veillonella isolates were represented by a single phylotype. Our study demonstrated that the small intestinal Streptococcus populations displayed considerable changes over time at the genetic lineage level because only representative strains of a single Streptococcus lineage could be cultivated from ileostoma effluent at both time points.
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The duodenal microbiota composition of adult celiac disease patients is associated with the clinical manifestation of the disease. Inflamm Bowel Dis 2013; 19:934-41. [PMID: 23478804 DOI: 10.1097/mib.0b013e31828029a9] [Citation(s) in RCA: 141] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Celiac disease is classically manifested in the gastrointestinal (GI) tract but extraintestinal symptoms, such as dermatitis herpetiformis (DH), are also common. Besides several well-known shared genetic risk factors and an environmental trigger, gliadin, factors determining the clinical outcome of the disease are not known. In this study, the role of duodenal microbiota in the celiac disease outcome was studied by analyzing mucosa-associated microbiota in celiac disease patients with a variety of intestinal and extraintestinal symptoms. METHODS Microbiota in duodenal biopsy samples obtained from 33 patients with celiac disease with GI, DH, anemia, or mixed symptoms, as well as screen-detected asymptomatic celiac disease and 18 control subjects were analyzed using PCR denaturing gradient gel electrophoresis and a subset of samples additionally by the 16S ribosomal RNA gene sequencing. RESULTS The composition and diversity of mucosal microbiota was associated with the manifestation of celiac disease when analyzed using PCR denaturing gradient gel electrophoresis and the 16S ribosomal RNA gene sequencing. The patients with celiac disease with GI symptoms or anemia had lower microbial diversity than those with DH. Moreover, the patients with GI symptoms had different intestinal microbiota composition and structure, dominated by Proteobacteria, in comparison to those with DH or control subjects (patients with dyspepsia). The relatively similar intestinal microbiota composition in the control subjects and those with DH was characterized by the high abundance of Firmicutes. CONCLUSIONS The two common outcomes of celiac disease, classical GI and extraintestinal manifestations, had marked differences on the diversity and composition of intestinal microbiota. This association suggested that intestinal microbiota may have a role in the manifestation of the disease.
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Wang ZK, Yang YS. Upper gastrointestinal microbiota and digestive diseases. World J Gastroenterol 2013; 19:1541-1550. [PMID: 23539678 PMCID: PMC3602471 DOI: 10.3748/wjg.v19.i10.1541] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2012] [Revised: 01/21/2013] [Accepted: 01/24/2013] [Indexed: 02/06/2023] Open
Abstract
Metagenomics which combines the power of genomics, bioinformatics, and systems biology, provide new access to the microbial world. Metagenomics permit the genetic analysis of complex microbial populations without requiring prior cultivation. Through the conceptual innovations in metagenomics and the improvements in DNA high-throughput sequencing and bioinformatics analysis technology, gastrointestinal microbiology has entered the metagenomics era and become a hot topic worldwide. Human microbiome research is underway, however, most studies in this area have focused on the composition and function of the intestinal microbiota and the relationship between intestinal microbiota and metabolic diseases (obesity, diabetes, metabolic syndrome, etc.) and intestinal disorders [inflammatory bowel disease, colorectal cancer, irritable bowel syndrome (IBS), etc.]. Few investigations on microbiota have been conducted within the upper gastrointestinal tract (esophagus, stomach and duodenum). The upper gastrointestinal microbiota is essential for several gastrointestinal illnesses, including esophagitis, Barrett’s esophagus, and esophageal carcinoma, gastritis and gastric cancer, small intestinal bacterial overgrowth, IBS and celiac disease. However, the constitution and diversity of the microbiota in different sections of the upper gastrointestinal tract under health and various disease states, as well as the function of microbiota in the pathogenesis of various digestive diseases are still undefined. The current article provides an overview of the recent findings regarding the relationship between upper gastrointestinal microbiota and gastrointestinal diseases; and discusses the study limitations and future directions of upper gastrointestinal microbiota research.
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Nickerson KP, McDonald C. Crohn's disease-associated adherent-invasive Escherichia coli adhesion is enhanced by exposure to the ubiquitous dietary polysaccharide maltodextrin. PLoS One 2012; 7:e52132. [PMID: 23251695 PMCID: PMC3520894 DOI: 10.1371/journal.pone.0052132] [Citation(s) in RCA: 92] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2012] [Accepted: 11/15/2012] [Indexed: 12/12/2022] Open
Abstract
Crohn's disease (CD) is associated with intestinal dysbiosis evidenced by an altered microbiome forming thick biofilms on the epithelium. Additionally, adherent-invasive E. coli (AIEC) strains are frequently isolated from ileal lesions of CD patients indicating a potential role for these strains in disease pathogenesis. The composition and characteristics of the host microbiome are influenced by environmental factors, particularly diet. Polysaccharides added to food as emulsifiers, stabilizers or bulking agents have been linked to bacteria-associated intestinal disorders. The escalating consumption of polysaccharides in Western diets parallels an increased incidence of CD during the latter 20th century. In this study, the effect of a polysaccharide panel on adhesiveness of the CD-associated AIEC strain LF82 was analyzed to determine if these food additives promote disease-associated bacterial phenotypes. Maltodextrin (MDX), a polysaccharide derived from starch hydrolysis, markedly enhanced LF82 specific biofilm formation. Biofilm formation of multiple other E. coli strains was also promoted by MDX. MDX-induced E. coli biofilm formation was independent of polysaccharide chain length indicating a requirement for MDX metabolism. MDX exposure induced type I pili expression, which was required for MDX-enhanced biofilm formation. MDX also increased bacterial adhesion to human intestinal epithelial cell monolayers in a mechanism dependent on type 1 pili and independent of the cellular receptor CEACAM6, suggesting a novel mechanism of epithelial cell adhesion. Analysis of mucosa-associated bacteria from individuals with and without CD showed increased prevalence of malX, a gene essential for MDX metabolism, uniquely in the ileum of CD patients. These findings demonstrate that the ubiquitous dietary component MDX enhances E. coli adhesion and suggests a mechanism by which Western diets rich in specific polysaccharides may promote dysbiosis of gut microbes and contribute to disease susceptibility.
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Affiliation(s)
- Kourtney P. Nickerson
- Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America
| | - Christine McDonald
- Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America
- * E-mail:
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de Vos WM, de Vos EAJ. Role of the intestinal microbiome in health and disease: from correlation to causation. Nutr Rev 2012; 70 Suppl 1:S45-56. [PMID: 22861807 DOI: 10.1111/j.1753-4887.2012.00505.x] [Citation(s) in RCA: 286] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Recorded observations indicating an association between intestinal microbes and health are long-standing in terms of specific diseases, but emerging high-throughput technologies that characterize microbial communities in the intestinal tract are suggesting new roles for the supposedly normal microbiome. This review considers the nature of the evidence supporting a relationship between the microbiota and the predisposition to disease as associative, correlative, or causal. Altogether, indirect or associative support currently dominates the evidence base, which now suggests that the intestinal microbiome can be linked to a growing number of over 25 diseases or syndromes. While only a handful of cause-and-effect studies have been performed, this form of evidence is increasing. The results of such studies are expected to be useful in monitoring disease development, in providing a basis for personalized treatments, and in indicating future therapeutic avenues.
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Affiliation(s)
- Willem M de Vos
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
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Oh PL, Martínez I, Sun Y, Walter J, Peterson DA, Mercer DF. Characterization of the ileal microbiota in rejecting and nonrejecting recipients of small bowel transplants. Am J Transplant 2012; 12:753-62. [PMID: 22152019 DOI: 10.1111/j.1600-6143.2011.03860.x] [Citation(s) in RCA: 122] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Small bowel transplantation can be a life-preserving procedure for patients with irreversible intestinal failure. Allograft rejection remains a major source of morbidity and mortality and its accurate diagnosis and treatment are critical. In this study, we used pyrosequencing of 16S ribosomal RNA gene tags to compare the composition of the ileal microbiota present during nonrejection, prerejection and active rejection states in small bowel transplant patients. During episodes of rejection, the proportions of phylum Firmicutes (p < 0.001) and the order Lactobacillales (p < 0.01) were significantly decreased, while those of the phylum Proteobacteria, especially the family Enterobacteriaceae, were significantly increased (p < 0.005). Receiver-operating characteristic analysis revealed that relative proportions of several bacterial taxa in ileal effluents and especially Firmicutes, could be used to discriminate between nonrejection and active rejection. In conclusion, the findings obtained during this study suggest that small bowel transplant rejection is associated with changes in the microbial populations in ileal effluents and support microbiota profiling as a potential diagnostic biomarker of rejection. Future studies should investigate if the dysbiosis that we observed is a cause or a consequence of the rejection process.
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Affiliation(s)
- P L Oh
- Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, USA
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