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Chen J, Mou L, Wang L, Wu G, Dai X, Chen Q, Zhang J, Luo X, Xu F, Zhang M, Duan Y, Pang H, Wang Y, Cai Y, Tan Z. Mixed Bacillus subtilis and Lactiplantibacillus plantarum-fermented feed improves gut microbiota and immunity of Bamei piglet. Front Microbiol 2024; 15:1442373. [PMID: 39268530 PMCID: PMC11390403 DOI: 10.3389/fmicb.2024.1442373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 08/02/2024] [Indexed: 09/15/2024] Open
Abstract
Antibiotics are widely used in the breeding production of Bamei pigs, affecting the quality and safety of pork and causing enormous harm to human health, the environment, and public health. The use of probiotic fermented feed to replace antibiotic feed is one of the solutions, which has the potential to improve the intestinal microbiota, promote animal growth, and enhance immunity. The purpose of this study was to evaluate the effect of fermented feed with Lactiplantibacillus (L.) plantarum QP28-1a or Bacillus (B.) subtilis QB8a on feed, growth performance, gut microbiota, and immunity of weaned piglets. A total of 60 freshly weaned piglets from the Tibetan Plateau were randomly divided into five groups and fed basal feed, L. plantarum fermented feed, B. subtilis fermented feed, mixed fermented feed, and antibiotic fermented feed for 60 days, respectively. The results showed fermented feed supplemented with L. plantarum QP28-1a or B. subtilis QB8a significantly lowered the pH of the feed (P < 0.05), produced lactic acid and acetic acid, inhibited the growth of harmful bacteria in the feed, and reduced the feed conversion rate in the group fed mixed fermented feed (P < 0.05). The fermented feed increased the α-diversity and prominently altered the β-diversity of the intestinal microbiota, increasing the relative abundance of beneficial bacteria such as Lactobacillus and Turicibacter and decreasing the relative abundance of conditional pathogens such as Streptococcus and Clostridium, improving the intestinal microbiota of the Bamei piglets. Notably, the mixed fermented feed improved the immunity of Bamei piglets by modulating the production of pro-inflammatory cytokines, anti-inflammatory cytokines, and inflammatory-related signaling pathways. Spearman's correlation analysis revealed that the increased expression of immune-related cytokines may be associated with a significant enrichment of Lactobacillus, Prevotellaceae, Erysipelotrichaceae, and Ruminococcaceae in the gut. In conclusion, the probiotic fermented feed maintained an acidic environment conducive to suppressing pathogens, reduced the feed conversion ratio, optimized the intestinal microbiota, improved immunity, and alleviated intestinal inflammation that may be caused by weaning, demonstrating the excellent application prospects of L. plantarum QP28-1a and B. subtilis QB8a fermented feed in the feeding of Bamei piglets.
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Affiliation(s)
- Jun Chen
- Henan Key Laboratory of Ion-Beam Green Agriculture Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, China
| | - Liyu Mou
- Henan Key Laboratory of Ion-Beam Green Agriculture Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, China
| | - Lei Wang
- Plateau Livestock Genetic Resources Protection and Innovative Utilization Key Laboratory of Qinghai Province, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Qinghai Academy of Animal Science and Veterinary Medicine, Qinghai University, Xining, China
| | - Guofang Wu
- Plateau Livestock Genetic Resources Protection and Innovative Utilization Key Laboratory of Qinghai Province, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Qinghai Academy of Animal Science and Veterinary Medicine, Qinghai University, Xining, China
| | - Ximei Dai
- Laboratory of Zhongyuan Light, School of Physics, Zhengzhou University, Zhengzhou, China
| | - Qiufang Chen
- Laboratory of Zhongyuan Light, School of Physics, Zhengzhou University, Zhengzhou, China
| | - Jianbo Zhang
- Plateau Livestock Genetic Resources Protection and Innovative Utilization Key Laboratory of Qinghai Province, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Qinghai Academy of Animal Science and Veterinary Medicine, Qinghai University, Xining, China
| | - Xuan Luo
- Plateau Livestock Genetic Resources Protection and Innovative Utilization Key Laboratory of Qinghai Province, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Qinghai Academy of Animal Science and Veterinary Medicine, Qinghai University, Xining, China
| | - Fafang Xu
- Bamei Pig Original Breeding Base of Huzhu County, Huzhou, China
| | - Miao Zhang
- Henan Key Laboratory of Ion-Beam Green Agriculture Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, China
| | - Yaoke Duan
- Henan Key Laboratory of Ion-Beam Green Agriculture Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, China
| | - Huili Pang
- Henan Key Laboratory of Ion-Beam Green Agriculture Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, China
| | - Yanping Wang
- Henan Key Laboratory of Ion-Beam Green Agriculture Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, China
| | - Yimin Cai
- Henan Key Laboratory of Ion-Beam Green Agriculture Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, China
| | - Zhongfang Tan
- Henan Key Laboratory of Ion-Beam Green Agriculture Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, China
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Zhang CE, Yu XH, Cui YT, Wang HJ, Chen X, Ma XJ, Li H, Su JR, Ma ZJ, Huang LQ. Shengjiang Xiexin Decoction ameliorates antibiotic-associated diarrhea by altering the gut microbiota and intestinal metabolic homeostasis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 113:154737. [PMID: 36905867 DOI: 10.1016/j.phymed.2023.154737] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 02/24/2023] [Accepted: 02/28/2023] [Indexed: 06/18/2023]
Abstract
BACKGROUND Antibiotic-associated diarrhea (AAD) has had a significant increase in the last years, with limited available effective therapies. Shengjiang Xiexin Decoction (SXD), a classic traditional Chinese medicine formula for treating diarrhea, is a promising alternative for reducing the incidence of AAD. PURPOSE This study aimed to explore the therapeutic effect of SXD on AAD and to investigate its potential therapeutic mechanism by integrated analysis of the gut microbiome and intestinal metabolic profile. METHODS 16S rRNA sequencing analysis of the gut microbiota and untargeted-metabolomics analysis of feces were performed. The mechanism was further explored by fecal microbiota transplantation (FMT). RESULTS SXD could effectively ameliorate AAD symptoms and restore intestinal barrier function. In addition, SXD could significantly improve the diversity of the gut microbiota and accelerate the recovery of the gut microbiota. At the genus level, SXD significantly increased the relative abundance of Bacteroides spp (p < 0.01) and decreased the relative abundance of Escherichia_Shigela spp (p < 0.001). Untargeted metabolomics showed that SXD significantly improved gut microbiota and host metabolic function, particularly bile acid metabolism and amino acid metabolism. CONCLUSION This study demonstrated that SXD could extensively modulate the gut microbiota and intestinal metabolic homeostasis to treat AAD.
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Affiliation(s)
- Cong-En Zhang
- Department of Pharmacy, Beijing Friendsip Hospital, Capital Medical University, 100050, Beijing, China
| | - Xiao-Hong Yu
- Department of Pharmacy, Beijing Friendsip Hospital, Capital Medical University, 100050, Beijing, China
| | - Yu-Tao Cui
- Department of Pharmacy, Beijing Friendsip Hospital, Capital Medical University, 100050, Beijing, China
| | - Huan-Jun Wang
- Department of Pharmacy, Beijing Friendsip Hospital, Capital Medical University, 100050, Beijing, China
| | - Xi Chen
- Department of Pharmacy, Beijing Friendsip Hospital, Capital Medical University, 100050, Beijing, China
| | - Xiao-Jing Ma
- Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Hui Li
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Jian-Rong Su
- Clinical Laboratory Center, Beijing Friendship Hospital, Capital Medical University, 100050, Beijing, China
| | - Zhi-Jie Ma
- Department of Pharmacy, Beijing Friendsip Hospital, Capital Medical University, 100050, Beijing, China.
| | - Lu-Qi Huang
- Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
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Dempsey E, Corr SC. Lactobacillus spp. for Gastrointestinal Health: Current and Future Perspectives. Front Immunol 2022; 13:840245. [PMID: 35464397 PMCID: PMC9019120 DOI: 10.3389/fimmu.2022.840245] [Citation(s) in RCA: 206] [Impact Index Per Article: 68.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 03/15/2022] [Indexed: 11/13/2022] Open
Abstract
In recent decades, probiotic bacteria have become increasingly popular as a result of mounting scientific evidence to indicate their beneficial role in modulating human health. Although there is strong evidence associating various Lactobacillus probiotics to various health benefits, further research is needed, in particular to determine the various mechanisms by which probiotics may exert these effects and indeed to gauge inter-individual value one can expect from consuming these products. One must take into consideration the differences in individual and combination strains, and conditions which create difficulty in making direct comparisons. The aim of this paper is to review the current understanding of the means by which Lactobacillus species stand to benefit our gastrointestinal health.
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Affiliation(s)
- Elaine Dempsey
- Trinity Biomedical Science Institute, School of Biochemistry and Immunology, Trinity College, Dublin, Ireland.,Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College, Dublin, Ireland
| | - Sinéad C Corr
- Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College, Dublin, Ireland.,APC Microbiome Ireland, University College Cork, Cork, Ireland
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Yogurt fortified with vitamins and probiotics impacts the frequency of upper respiratory tract infections but not gut microbiome: A multicenter double-blind placebo controlled randomized study. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104572] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
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Klein M, Angstwurm K, Esser S, Hahn K, Maschke M, Scheithauer S, Schoefer H, Sturzenegger M, Wildemann B, Weber J. German guidelines on the diagnosis and treatment of neurosyphilis. Neurol Res Pract 2020; 2:33. [PMID: 33225223 PMCID: PMC7669305 DOI: 10.1186/s42466-020-00081-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 07/22/2020] [Indexed: 12/17/2022] Open
Abstract
Introduction In view of the importance of neurosyphilis and the difficulties encountered in diagnosing it, the S1 guideline "Neurosyphilis" has been published by the German Society for Neurology (DGN) in accordance with the stipulations of the Association of the Scientific Medical Societies in Germany (AWMF). The present article is an abridged translation of that German guideline. Main recommendations (a) Neurosyphilis can manifest as early neurosyphilis (meningitis, meningovascular neurosyphilis or syphilitic gummas) or late neurosyphilis (tabes dorsalis, general paresis). (b) The following diagnostic criteria help to establish the presence of probable neurosyphilis (always point iv, accompanied by any two of points i to iii): (i) subacute or chronic neuro-psychiatric symptoms; (ii) increased cerebrospinal fluid (CSF) cell count or signs of blood-CSF barrier disruption; (iii) positive effect of anti-neurosyphilis antibiotic therapy on clinical course and CSF findings; (iv) positive TPHA/TPPA or FTA test in serum. (c) The diagnosis of neurosyphilis is confirmed by the subsequent detection of intrathecal production of antibodies against Treponema pallidum. (d) In neurosyphilis, treatment with intravenous penicillin or ceftriaxone for 14 days is recommended. (e) The following parameters can be used to assess a therapeutic effect: clinical findings, serum VDRL, and CSF cell count. Conclusion The German guideline on the diagnosis and treatment of neurosyphilis is a practical tool to support clinicians in diagnosing and treating patients with neurosyphilis. This article is an abridged translation of this guideline (Klein MW, J.; Angstwurm, K.; Esser, S.; Hahn, K.; Matschke, M.; Scheithauer, S.; Schoefer, H.; Sturzenegger, M.; Wildemann, B. Neurosyphilis, S1-Leitlinie. Deutsche Gesellschaft für Neurologie, Leitlinien für Diagnostik und Thearpie in der Neurologie 2020).
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Affiliation(s)
- Matthias Klein
- Department of Neurology, LMU Klinikum Muenchen, Marchioninistr. 15, 81377 Munich, Germany
| | - Klemens Angstwurm
- Department of Neurology, Universitaetsklinik Regensburg, Universitaetsstr. 84, 93042 Regensburg, Germany
| | - Stefan Esser
- Department of Dermatology, Universitaetsklinikum Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Kathrin Hahn
- Department of Neurology, Charite Berlin, Chariteplatz 1, 10117 Berlin, Germany
| | - Matthias Maschke
- Department of Neurology, Krankenhaus der Barmherzigen Brueder Trier, Nordallee 1, 54292 Trier, Germany
| | - Simone Scheithauer
- Institute for Hygiene and Infectiology, Universitaet Goettingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany
| | - Helmut Schoefer
- Dr. Horst Schmidt Kliniken, Aukamm-Allee 33, 65191 Wiesbaden, Germany
| | - Matthias Sturzenegger
- Department of Neurology, Inselspital Bern, Freiburgstrasse 15, 3010 Bern, Switzerland
| | - Brigitte Wildemann
- Department of Neurology, Universitaetsklinik Heidelberg, Im Neuenheimer Feld 672, 69120 Heidelberg, Germany
| | - Jörg Weber
- Department of Neurology, Klinikum Klagenfurt, Feschnigstraße 11, 9020 Klagenfurt am Wörthsee, Austria
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van Zyl WF, Deane SM, Dicks LM. Molecular insights into probiotic mechanisms of action employed against intestinal pathogenic bacteria. Gut Microbes 2020; 12:1831339. [PMID: 33112695 PMCID: PMC7595611 DOI: 10.1080/19490976.2020.1831339] [Citation(s) in RCA: 155] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Gastrointestinal (GI) diseases, and in particular those caused by bacterial infections, are a major cause of morbidity and mortality worldwide. Treatment is becoming increasingly difficult due to the increase in number of species that have developed resistance to antibiotics. Probiotic lactic acid bacteria (LAB) have considerable potential as alternatives to antibiotics, both in prophylactic and therapeutic applications. Several studies have documented a reduction, or prevention, of GI diseases by probiotic bacteria. Since the activities of probiotic bacteria are closely linked with conditions in the host's GI-tract (GIT) and changes in the population of enteric microorganisms, a deeper understanding of gut-microbial interactions is required in the selection of the most suitable probiotic. This necessitates a deeper understanding of the molecular capabilities of probiotic bacteria. In this review, we explore how probiotic microorganisms interact with enteric pathogens in the GIT. The significance of probiotic colonization and persistence in the GIT is also addressed.
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Affiliation(s)
- Winschau F. van Zyl
- Department of Microbiology, Stellenbosch University, Stellenbosch, South Africa
| | - Shelly M. Deane
- Department of Microbiology, Stellenbosch University, Stellenbosch, South Africa
| | - Leon M.T. Dicks
- Department of Microbiology, Stellenbosch University, Stellenbosch, South Africa,CONTACT Leon M.T. Dicks; Department of Microbiology; Stellenbosch University, Stellenbosch7602, South Africa
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Kluijfhout S, Trieu TV, Vandenplas Y. Efficacy of the Probiotic Probiotical Confirmed in Acute Gastroenteritis. Pediatr Gastroenterol Hepatol Nutr 2020; 23:464-471. [PMID: 32953642 PMCID: PMC7481057 DOI: 10.5223/pghn.2020.23.5.464] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Revised: 04/16/2020] [Accepted: 04/21/2020] [Indexed: 01/26/2023] Open
Abstract
PURPOSE Some probiotic strains reduce the duration of acute diarrhea. Because of strain and product specificity, each product needs to be supported by clinical data. This study aimed to test the efficacy of the synbiotic food supplement Probiotical (Streptococcus thermophilus, Lactobacillus rhamnosus, Lactobacillus acidophilus, Bifidobacterium lactis, Bifidobacterium infantis, fructo-oligosaccharides) in children with acute gastroenteritis of likely infectious origin. The primary endpoint was the number of children with normal stool consistency during the treatment duration. METHODS A total of 46 children (aged 3.6 months to 12 years) with acute gastroenteritis that started less than 48 hours prior to their visit at a hospital-based emergency department were included in this prospective, randomized, placebo-controlled trial. All children were treated with oral rehydration solution and placebo (n=20) or the test product (n=26). RESULTS Significantly more children had a normal stool consistency on days 1 and 2 in the probiotic group: 5 children (20%) on day 1 in the probiotic group compared with none in the placebo group (p=0.046). On day 2, 11 children in the probiotic group (46%) and 3 (16%) in the placebo group (p=0.024) had a normal stool consistency. The mean duration of diarrhea was shorter in the probiotic group compared with that in the placebo group (3.04±1.36 vs. 4.20±1.34 days) (p=0.018). CONCLUSION The test product was shown to normalize stool consistency significantly more rapidly than the placebo. These data confirm the findings from a previous study in a larger group of children performed in a primary healthcare setting.
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Affiliation(s)
- Sandra Kluijfhout
- KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium
| | - Thanh-Van Trieu
- CHL KannerKlinik, Urgences Pédiatriques, Luxembourg, Luxembourg
| | - Yvan Vandenplas
- KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium
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Guo Q, Goldenberg JZ, Humphrey C, El Dib R, Johnston BC, Cochrane IBD Group. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev 2019; 4:CD004827. [PMID: 31039287 PMCID: PMC6490796 DOI: 10.1002/14651858.cd004827.pub5] [Citation(s) in RCA: 109] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Antibiotics alter the microbial balance commonly resulting in antibiotic-associated diarrhea (AAD). Probiotics may prevent AAD via providing gut barrier, restoration of the gut microflora, and other potential mechanisms of action. OBJECTIVES The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children. SEARCH METHODS MEDLINE, Embase, CENTRAL, CINAHL, and the Web of Science (inception to 28 May 2018) were searched along with registers including the ISRCTN and Clinicaltrials.gov. We also searched the NICE Evidence Services database as well as reference lists from relevant articles. SELECTION CRITERIA Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the incidence of diarrhea secondary to antibiotic use were considered for inclusion. DATA COLLECTION AND ANALYSIS Study selection, data extraction, and risk of bias assessment were conducted independently by two authors. Dichotomous data (incidence of AAD, adverse events) were combined using a pooled risk ratio (RR) or risk difference (RD), and continuous data (mean duration of diarrhea) as mean difference (MD), along with corresponding 95% confidence interval (95% CI). We calculated the number needed to treat for an additional beneficial outcome (NNTB) where appropriate. For studies reporting on microbiome characteristics using heterogeneous outcomes, we describe the results narratively. The certainty of the evidence was evaluated using GRADE. MAIN RESULTS Thirty-three studies (6352 participants) were included. Probiotics assessed included Bacillus spp., Bifidobacterium spp., Clostridium butyricum, Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., orStreptococcus spp., alone or in combination. The risk of bias was determined to be high in 20 studies and low in 13 studies. Complete case (patients who did not complete the studies were not included in the analysis) results from 33 trials reporting on the incidence of diarrhea show a precise benefit from probiotics compared to active, placebo or no treatment control.After 5 days to 12 weeks of follow-up, the incidence of AAD in the probiotic group was 8% (259/3232) compared to 19% (598/3120) in the control group (RR 0.45, 95% CI 0.36 to 0.56; I² = 57%, 6352 participants; NNTB 9, 95% CI 7 to 13; moderate certainty evidence). Nineteen studies had loss to follow-up ranging from 1% to 46%. After making assumptions for those lost, the observed benefit was still statistically significant using an extreme plausible intention-to-treat (ITT) analysis, wherein the incidence of AAD in the probiotic group was 12% (436/3551) compared to 19% (664/3468) in the control group (7019 participants; RR 0.61; 95% CI 0.49 to 0.77; P <0.00001; I² = 70%). An a priori available case subgroup analysis exploring heterogeneity indicated that high dose (≥ 5 billion CFUs per day) is more effective than low probiotic dose (< 5 billion CFUs per day), interaction P value = 0.01. For the high dose studies the incidence of AAD in the probiotic group was 8% (162/2029) compared to 23% (462/2009) in the control group (4038 participants; RR 0.37; 95% CI 0.30 to 0.46; P = 0.06; moderate certainty evidence). For the low dose studies the incidence of AAD in the probiotic group was 8% (97/1155) compared to 13% (133/1059) in the control group (2214 participants; RR 0.68; 95% CI 0.46 to 1.01; P = 0.02). Again, assumptions for loss to follow-up using an extreme plausible ITT analysis was statistically significant. For high dose studies the incidence of AAD in the probiotic group was 13% (278/2218) compared to 23% (503/2207) in control group (4425 participants; RR 0.54; 95% CI 0.42 to 0.70; P <0.00001; I² = 68%; moderate certainty evidence).None of the 24 trials (4415 participants) that reported on adverse events reported any serious adverse events attributable to probiotics. Adverse event rates were low. After 5 days to 4 weeks follow-up, 4% (86/2229) of probiotics participants had an adverse event compared to 6% (121/2186) of control participants (RD 0.00; 95% CI -0.01 to 0.01; P < 0.00001; I² = 75%; low certainty evidence). Common adverse events included rash, nausea, gas, flatulence, abdominal bloating, and constipation.After 10 days to 12 weeks of follow-up, eight studies recorded data on our secondary outcome, the mean duration of diarrhea; with probiotics reducing diarrhea duration by almost one day (MD -0.91; 95% CI -1.38 to -0.44; P <0.00001; low certainty evidence). One study reported on microbiome characteristics, reporting no difference in changes with concurrent antibiotic and probiotic use. AUTHORS' CONCLUSIONS The overall evidence suggests a moderate protective effect of probiotics for preventing AAD (NNTB 9, 95% CI 7 to 13). Using five criteria to evaluate the credibility of the subgroup analysis on probiotic dose, the results indicate the subgroup effect based on high dose probiotics (≥ 5 billion CFUs per day) was credible. Based on high-dose probiotics, the NNTB to prevent one case of diarrhea is 6 (95% CI 5 to 9). The overall certainty of the evidence for the primary endpoint, incidence of AAD based on high dose probiotics was moderate due to the minor issues with risk of bias and inconsistency related to a diversity of probiotic agents used. Evidence also suggests that probiotics may moderately reduce the duration of diarrhea, a reduction by almost one day. The benefit of high dose probiotics (e.g. Lactobacillus rhamnosus orSaccharomyces boulardii) needs to be confirmed by a large well-designed multi-centered randomized trial. It is premature to draw firm conclusions about the efficacy and safety of 'other' probiotic agents as an adjunct to antibiotics in children. Adverse event rates were low and no serious adverse events were attributable to probiotics. Although no serious adverse events were observed among inpatient and outpatient children, including small studies conducted in the intensive care unit and in the neonatal unit, observational studies not included in this review have reported serious adverse events in severely debilitated or immuno-compromised children with underlying risk factors including central venous catheter use and disorders associated with bacterial/fungal translocation.
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Affiliation(s)
- Qin Guo
- West China Second University Hospital, West China Women's and Children's HospitalDepartment of PediatricsChengduChina
| | - Joshua Z Goldenberg
- National University of Natural MedicineHelfgott Research Institute2220 SW 1st AvePortlandORUSA97102
| | | | - Regina El Dib
- Institute of Science and Technology, UNESP ‐ Univ Estadual PaulistaDepartment of Biosciences and Oral DiagnosisSão José dos CamposSPBrazil
| | - Bradley C Johnston
- Dalhousie UniversityDepartment of Community Health and Epidemiology5790 University AvenueHalifaxNSCanadaB3H 1V7
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Abstract
In the past forty-five years, the field of probiotics has grown from a handful of laboratory studies and clinical ideas into a legitimate research and translational entity conferring multiple benefits to humans around the world. This has been founded upon three principles: (i) the need for alterna-tives to drugs that either have sub-optimal efficacy or severe adverse effects; (ii) a growing interest in natural products and microbes, in particular cata-lyzed by studies showing the extent of microbes within humans and on our planet; and (iii) evidence on the genetics and metabolic properties of probi-otic strains, and clinical studies showing their effectiveness. While some man-ufacturers have sadly taken advantage of the market growth to sell supple-ments and foods they term probiotic, without the necessary human study evidence, there are more and more companies basing their formulations on science. Adherence to the definition of what constitutes a probiotic, conclu-sions based on tested products not generalizations of the whole field, and applications emanating from microbiome research identifying new strains that provide benefits, will make the next forty-five years significantly changed approaches to health management. Exciting applications will emerge for car-diovascular, urogenital, respiratory, brain, digestive and skin health, detoxifi-cation, as well as usage across the world's ecosystems.
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Affiliation(s)
- Scarlett Puebla-Barragan
- Departments of Microbiology & Immunology, and Surgery, Western University.,Lawson Health Research Institute
| | - Gregor Reid
- Departments of Microbiology & Immunology, and Surgery, Western University.,Lawson Health Research Institute
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Chaves LD, McSkimming DI, Bryniarski MA, Honan AM, Abyad S, Thomas SA, Wells S, Buck M, Sun Y, Genco RJ, Quigg RJ, Yacoub R. Chronic kidney disease, uremic milieu, and its effects on gut bacterial microbiota dysbiosis. Am J Physiol Renal Physiol 2018; 315:F487-F502. [PMID: 29693447 PMCID: PMC6172581 DOI: 10.1152/ajprenal.00092.2018] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 04/19/2018] [Accepted: 04/19/2018] [Indexed: 12/12/2022] Open
Abstract
Several lines of evidence suggest that gut bacterial microbiota is altered in patients with chronic kidney disease (CKD), though the mechanism of which this dysbiosis takes place is not well understood. Recent studies delineated changes in gut microbiota in both CKD patients and experimental animal models using microarray chips. We present 16S ribosomal RNA gene sequencing of both stool pellets and small bowel contents of C57BL/6J mice that underwent a remnant kidney model and establish that changes in microbiota take place in the early gastrointestinal tract. Increased intestinal urea concentration has been hypothesized as a leading contributor to dysbiotic changes in CKD. We show that urea transporters (UT)-A and UT-B mRNA are both expressed throughout the whole gastrointestinal tract. The noted increase in intestinal urea concentration appears to be independent of UTs' expression. Urea supplementation in drinking water resulted in alteration in bacterial gut microbiota that is quite different than that seen in CKD. This indicates that increased intestinal urea concentration might not fully explain the CKD- associated dysbiosis.
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Affiliation(s)
- Lee D Chaves
- Department of Internal Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, New York
| | - Daniel I McSkimming
- Genome, Environment, and Microbiome Community of Excellence, University at Buffalo , Buffalo, New York
| | - Mark A Bryniarski
- Department of Pharmaceutical Sciences, University at Buffalo School of Pharmacy and Pharmaceutical Sciences , Buffalo, New York
| | - Amanda M Honan
- Department of Internal Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, New York
| | - Sham Abyad
- Department of Internal Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, New York
| | - Shruthi A Thomas
- Department of Internal Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, New York
| | - Steven Wells
- Department of Internal Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, New York
| | - Michael Buck
- Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, New York
| | - Yijun Sun
- Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, New York
| | - Robert J Genco
- Department of Oral Biology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, New York
| | - Richard J Quigg
- Department of Internal Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, New York
| | - Rabi Yacoub
- Department of Internal Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, New York
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11
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Agamennone V, Krul CAM, Rijkers G, Kort R. A practical guide for probiotics applied to the case of antibiotic-associated diarrhea in The Netherlands. BMC Gastroenterol 2018; 18:103. [PMID: 30078376 PMCID: PMC6091175 DOI: 10.1186/s12876-018-0831-x] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Accepted: 06/21/2018] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Antibiotic-associated diarrhea (AAD) is a side-effect frequently associated with the use of broad spectrum antibiotics. Although a number of clinical studies show that co-administration of specific probiotics reduces the risk for AAD, there is still unclarity among healthcare professionals on the recommendation of probiotic products. This paper aims at a practical guide to inform healthcare professionals, patients and consumers about the exact product characteristics of available probiotics with a proven efficacy to prevent AAD. METHODS The workflow in this paper includes three consecutive steps: 1) systematic review of relevant clinical studies for effective probiotics by a meta-analysis, 2) compilation of a list of available probiotic products, and 3) recommendation of probiotic products that match effective formulations. Our systematic review on the efficacy of probiotics for the prevention of AAD included only studies with randomized, double blind placebo-controlled trials, a clear definition of antibiotic associated diarrhea, and a probiotic administration regime for at least the duration of the antibiotic therapy. RESULTS Using our inclusion criteria, we selected 32 out of 128 identified trials and pooled the results of these studies for each specific dairy product and food supplement. The results indicate a total of seven single or multiple-strain formulations favoring the probiotic treatment group, with the strain Lactobacillus rhamnosus GG being the most effective [relative risk ratio of probiotic versus placebo 0.30 (95% CI 0.16-0.5)]. We selected products for recommendation from a compiled list of all probiotic dairy products and food supplements available in The Netherlands and categorized them into groups of products showing effects against the incidence of AAD in at least one, two or three independent clinical studies. We excluded all products which did not unambiguously declare on the label the specific probiotic strain(s) and the number of colony forming units. CONCLUSION Here we present a practical guide that informs healthcare professionals and patients on the availability of probiotic products with a proven efficacy for the prevention of AAD.
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Affiliation(s)
- Valeria Agamennone
- Microbiology and Systems Biology, Netherlands Organization for Applied Scientific Research (TNO), Utrechtseweg 48, 3704 HE Zeist, The Netherlands
| | - Cyrille A. M. Krul
- Microbiology and Systems Biology, Netherlands Organization for Applied Scientific Research (TNO), Utrechtseweg 48, 3704 HE Zeist, The Netherlands
| | - Ger Rijkers
- University College Roosevelt, Lange Noordstraat 1, 4331 CB Middelburg, The Netherlands
| | - Remco Kort
- Microbiology and Systems Biology, Netherlands Organization for Applied Scientific Research (TNO), Utrechtseweg 48, 3704 HE Zeist, The Netherlands
- Artis-Micropia, Plantage Kerklaan 38, 1018 CZ Amsterdam, The Netherlands
- Department of Molecular Cell Biology, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
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Shi Y, Zhao X, Zhao J, Zhang H, Zhai Q, Narbad A, Chen W. A mixture of Lactobacillus species isolated from traditional fermented foods promote recovery from antibiotic-induced intestinal disruption in mice. J Appl Microbiol 2018; 124:842-854. [PMID: 29314490 DOI: 10.1111/jam.13687] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Revised: 11/30/2017] [Accepted: 12/12/2017] [Indexed: 12/18/2022]
Abstract
AIMS This study evaluated the antibiotic-induced changes in microbial ecology, intestinal dysbiosis and low-grade inflammation; and the combined effect of four different Lactobacillus species on recovery of microbiota composition and improvement of gut barrier function in mice. METHODS AND RESULTS Administration of the antibiotic ampicillin for 2 weeks decreased microbial community diversity, induced caecum tumefaction and increased gut permeability in mice. Application of a probiotic cocktail of four Lactobacillus species (JUP-Y4) modulated the microbiota community structure and promoted the abundance of potentially beneficial bacteria such as Akkermansia. Ampicillin administration led to a decline in Bacteroidetes from 46·6 ± 3·91% to 0·264 ± 0·0362%; the addition of JUP-Y4 restored this to 41·4 ± 2·87%. This probiotic supplementation was more effective than natural restoration, where the levels of Bacteroidetes were only restored to 29·3 ± 2·07%. Interestingly, JUP-Y4 treatment was more effective in the restoration of microbiota in faecal samples than in caecal samples. JUP-Y4 also significantly reduced the levels of d-lactate and endotoxin (lipopolysaccharide, LPS) in the serum of mice, and increased the expression of tight-junction proteins while reducing the production of inflammatory cytokines (TNF-α, IL-6, MCP-1, IFN-γ and IL-1β) in the ileum and the colon of antibiotic-treated mice. CONCLUSIONS JUP-Y4 not only promoted recovery from antibiotic-induced gut dysbiosis, but also enhanced the function of the gut barrier, reduced inflammation and lowered levels of circulating endotoxin in mice. SIGNIFICANCE AND IMPACT OF THE STUDY Consumption of a mixture of Lactobacillus species may encourage faster recovery from antibiotic-induced gut dysbiosis and gut microbiota-related immune disturbance.
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Affiliation(s)
- Y Shi
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.,School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.,International Joint Research Laboratory for Probiotics at Jiangnan University, Wuxi, Jiangsu, China
| | - X Zhao
- School of Life Science and Technology, Shanghai Tech University, Shanghai, China
| | - J Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.,School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| | - H Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.,School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.,National Engineering Research Centre for Functional Food, Wuxi, Jiangsu, China
| | - Q Zhai
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.,School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.,International Joint Research Laboratory for Probiotics at Jiangnan University, Wuxi, Jiangsu, China.,National Engineering Research Centre for Functional Food, Wuxi, Jiangsu, China
| | - A Narbad
- UK-China Joint Centre on Probiotic Bacteria, Norwich, UK.,Gut Health and Food Safety Programme, Quadram Institute Bioscience, Norwich, UK
| | - W Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.,School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.,National Engineering Research Centre for Functional Food, Wuxi, Jiangsu, China.,Beijing Innovation Centre of Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing, China
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13
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Ali A. Lyme Disease. Integr Med (Encinitas) 2018. [DOI: 10.1016/b978-0-323-35868-2.00023-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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14
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Gong J, Bai T, Zhang L, Qian W, Song J, Hou X. Inhibition effect of Bifidobacterium longum, Lactobacillus acidophilus, Streptococcus thermophilus and Enterococcus faecalis and their related products on human colonic smooth muscle in vitro. PLoS One 2017; 12:e0189257. [PMID: 29216305 PMCID: PMC5720742 DOI: 10.1371/journal.pone.0189257] [Citation(s) in RCA: 8] [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: 03/11/2017] [Accepted: 11/22/2017] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE To investigate the effects of four strains, generally used in clinic, including Bifidobacterium longum, Lactobacillus acidophilus, Streptococcus thermophilus and Enterococcus faecalis, and their related products on human colonic smooth muscle in vitro. METHODS Human colonic circular muscle strips obtained from disease-free margins of resected segments from 25 patients with colorectal cancer were isometrically examined in a constant-temperature organ bath and exposed to different concentrations of living bacteria, sonicated cell fractions and cell-free supernatant (CFS). The area under the curve (AUC) representing the contractility of smooth muscle strips was calculated. RESULTS (1) The four living probiotics inhibited the contractility of human colonic muscle strips only at high concentration (1010 CFUs/mL, all P<0.05). (2) The sonicated cell fractions from the four probiotics obviously inhibited human colonic smooth muscle strips in a dose-dependent manner (P<0.01). (3) The CFS from the four probiotics also inhibited colonic smooth muscle strips in a dose-dependent manner (all P<0.05). (4) The inhibition effect of CFS from Streptococcus thermophilus and Enterococcus faecalis decreased obviously when pretreated with NG-nitro-L-arginine (L-NNA, 10-5 mol/L) (P<0.05), but not the Bifidobacterium longum and Lactobacillus acidophilus (P>0.05). CONCLUSION Four common probiotics related products, including the sonicated cell fractions and the CFS, obviously inhibited human colonic smooth muscles strips contraction in a dose-dependent manner. Only high concentration living probiotics (1010 CFUs/mL) can inhibit the colonic smooth muscles strips contraction. The NO pathway may be partly involved in the inhibitory effect of CFS from Streptococcus thermophilus and Enterococcus faecalis.
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Affiliation(s)
- Jing Gong
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Bai
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lei Zhang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Qian
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jun Song
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Draper K, Ley C, Parsonnet J. Probiotic guidelines and physician practice: a cross-sectional survey and overview of the literature. Benef Microbes 2017; 8:507-519. [DOI: 10.3920/bm2016.0146] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Probiotic use by patients and physicians has dramatically increased over the last decade, although definitive evidence is often lacking for their use. We examined probiotic-prescribing practices among health care providers (HCP) at a tertiary medical centre and compared these practices to clinical guidelines. HCP at the Stanford Medical Center received a survey on probiotic prescribing practices including choice of probiotic and primary indications. A broad overview of the literature was performed. Among 2,331 HCP surveyed, 632 responded. Of the 582 of these who routinely prescribed medications, 61% had recommended probiotic foods or supplements to their patients. Women and gastroenterologists were more likely to prescribe probiotics (odds ratio (OR): 1.5, 95% confidence interval (CI): 1.0-2.1; OR: 3.9, 95% CI: 1.5-10.1, respectively). Among probiotic prescribers, 50% prescribed inconsistently or upon patient request, and 40% left probiotic choice to the patient. Common indications for probiotics, particularly Lactobacillus GG, were prevention and treatment of antibiotic-associated diarrhoea (79 and 66%, respectively). Probiotics were often prescribed for ‘general bowel health’ or at patient request (27 and 39% of responders, respectively). Most respondents (63%) thought an electronic medical record (EMR) pop-up would change probiotic prescribing patterns. However, a review of published guidelines and large trials found inconsistencies in probiotic indications, dosages and strain selection. Probiotic prescribing is common but lacks consistency, with choice of probiotic frequently left to the patient, even for indications with some strain-specific evidence. Implementation of EMR pop-ups/pocket guides may increase consistency in probiotic prescribing, although the lack of clear and consistent guidelines must first be addressed with large, well-designed clinical trials.
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Affiliation(s)
- K. Draper
- Division of Gastroenterology and Hepatology, Stanford School of Medicine, 300 Pasteur Drive, MC 5187, Stanford, CA 94305-5119, USA
| | - C. Ley
- Division of Infectious Diseases and Geographic Medicine, Stanford School of Medicine, 300 Pasteur Drive, MC 5187, Stanford, CA 94305-5119, USA
| | - J. Parsonnet
- Division of Infectious Diseases and Geographic Medicine, Stanford School of Medicine, 300 Pasteur Drive, MC 5187, Stanford, CA 94305-5119, USA
- Health Research and Policy, Department of Medicine, Stanford School of Medicine, 150 Governor’s Lane, HRP Redwood Building, Stanford, CA 94305-5405, USA
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Draper K, Ley C, Parsonnet J. A survey of probiotic use practices among patients at a tertiary medical centre. Benef Microbes 2017; 8:345-351. [PMID: 28403649 DOI: 10.3920/bm2016.0148] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Probiotic use has skyrocketed in recent years. Little is known, however, about patient knowledge and practices regarding probiotic use, especially in the context of antibiotic use. An invitation to complete a short, anonymous, electronic survey was sent by email to 965 patients at a tertiary medical centre in California who had agreed to be contacted for participation in research studies. Questions were asked about both probiotic and antibiotic use in the prior three months. Of 333 survey respondents, 55% had recently used probiotics, including food products and/or supplements (90 and 60% of probiotic users, respectively). Women were more likely than men to have used probiotics (odds ratio (OR): 1.99; 95% confidence interval (CI): 1.2-3.4). Health care providers (HCP) had prescribed antibiotics to 79 (24%) respondents in the preceding three months. Among antibiotic users, 33% had initiated or changed probiotics at the time of antibiotic use, usually without a recommendation from their prescribing HCP (72%). Only 12% of those who took probiotics with antibiotics had received a specific recommendation from their HCP. Most patients chose to take probiotic mixtures (56%), with few selecting evidence-based strains, such as Lactobacillus rhamnosus GG (11%). Regular probiotic use among patients is common. Typically, these probiotics are not recommended by a HCP, even in conjunction with antibiotic prescriptions. While a growing body of evidence supports specific probiotic strains for the prevention of antibiotic-associated diarrhoea, patients are often not receiving a specific recommendation from their HCP and appear to be taking strains without guidance from supporting evidence.
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Affiliation(s)
- K Draper
- 1 Division of Gastroenterology and Hepatology, Stanford School of Medicine, 300 Pasteur Drive, MC 5187, Stanford, CA 94305-5119, USA
| | - C Ley
- 2 Division of Infectious Diseases and Geographic Medicine, Stanford School of Medicine, 300 Pasteur Drive, MC 5187, Stanford, CA 94305-5119, USA
| | - J Parsonnet
- 2 Division of Infectious Diseases and Geographic Medicine, Stanford School of Medicine, 300 Pasteur Drive, MC 5187, Stanford, CA 94305-5119, USA.,3 Health Research and Policy, Department of Medicine, Stanford School of Medicine, 150 Governor's Lane, HRP Redwood Building, Stanford, CA 94305-5405, USA
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Abstract
Although Whipple's disease (WD) has been treated with antibiotics since the early 50s, the best antibiotics and the duration of the therapy have not yet been established. We consider here the pro and cons of the two most commonly used therapies, ceftriaxone followed by trimethoprim-sulfamethoxazole (TMP-SMZ) and hydroxychloroquine in combination with doxycycline. The therapy based on ceftriaxone and TMP-SMZ is efficient in the vast majority of patients for the first few years. However, since reinfections or reactivations can occur, a life-long prophylaxis is necessary and doxycycline is nowadays the best option. We thus propose a therapy based on merging these to therapies together, ceftriaxone, and TMP-SMZ for the first year(s) and then life-long prophylaxis with doxycycline.
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Affiliation(s)
- Federico Biagi
- a First Department of Internal Medicine , Fondazione IRCCS Policlinico San Matteo, University of Pavia , Pavia , Italy
| | - Gian Luigi Biagi
- b Department of Pharmacology , University of Bologna , Bologna , Italy
| | - Gino Roberto Corazza
- a First Department of Internal Medicine , Fondazione IRCCS Policlinico San Matteo, University of Pavia , Pavia , Italy
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18
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Celiberto LS, Bedani R, Rossi EA, Cavallini DCU. Probiotics: The scientific evidence in the context of inflammatory bowel disease. Crit Rev Food Sci Nutr 2017; 57:1759-1768. [PMID: 25996176 DOI: 10.1080/10408398.2014.941457] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Inflammatory bowel disease (IBD) generally comprises Crohn's disease (CD) and ulcerative colitis (UC), and their main characteristic is the intestinal mucosa inflammation. Although its origin is not yet fully known, there is growing evidence related to genetics, intestinal microbiota composition, and the immune system factors such as precursors for the initiation and progression of intestinal conditions. The use of certain probiotic microorganisms has been touted as a possible and promising therapeutic approach in reducing the risk of inflammatory bowel disease, specifically ulcerative colitis. Several mechanisms have been proposed to explain the benefits of probiotics, indicating that some bacterial strains are able to positively modulate the intestinal microbiota and the immune system, and to produce metabolites with anti-inflammatory properties. The aim of this paper is to bring together the various results and information, based on scientific evidence, that are related to probiotics and inflammatory bowel disease, emphasizing the possible mechanisms involved in this action.
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Affiliation(s)
- Larissa Sbaglia Celiberto
- a Department of Food & Nutrition , Faculty of Pharmaceutical Sciences, São Paulo State University (UNESP) , Araraquara , SP , Brazil
| | - Raquel Bedani
- b Departament of Biochemical and Pharmaceutical Technology , Faculty of Pharmaceutical Sciences, University of São Paulo (USP) Properties , SP , Brazil
| | - Elizeu Antonio Rossi
- a Department of Food & Nutrition , Faculty of Pharmaceutical Sciences, São Paulo State University (UNESP) , Araraquara , SP , Brazil
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Effectiveness of Lactobacillus helveticus and Lactobacillus rhamnosus for the management of antibiotic-associated diarrhoea in healthy adults: a randomised, double-blind, placebo-controlled trial. Br J Nutr 2016; 116:94-103. [PMID: 27169634 DOI: 10.1017/s0007114516001665] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Broad-spectrum antibiotic use can disrupt the gastrointestinal microbiota resulting in diarrhoea. Probiotics may be beneficial in managing this type of diarrhoea. The aim of this 10-week randomised, double-blind, placebo-controlled, parallel study was to investigate the effect of Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011 supplementation on antibiotic-associated diarrhoea in healthy adults. Subjects were randomised to receive 1 week of amoxicillin-clavulanic acid (875 mg/125 mg) once per day, plus a daily dose of 8×109 colony-forming units of a multi-strain probiotic (n 80) or placebo (n 80). The probiotic or placebo intervention was maintained for 1 week after completion of the antibiotic. Primary study outcomes of consistency and frequency of bowel movements were not significantly different between the probiotic and placebo groups. The secondary outcomes of diarrhoea-like defecations, Gastrointestinal Symptoms Rating Scale scores, safety parameters and adverse events were not significantly different between the probiotic intervention and the placebo. A post hoc analysis on the duration of diarrhoea-like defecations showed that probiotic intervention reduced the length of these events by 1 full day (probiotic, 2·70 (sem 0·36) d; placebo, 3·71 (sem 0·36) d; P=0·037; effect size=0·52). In conclusion, this study provides novel evidence that L. helveticus R0052 and L. rhamnosus R0011 supplementation significantly reduced the duration of diarrhoea-like defecations in healthy adults receiving antibiotics.
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McFarland LV, Ozen M, Dinleyici EC, Goh S. Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections. World J Gastroenterol 2016; 22:3078-3104. [PMID: 27003987 PMCID: PMC4789985 DOI: 10.3748/wjg.v22.i11.3078] [Citation(s) in RCA: 106] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Revised: 01/12/2016] [Accepted: 02/22/2016] [Indexed: 02/06/2023] Open
Abstract
Antibiotic-associated diarrhea (AAD) and Clostridum difficile infections (CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases PubMed (June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications (required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar (discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics.
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Goldenberg JZ, Lytvyn L, Steurich J, Parkin P, Mahant S, Johnston BC. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev 2015:CD004827. [PMID: 26695080 DOI: 10.1002/14651858.cd004827.pub4] [Citation(s) in RCA: 85] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Antibiotics are frequently prescribed in children. They alter the microbial balance within the gastrointestinal tract, commonly resulting in antibiotic-associated diarrhea (AAD). Probiotics may prevent AAD via restoration of the gut microflora. OBJECTIVES The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children. SEARCH METHODS MEDLINE, EMBASE, CENTRAL, CINAHL, AMED, and the Web of Science (inception to November 2014) were searched along with specialized registers including the Cochrane IBD/FBD review group, CISCOM (Centralized Information Service for Complementary Medicine), NHS Evidence, the International Bibliographic Information on Dietary Supplements as well as trial registries. Letters were sent to authors of included trials, nutraceutical and pharmaceutical companies, and experts in the field requesting additional information on ongoing or unpublished trials. Conference proceedings, dissertation abstracts, and reference lists from included and relevant articles were also searched. SELECTION CRITERIA Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the incidence of diarrhea secondary to antibiotic use were considered for inclusion. DATA COLLECTION AND ANALYSIS Study selection, data extraction as well as methodological quality assessment using the risk of bias instrument was conducted independently and in duplicate by two authors. Dichotomous data (incidence of diarrhea, adverse events) were combined using a pooled risk ratio (RR) or risk difference (RD), and continuous data (mean duration of diarrhea, mean daily stool frequency) as mean difference (MD), along with their corresponding 95% confidence interval (95% CI). For overall pooled results on the incidence of diarrhea, sensitivity analyses included available case versus extreme-plausible analyses and random- versus fixed-effect models. To explore possible explanations for heterogeneity, a priori subgroup analysis were conducted on probiotic strain, dose, definition of antibiotic-associated diarrhea, as well as risk of bias. We also conducted post hoc subgroup analyses by patient diagnosis, single versus multi-strain, industry sponsorship, and inpatient status. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. MAIN RESULTS Twenty-three studies (3938 participants) met the inclusion criteria. Trials included treatment with either Bacillus spp., Bifidobacterium spp., Clostridium butyricum, Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., orStreptococcus spp., alone or in combination. Eleven studies used a single strain probiotic, four combined two probiotic strains, three combined three probiotic strains, one combined four probiotic strains, two combined seven probiotic strains, one included ten probiotic strains, and one study included two probiotic arms that used three and two strains respectively. The risk of bias was determined to be high or unclear in 13 studies and low in 10 studies. Available case (patients who did not complete the studies were not included in the analysis) results from 22/23 trials reporting on the incidence of diarrhea show a precise benefit from probiotics compared to active, placebo or no treatment control. The incidence of AAD in the probiotic group was 8% (163/1992) compared to 19% (364/1906) in the control group (RR 0.46, 95% CI 0.35 to 0.61; I(2) = 55%, 3898 participants). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate. This benefit remained statistically significant in an extreme plausible (60% of children loss to follow-up in probiotic group and 20% loss to follow-up in the control group had diarrhea) sensitivity analysis, where the incidence of AAD in the probiotic group was 14% (330/2294) compared to 19% (426/2235) in the control group (RR 0.69; 95% CI 0.54 to 0.89; I(2) = 63%, 4529 participants). None of the 16 trials (n = 2455) that reported on adverse events documented any serious adverse events attributable to probiotics. Meta-analysis excluded all but an extremely small non-significant difference in adverse events between treatment and control (RD 0.00; 95% CI -0.01 to 0.01). The majority of adverse events were in placebo, standard care or no treatment group. Adverse events reported in the studies include rash, nausea, gas, flatulence, abdominal bloating, abdominal pain, vomiting, increased phlegm, chest pain, constipation, taste disturbance, and low appetite. AUTHORS' CONCLUSIONS Moderate quality evidence suggests a protective effect of probiotics in preventing AAD. Our pooled estimate suggests a precise (RR 0.46; 95% CI 0.35 to 0.61) probiotic effect with a NNT of 10. Among the various probiotics evaluated, Lactobacillus rhamnosus or Saccharomyces boulardii at 5 to 40 billion colony forming units/day may be appropriate given the modest NNT and the likelihood that adverse events are very rare. It is premature to draw conclusions about the efficacy and safety of other probiotic agents for pediatric AAD. Although no serious adverse events were observed among otherwise healthy children, serious adverse events have been observed in severely debilitated or immuno-compromised children with underlying risk factors including central venous catheter use and disorders associated with bacterial/fungal translocation. Until further research has been conducted, probiotic use should be avoided in pediatric populations at risk for adverse events. Future trials would benefit from a standard and valid outcomes to measure AAD.
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Scientific evidence for health effects attributed to the consumption of probiotics and prebiotics: an update for current perspectives and future challenges. Br J Nutr 2015; 114:1993-2015. [PMID: 26443321 DOI: 10.1017/s0007114515003864] [Citation(s) in RCA: 120] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Probiotics and prebiotics, mainly commercialised as food ingredients and also as supplements, are considered highly profitable niche markets. However, in recent years, the food industry has suffered from a series of health claim restrictions on probiotics and prebiotics in many parts of the world, including those made by the European Food Safety Authority. Therefore, we reviewed the core benefits of probiotic and prebiotic consumption on health. A number of studies have examined the prevention and/or management of intestinal infections, respiratory tract infections, CVD, osteoporosis, urogenital infections, cavities, periodontal disease and halitosis, allergic reactions, inflammatory bowel disease and irritable bowel syndrome and Helicobacter pylori gastric infections. In fact, a deeper understanding of the mechanisms involved in human microbiota and immune system modulation by probiotics and prebiotics relies on continuous efforts to establish suitable biomarkers of health and diseases risk factors for the design of clinical trials required for health claim approval. In spite of the promising results, the performance of large, long-term, well-planned, well-aligned clinical studies is crucial to provide more reliability and a more solid basis for the outcomes achieved and to support the potential use of probiotics and prebiotics in clinical practice.
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Kvasnovsky CL, Bjarnason I, Papagrigoriadis S. What colorectal surgeons should know about probiotics: a review. Colorectal Dis 2015; 17:840-8. [PMID: 26359925 DOI: 10.1111/codi.13046] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Accepted: 06/23/2015] [Indexed: 02/08/2023]
Affiliation(s)
- C L Kvasnovsky
- Department of Colorectal Surgery, King's College Hospital, London, UK.,Department of Surgery, University of Maryland Medical Center, Baltimore, Maryland, USA
| | - I Bjarnason
- Department of Colorectal Surgery, King's College Hospital, London, UK
| | - S Papagrigoriadis
- Department of Colorectal Surgery, King's College Hospital, London, UK
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Enteral ecoimmunonutrition reduced enteral permeability and serum ghrelin activity in severe cerebral stroke patients with lung infection. Cell Biochem Biophys 2015; 71:195-8. [PMID: 25142270 DOI: 10.1007/s12013-014-0184-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The study analyzed how enteral ecoimmunonutrition, which comprises probiotics, glutamine, fish oil, and Enteral Nutritional Suspension (TPF), can impact on the enteral permeability and serum Ghrelin activity in severe cerebral stroke patients with lung infection. Among 190 severe cerebral stroke patients with tolerance to TPF, they were randomized into control and treatment groups after antibiotics treatment due to lung infections. There were 92 patients in the control group and 98 patients in treatment group. The control group was treated with TPF and the treatment group was treated with enteral ecoimmunonutrition, which comprises probiotics, glutamine, fish oil, and Enteral Nutritional Suspension. All patients received continuous treatments through nasoenteral or nasogastric tubes. 7, 14, and 21 days after the treatments, the enteral tolerance to nutrition was observed in both groups. The tests included abdominal pain, bloating, diarrhea, and lactulose/mannitol (L/M) ratio. Serum Ghrelin levels were determined by ELISA. The incidence of abdominal pain, bloating, diarrhea was lower in the treatment group and enteral tolerance to nutrition was also superior to the control group. No difference in serum Ghrelin level was observed between the control and treatment groups with enteral intolerance to nutrition. However, in patients with enteral tolerance to nutrition, the treatment group showed lower enteral nutrition and lower enteral permeability compared to the control group. In severe cerebral stroke patients with lung infection, enteral ecoimmunonutrition after antibiotics treatment improved enteral tolerance to nutrition and reduced enteral permeability; meanwhile, it lowered the serum Ghrelin activity, which implied the high serum Ghrelin reduces enteral permeability.
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Janiaud P, Lajoinie A, Cour-Andlauer F, Cornu C, Cochat P, Cucherat M, Gueyffier F, Kassai B. Different treatment benefits were estimated by clinical trials performed in adults compared with those performed in children. J Clin Epidemiol 2015; 68:1221-31. [PMID: 26164751 DOI: 10.1016/j.jclinepi.2015.06.021] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2013] [Revised: 12/20/2014] [Accepted: 06/29/2015] [Indexed: 01/01/2023]
Abstract
OBJECTIVE Our main objective was to see whether the therapeutic benefit observed in placebo controlled randomized controlled trials (RCTs) is different between adults and children. STUDY DESIGN AND SETTING We searched three electronic databases for meta-analyses that included double-blind, placebo-controlled RCTs with separate results for adults and children. The selected reviews were classified according to disease and drug used. The heterogeneity of treatment response between adults and children was measured using ratio of odds ratios (RORs). RESULTS We selected 89 meta-analyses and calculated RORs for 124 drugs. Heterogeneity in the direction of the treatment effect was observed in one drug and heterogeneity in the quantity of the treatment effect for 13 drugs, indicating significantly different treatment effect in adults when compared with children. RORs were not significantly different from 1 for 110 drugs. For 36 of these drugs, the treatment effect was confirmed in both populations. CONCLUSION We found different treatment benefits estimated by clinical trials performed in adults compared with those performed in children for 14 of 124 drugs. Data on dose adjustment and child age groups from RCTs were not adequately reported to investigate their influence on the treatment benefit dissimilarities.
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Affiliation(s)
| | - Audrey Lajoinie
- Clinical Investigation Center, EPICIME, INSERM CIC 1407/UMR 5558 CNRS, Bron, France
| | - Fleur Cour-Andlauer
- Clinical Investigation Center, EPICIME, INSERM CIC 1407/UMR 5558 CNRS, Bron, France
| | - Catherine Cornu
- UMR 5558 CRNS Lyon, University of Lyon 1, France; Clinical Investigation Center, EPICIME, INSERM CIC 1407/UMR 5558 CNRS, Bron, France; Department of Clinical Pharmacology, Hospices Civils de Lyon, Lyon, France
| | - Pierre Cochat
- UMR 5558 CRNS Lyon, University of Lyon 1, France; Department of Pediatric Nephrology, Hopital Femme Mere Enfant, Lyon, France
| | - Michel Cucherat
- Department of Clinical Pharmacology, Hospices Civils de Lyon, Lyon, France
| | - François Gueyffier
- UMR 5558 CRNS Lyon, University of Lyon 1, France; Clinical Investigation Center, EPICIME, INSERM CIC 1407/UMR 5558 CNRS, Bron, France
| | - Behrouz Kassai
- UMR 5558 CRNS Lyon, University of Lyon 1, France; Clinical Investigation Center, EPICIME, INSERM CIC 1407/UMR 5558 CNRS, Bron, France; Department of Clinical Pharmacology, Hospices Civils de Lyon, Lyon, France.
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Pei R, Martin DA, DiMarco DM, Bolling BW. Evidence for the effects of yogurt on gut health and obesity. Crit Rev Food Sci Nutr 2015; 57:1569-1583. [DOI: 10.1080/10408398.2014.883356] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Dietrich CG, Kottmann T, Alavi M. Commercially available probiotic drinks containing Lactobacillus casei DN-114001 reduce antibiotic-associated diarrhea. World J Gastroenterol 2014; 20:15837-15844. [PMID: 25400470 PMCID: PMC4229551 DOI: 10.3748/wjg.v20.i42.15837] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Revised: 05/26/2014] [Accepted: 06/26/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of Lactobacillus-containing commercially available probiotic formulations in Germany during antibiotic treatment with an analysis of cost-efficiency.
METHODS: In an observational study, we analyzed the frequency of bowel movements from 258 patients with infections in a primary care hospital in western Germany; 107 of the patients were offered a probiotic drink containing at least 10 billion cultures of Lactobacillus casei DN 114001 b.i.d. The economic analysis was based on the costs of patient isolation vs preventive intake of probiotics. In a second pilot study, two commercially available probiotic drinks with different Lactobacillus casei strains were directly compared in 60 patients in a randomized controlled fashion.
RESULTS: In the first study, the incidence of antibiotic-associated diarrhea (AAD) was significantly reduced in the intervention group (6.5% vs 28.4%), and the duration of AAD in days was significantly shorter (1.7 ± 1.1 vs 3.1 ± 2.1). Higher age and creatinine and lower albumin were identified as risk factors for AAD. Ampicillin was the antibiotic with the highest rate of AAD (50%) and with the greatest AAD reduction in the probiotic group (4.2%, relative risk reduction 92%). The economic analysis showed a cost advantage of nearly 60000 €/year in a department of this size. The second study confirmed the preventive effect of the drink with Lactobacillus casei DN114001; however, there were no advantages found for the other tested probiotic drink containing Lactobacillus casei Shirota.
CONCLUSION: In contrast to a drink containing Lactobacillus casei Shirota, a commercially available probiotic drink containing Lactobacillus casei DN 114001 cost-efficiently reduces the prevalence of AAD during antibiotic treatment.
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Beirão EM, Padovan ACB, Furtado JJD, Colombo AL, Medeiros EAS. Does the change on gastrointestinal tract microbiome affects host? Braz J Infect Dis 2014; 18:660-3. [PMID: 24835619 PMCID: PMC9425252 DOI: 10.1016/j.bjid.2014.04.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2014] [Revised: 03/28/2014] [Accepted: 04/21/2014] [Indexed: 01/04/2023] Open
Abstract
During the past decade, studies on the composition of human microbiota and its relation to the host became one of the most explored subjects of the medical literature. The development of high-throughput molecular technologies allowed a deeper characterization of human microbiota and a better understanding of its relationship with health and disease. Changes in human habits including wide use of antimicrobials can result in dysregulation of host–microbiome homeostasis, with multiple consequences. The purpose of this review is to highlight the most important evidence in the literature of host–microbiome interactions and illustrate how these intriguing relations may lead to new treatment and prevention strategies.
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Affiliation(s)
- Elisa M Beirão
- Department of Infectiology, Hospital Heliópolis, São Paulo, SP, Brazil.
| | - Ana Carolina B Padovan
- Micology Special Laboratory, Disciplina de Infectologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | | | - Arnaldo L Colombo
- Micology Special Laboratory, Disciplina de Infectologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | - Eduardo A S Medeiros
- Service of Hospital Infection Control, Disciplina de Infectologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil
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McFarland LV, Goh S. Preventing pediatric antibiotic-associated diarrhea and Clostridium difficile infections with probiotics: A meta-analysis. World J Meta-Anal 2013; 1:102-120. [DOI: 10.13105/wjma.v1.i3.102] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2013] [Revised: 10/01/2013] [Accepted: 10/20/2013] [Indexed: 02/05/2023] Open
Abstract
AIM: To assess the efficacy and safety of probiotics for preventing pediatric: (1) antibiotic associated diarrhea and (2) Clostridium difficile (C. difficile) infections.
METHODS: On June 3, 2013, we searched PubMed (1960-2013), EMBASE (1974-2013), Cochrane Database of Systematic Reviews (1990-2013), CINAHL (1981-2013), AMED (1985-2013), and ISI Web of Science (2000-2013). Additionally, we conducted an extensive grey literature search including contact with National Institutes of Health Clinical Trials Registry, abstracts from annual infectious disease and gastroenterology meetings, experts in the field and correspondence with authors. The primary outcomes were the incidence of antibiotic-associated diarrhea (AAD) and C. difficile infections (CDI). Dichotomous outcomes (e.g., incidence of AAD or CDI) were pooled using a random-effects model to calculate the relative risk and corresponding 95% confidence interval (95%CI) and weighted on study quality. To explore possible explanations for heterogeneity, a priori subgroup analysis were conducted on probiotic strain type, daily dose, quality of study and safety of probiotics. The overall quality of the evidence supporting each outcome was assessed using the grading of recommendations, assessment, development and evaluation criteria.
RESULTS: A total of 1329 studies were identified with 22 trials (23 treatment arms and 4155 participants) meeting eligibility requirements for our review of prevention of AAD and 5 trials (1211 participants) for the prevention of CDI. Trials in adult populations, trials of uncertain antibiotic exposure or studies which did not provide incidence of AAD were excluded. We found 12 trials testing a single strain of probiotic and 10 trials testing a mixture of probiotic strains. Probiotics (all strains combined) significantly reduced the incidence of pediatric AAD (pooled RR = 0.42, 95%CI: 0.33-0.53) and significantly reduced pediatric CDI (pooled RR = 0.35, 95%CI: 0.13-0.92). Of the two strains with multiple trials, both significantly reduced pediatric AAD: Saccharomyces boulardii lyo (pooled RR = 0.43, 95%CI: 0.32-0.60) and Lactobacillus rhamnosus GG (pooled RR = 0.36, 95%CI: 0.19-0.69). There was no significant effect by type of antibiotic, or by duration or dose of probiotic. No adverse events associated were found in the 22 controlled trials relating to the use of probiotics.
CONCLUSION: This meta-analysis found that probiotics significantly prevented pediatric antibiotic associated diarrhea and pediatric CDI, but the efficacy varies significantly by the strain of the probiotic.
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Strategies to minimize antibiotic resistance. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2013; 10:4274-305. [PMID: 24036486 PMCID: PMC3799537 DOI: 10.3390/ijerph10094274] [Citation(s) in RCA: 245] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2013] [Revised: 09/02/2013] [Accepted: 09/03/2013] [Indexed: 02/07/2023]
Abstract
Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs) and various data such as pharmacokinetic (PK) and pharmacodynamic (PD) properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST), clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care), the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students) regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing). The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics.
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Mego M, Holec V, Drgona L, Hainova K, Ciernikova S, Zajac V. Probiotic bacteria in cancer patients undergoing chemotherapy and radiation therapy. Complement Ther Med 2013; 21:712-23. [PMID: 24280481 DOI: 10.1016/j.ctim.2013.08.018] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2013] [Revised: 08/01/2013] [Accepted: 08/23/2013] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Probiotics are live microorganisms, which as drugs or food supplements help to maintain health beneficial microbial balance in the digestive tract of a human or other host. Probiotics by their properties may help strengthen homeostasis and thus reduce side effects associated with cancer treatment. Experimental evidence suggests that probiotics might have beneficial effect on the toxicity of anticancer therapy. METHODS A computer-based literature search was carried out using PubMed (keywords: "probiotic" and "lactic acid bacteria" in association with the search terms "cancer" or "oncology" or "chemotherapy" or "radiation"); data reported at international meetings were included. RESULTS Probiotics might have beneficial effects on some aspects of toxicity related to anticancer treatment especially radiation therapy. However, reported trials vary in utilized probiotic strains, dose of probiotics and vast majority of them are small trials with substantial risk of bias. Despite limited data, it seems that probiotic bacteria as live microorganisms could be safely administered even in the setting of neutropenia. CONCLUSIONS Current evidence supporting probiotic use as adjunctive therapy to anticancer treatment is limited, especially in cancer patients treated with chemotherapy. Well designed clinical trials are needed to find true role of probiotics in oncology.
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Affiliation(s)
- Michal Mego
- Department of Medical Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Klenova 1, 833 10 Bratislava, Slovak Republic.
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Kim BS, Jeon YS, Chun J. Current status and future promise of the human microbiome. Pediatr Gastroenterol Hepatol Nutr 2013; 16:71-9. [PMID: 24010110 PMCID: PMC3760697 DOI: 10.5223/pghn.2013.16.2.71] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2013] [Accepted: 06/05/2013] [Indexed: 12/11/2022] Open
Abstract
The human-associated microbiota is diverse, varies between individuals and body sites, and is important in human health. Microbes in human body play an essential role in immunity, health, and disease. The human microbiome has been studies using the advances of next-generation sequencing and its metagenomic applications. This has allowed investigation of the microbial composition in the human body, and identification of the functional genes expressed by this microbial community. The gut microbes have been found to be the most diverse and constitute the densest cell number in the human microbiota; thus, it has been studied more than other sites. Early results have indicated that the imbalances in gut microbiota are related to numerous disorders, such as inflammatory bowel disease, colorectal cancer, diabetes, and atopy. Clinical therapy involving modulating of the microbiota, such as fecal transplantation, has been applied, and its effects investigated in some diseases. Human microbiome studies form part of human genome projects, and understanding gleaned from studies increase the possibility of various applications including personalized medicine.
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Affiliation(s)
- Bong-Soo Kim
- Chunlab Inc., Seoul National University, Seoul, Korea
| | - Yoon-Seong Jeon
- Chunlab Inc., Seoul National University, Seoul, Korea
- Interdisciplinary Graduate Program in Bioinformatics, Seoul National University, Seoul, Korea
| | - Jongsik Chun
- Chunlab Inc., Seoul National University, Seoul, Korea
- Interdisciplinary Graduate Program in Bioinformatics, Seoul National University, Seoul, Korea
- School of Biological Sciences, Seoul National University, Seoul, Korea
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Vandenplas Y, De Greef E, Hauser B, Devreker T, Veereman-Wauters G. Probiotics and prebiotics in pediatric diarrheal disorders. Expert Opin Pharmacother 2013; 14:397-409. [PMID: 23406505 DOI: 10.1517/14656566.2013.771632] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
INTRODUCTION In pediatrics, prebiotics and/or probiotics are added to infant formula, mainly to prevent diseases such as diarrheal disorders. Probiotic food supplements and medication are frequently used in the treatment of diarrheal disorders. This paper reviews the recent published evidence on these topics. AREAS COVERED Relevant literature published using PubMed and CINAHL was collected and reviewed. Recent review papers were give special attention. EXPERT OPINION The addition of pre- and/or probiotics to infant formula seems not harmful, but the evidence for benefit is limited. Most probiotics are commercialized as food supplements, and therefore do not qualify for medication legislation. Worldwide, Saccharomyces boulardii is the only strain which is registered as "medication" in the majority of countries. Efficacy data can only be considered if performed with the commercialized product. Some products reduce the risk for antibiotic-associated diarrhea and reduced the duration of acute infectious diarrhea with about 24 h. Overall, data in the other indications (inflammatory bowel disease, irritable bowel syndrome) are disappointing, although there are some recent promising results. The use of food supplements as medication opens the discussion to create a category of "medical food."
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Affiliation(s)
- Y Vandenplas
- Vrije Universiteit Brussel, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
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West NP, Cripps AW. Are vaccination models suitable to determine whether probiotics have beneficial health effects in the general population? Hum Vaccin Immunother 2013; 9:621-4. [PMID: 23292093 DOI: 10.4161/hv.23254] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
The European Food Safety Authority (EFSA) has indicated that stimulation of protective antibody titers from vaccination could be used to substantiate a supplement or food health claim on the function of the immune system related to defense against pathogens in healthy individuals. Vaccination allows exposure of the immune system to controlled quantities of antigen and also for assessment of median antibody responses and percentage of responders/non-responders, which provides indication of an integrated immune response to challenge. Probiotic vaccination studies have shown enhanced antibody titers, lower percentages of non-seroconverters and greater percentages reaching minimum cut-off titer values in healthy adults, elderly and children. These results indicate that probiotics are a good candidate to stimulate responses to vaccines and thus, according to EFSA, enhance the function of the immune system related to defense against infection. However, animal research has recently indicated that Foxp3+ T-regulatory cells, recognized suppressors of immune activity, were paradoxically associated with reduced respiratory viral morbidity without compromising viral clearance. These effects conflict with vaccine research findings, which suggest a depletion of Foxp3+ T-regs enhances the immune response. Many probiotics exert anti-inflammatory influence on the immune system and induce T-regs. Given this, caution regarding the applicability of the vaccination model as indicated by EFSA must be exercised. Induction of T-cell immune modulatory pathways may also explain the reduced duration of respiratory illness observed in probiotic clinical studies.
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Affiliation(s)
- Nicholas P West
- Griffith Health Institute; School of Medicine; Griffith University; Nathan, QLD Australia
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Isolation of probiotic lactobacilli strains harboring l-asparaginase and arginine deiminase genes from human infant feces for their potential application in cancer prevention. ANN MICROBIOL 2012. [DOI: 10.1007/s13213-012-0569-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Piano MD, Carmagnola S, Ballarè M, Balzarini M, Montino F, Pagliarulo M, Anderloni A, Orsello M, Tari R, Sforza F, Mogna L, Mogna G. Comparison of the kinetics of intestinal colonization by associating 5 probiotic bacteria assumed either in a microencapsulated or in a traditional, uncoated form. J Clin Gastroenterol 2012; 46 Suppl:S85-92. [PMID: 22955366 DOI: 10.1097/mcg.0b013e3182672796] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Beneficial findings concerning probiotics are increasing day by day. However, one of the most important parameters able to significantly affect the probiotic value of a microorganism is its survival during the transit through the stomach and the duodenum. Some techniques may be applied that aim to improve this parameter, but microencapsulation of bacterial cells remains one of the most important. A recent study assessed the kinetics of intestinal colonization by a mixture of 2 probiotic strains, given either in a microencapsulated or in a traditional, uncoated form. METHODS A comparison between the intestinal colonization by associating 5 microencapsulated bacteria and the same uncoated strains was performed by a double-blind, randomized, cross-over study. The study (December 2007 to January 2009) involved 53 healthy volunteers. In particular, subjects were divided into 2 groups: group A (27 subjects) was given a mix of probiotic strains Probiotical S.p.A. (Novara, Italy), Lactobacillus acidophilus LA02 (DSM 21717), Lactobacillus rhamnosus LR04 (DSM 16605), L. rhamnosus GG, or LGG (ATCC 53103), L. rhamnosus LR06 (DSM 21981), and Bifidobacterium lactis BS01 (LMG P-21384) in an uncoated form, whereas group B (26 subjects) received the same strains microencapsulated with a gastroprotected material. The uncoated strains were administered at 5×10⁹ cfu/strain/d (a total of 25×10⁹ cfu/d) for 21 days, whereas the microencapsulated bacteria were given at 1×10⁹ cfu/strain/d (a total of 5×10⁹ cfu/d) for 21 days. At the end of the first period of supplementation with probiotics, a 3-week wash-out phase was included in the study setting. At the end of the wash-out period, the groups crossed over their treatment regimen; that is, group A was administered the microencapsulated bacteria and group B the uncoated bacteria. The administered quantities of each strain were the same as the first treatment. A quantitative evaluation of intestinal colonization by probiotics, either microencapsulated or uncoated, was undertaken by examining fecal samples at the beginning of the study (time 0), after 10 days and after 21 days of each treatment period. In particular, fecal total Lactobacilli, heterofermentative Lactobacilli, and total Bifidobacteria were quantified at each checkpoint. A genomic analysis of an appropriate number of colonies was performed to quantify individual L. rhamnosus strains among heterofermentative Lactobacilli. RESULTS A statistically significant increase in the fecal amounts of total Lactobacilli, heterofermentative Lactobacilli, and total Bifidobacteria was registered in both groups at the end of each supplementation period compared with d₀ or d₄₂ (group A: P=0.0002, P=0.0001, and P<0.0001 at d₂₁, P=0.0060, P=0.0069, and P<0.0001 at d₆₃ for total Lactobacilli, heterofermentative Lactobacilli, and Bifidobacteria, respectively; group B: P=0.0002, P=0.0006, and P<0.0001 at d₂₁, P=0.0015, P=0.0016, and P<0.0001 at d₆₃ for total Lactobacilli, heterofermentative Lactobacilli, and Bifidobacteria, respectively), confirming the ability of each strain in the administered composition to colonize the human gut, whether supplemented in a gastroprotected or in a traditional freeze-dried form. On the contrary, subjects receiving microencapsulated bacteria reported a kinetics of intestinal colonization that was entirely comparable with those who were given uncoated strains at a 5 times higher amount. CONCLUSIONS The microencapsulation technique used in this study is a valid approach aimed to significantly improve the survival of strains during gastroduodenal transit, thus enhancing their probiotic value and allowing the use of a 5 times lower amount.
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Affiliation(s)
- Mario D Piano
- Gastroenterology Unit, Maggiore della Carità Hospital, Corso Mazzini, Novara, Italy.
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Walker AW, Lawley TD. Therapeutic modulation of intestinal dysbiosis. Pharmacol Res 2012; 69:75-86. [PMID: 23017673 DOI: 10.1016/j.phrs.2012.09.008] [Citation(s) in RCA: 122] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2012] [Revised: 09/10/2012] [Accepted: 09/14/2012] [Indexed: 12/17/2022]
Abstract
The human gastrointestinal tract is home to an extremely numerous and diverse collection of microbes, collectively termed the "intestinal microbiota". This microbiota is considered to play a number of key roles in the maintenance of host health, including aiding digestion of otherwise indigestible dietary compounds, synthesis of vitamins and other beneficial metabolites, immune system regulation and enhanced resistance against colonisation by pathogenic microorganisms. Conversely, the intestinal microbiota is also a potent source of antigens and potentially harmful compounds. In health, humans can therefore be considered to exist in a state of natural balance with their microbial inhabitants. A shift in the balance of microbiota composition such that it may become deleterious to host health is termed "dysbiosis". Dysbiosis of the gut microbiota has been implicated in numerous disorders, ranging from intestinal maladies such as inflammatory bowel diseases and colorectal cancer to disorders with more systemic effects such as diabetes, metabolic syndrome and atopy. Given the far reaching influence of the intestinal microbiota on human health a clear future goal must be to develop reliable means to alter the composition of the microbiota and restore a healthy balance of microbial species. While it is clear that much fundamental research remains to be done, potentially important therapeutic options include narrow spectrum antibiotics, novel probiotics, dietary interventions and more radical techniques such as faecal transplantation, all of which aim to suppress clinical dysbiosis, restore intestinal microbiota diversity and improve host health.
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Affiliation(s)
- Alan W Walker
- Pathogen Genomics Group, Wellcome Trust Sanger Institute, Hinxton, UK.
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Zhang CD, Dai DQ, Zhao ZM. Probiotics for the prevention of antibiotic-associated diarrhea in adult patients: A meta-analysis. Shijie Huaren Xiaohua Zazhi 2012; 20:2006-2011. [DOI: 10.11569/wcjd.v20.i21.2006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To systematically investigate whether current clinical trails can clarify the association between probiotic administration and adult antibiotic-associated diarrhea (AAD), and to evaluate the efficacy and safety of probiotic administration in preventing AAD in both inpatient and outpatient adults.
METHODS: PubMed, Embase, CINAHL, AMED, the Cochrane database of Systematic Reviews, the Cochrane Controlled Trials Register, and the China National Knowledge Infrastructure (CNKI) electronic databases were searched for studies published between January 1966 and April 2012. Only prospective, randomized, controlled trials involving patients older than 18 years were included. Furthermore, only the trials which combined antibiotic administration and probiotic therapy for the prevention of AAD were extracted.
RESULTS: The data of the present study showed a significantly decreased risk of adult AAD: relative risk (RR) = 0.45, 95% confidence interval (CI), 0.29-0.69, P < 0.001. Similar results were obtained from the subgroup analysis of particular types of probiotics (RR = 0.42, 95%CI: 0.20-0.85, P = 0.003).
CONCLUSION: Our study suggests that adult patients can benefit from probiotics co-administered with antibiotics.
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Collado MC, Cernada M, Baüerl C, Vento M, Pérez-Martínez G. Microbial ecology and host-microbiota interactions during early life stages. Gut Microbes 2012; 3:352-65. [PMID: 22743759 PMCID: PMC3463493 DOI: 10.4161/gmic.21215] [Citation(s) in RCA: 183] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
The role of human microbiota has been redefined during recent years and its physiological role is now much more important than earlier understood. Intestinal microbial colonization is essential for the maturation of immune system and for the developmental regulation of the intestinal physiology. Alterations in this process of colonization have been shown to predispose and increase the risk to disease later in life. The first contact of neonates with microbes is provided by the maternal microbiota. Moreover, mode of delivery, type of infant feeding and other perinatal factors can influence the establishment of the infant microbiota. Taken into consideration all the available information it could be concluded that the exposure to the adequate microbes early in gestation and neonatal period seems to have a relevant role in health. Maternal microbial environment affects maternal and fetal immune physiology and, of relevance, this interaction with microbes at the fetal-maternal interface could be modulated by specific microbes administered to the pregnant mother. Indeed, probiotic interventions aiming to reduce the risk of immune-mediated diseases may appear effective during early life.
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Affiliation(s)
- Maria Carmen Collado
- Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Department of Biotechnology, Unit of Lactic Acid Bacteria and Probiotics, Valencia, Spain.
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40
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Ringel-Kulka T. Targeting the intestinal microbiota in the pediatric population: a clinical perspective. Nutr Clin Pract 2012; 27:226-34. [PMID: 22402406 DOI: 10.1177/0884533612439895] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The intestinal microbiota is a functional organ with a variety of important metabolic, trophic, immunologic, and digestive activities. Current data suggest that alterations in the intestinal microbiota may be related to disease conditions. Manipulation of the intestinal microbiota such as with probiotics, prebiotics, and synbiotics may be beneficial in preventing and treating certain disease conditions. This article provides an overview of the evidence gathered through randomized clinical trials, reviews, and meta-analyses on probiotics and prebiotics in commonly studied conditions in the pediatric population. It concludes with current recommendations for their use, noting safety and gaps in clinical evidence.
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Affiliation(s)
- Tamar Ringel-Kulka
- Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7445, USA.
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Abstract
AbstractProbiotika können bei verschiedenen Infektionen und chronischen Entzündungen des Magen‐Darm‐Traktes erfolgreich eingesetzt werden. Der folgende Artikel fasst die aktuelle Studienlage zusammen.
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Affiliation(s)
- Jürgen Stein
- Gastroenterologie/Diabetologie/Ernährungsmedizin, St. Elisabethen-Krankenhaus der Katharina Kasper Kliniken, Lehrkrankenhaus der J. W. Goethe-Universität Frankfurt, Ginnheimer Str. 3, 60487 Frankfurt/Main.
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42
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Lyme Disease. Integr Med (Encinitas) 2012. [DOI: 10.1016/b978-1-4377-1793-8.00022-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Wang X, Yang F, Liu C, Zhou H, Wu G, Qiao S, Li D, Wang J. Dietary supplementation with the probiotic Lactobacillus fermentum I5007 and the antibiotic aureomycin differentially affects the small intestinal proteomes of weanling piglets. J Nutr 2012; 142:7-13. [PMID: 22113866 DOI: 10.3945/jn.111.147074] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Antibiotics have long been used in animal production and medication to alleviate weaning stress. However, due to the concerns over food safety and human health, its use in animal production has been prohibited in many countries. Therefore, there is growing interest in developing alternative additives, such as a probiotic Lactobacillus. In this study, a proteomic approach coupled with biochemical analysis was applied to investigate alterations of proteomes in the small intestinal mucosa of weanling piglets after a 13-d period of feeding with supplemental L. fermentum I5007 or aureomycin (an antibiotic). We indentified 27 differentially expressed protein spots that participated in 7 key biological processes, including: 1) energy metabolism; 2) lipid metabolism; 3) protein synthesis; 4) cell structure and mobility; 5) cellular proliferation and apoptosis; 6) immune response; and 7) stress response and detoxification. Both L. fermentum I5007 and aureomycin decreased the expression of proteins related to apoptosis, stress response, and increased the expression of proteins related to detoxification in the gastrointestinal (GI) tract of weanling piglets. L. fermentum I5007 exhibited additional effects in alleviating weaning stress syndrome by enhancing the levels of proteins involved in energy metabolism, lipid metabolism, cell structure and mobility, protein synthesis, and immune response, thereby facilitating cellular proliferation and depressing apoptosis. In contrast, aureomycin reduced the levels of proteins related to energy metabolism, protein synthesis, cell structure, motility, and immunity. These novel findings have important implications for understanding the mechanisms whereby L. fermentum I5007 can improve the GI health of postweaning piglets.
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Affiliation(s)
- Xiaoqiu Wang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
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44
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Bron PA, van Baarlen P, Kleerebezem M. Emerging molecular insights into the interaction between probiotics and the host intestinal mucosa. Nat Rev Microbiol 2011; 10:66-78. [PMID: 22101918 DOI: 10.1038/nrmicro2690] [Citation(s) in RCA: 443] [Impact Index Per Article: 31.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Probiotic bacteria can modulate immune responses in the host gastrointestinal tract to promote health. The genomics era has provided novel opportunities for the discovery and characterization of bacterial probiotic effector molecules that elicit specific responses in the intestinal system. Furthermore, nutrigenomic analyses of the response to probiotics have unravelled the signalling and immune response pathways which are modulated by probiotic bacteria. Together, these genomic approaches and nutrigenomic analyses have identified several bacterial factors that are involved in modulation of the immune system and the mucosal barrier, and have revealed that a molecular 'bandwidth of human health' could represent a key determinant in an individual's physiological responsiveness to probiotics. These approaches may lead to improved stratification of consumers and to subpopulation-level probiotic supplementation to maintain or improve health, or to reduce the risk of disease.
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Affiliation(s)
- Peter A Bron
- Top Institute Food and Nutrition, Nieuwe Kanaal 9A, 6709 PA Wageningen, The Netherlands
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45
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Johnston BC, Goldenberg JZ, Vandvik PO, Sun X, Guyatt GH. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev 2011:CD004827. [PMID: 22071814 DOI: 10.1002/14651858.cd004827.pub3] [Citation(s) in RCA: 107] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Antibiotics alter the microbial balance within the gastrointestinal tract. Probiotics may prevent antibiotic-associated diarrhea (AAD) via restoration of the gut microflora. Antibiotics are prescribed frequently in children and AAD is common in this population. OBJECTIVES The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children. SEARCH METHODS MEDLINE, EMBASE, CENTRAL, CINAHL, AMED, and the Web of Science (inception to May 2010) were searched along with specialized registers including the Cochrane IBD/FBD review group, CISCOM (Centralized Information Service for Complementary Medicine), NHS Evidence, the International Bibliographic Information on Dietary Supplements as well as trial registries. Letters were sent to authors of included trials, nutra/pharmaceutical companies, and experts in the field requesting additional information on ongoing or unpublished trials. Conference proceedings, dissertation abstracts, and reference lists from included and relevant articles were also searched. SELECTION CRITERIA Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the incidence of diarrhea secondary to antibiotic use were considered for inclusion. DATA COLLECTION AND ANALYSIS Study selection, data extraction as well as methodological quality assessment using the risk of bias instrument was conducted independently and in duplicate by two authors. Dichotomous data (incidence of diarrhea, adverse events) were combined using a pooled relative risk and risk difference (adverse events), and continuous data (mean duration of diarrhea, mean daily stool frequency) as weighted mean differences, along with their corresponding 95% confidence intervals. For overall pooled results on the incidence of diarrhea, sensitivity analyses included available case versus extreme-plausible analyses and random- versus fixed-effect models. To explore possible explanations for heterogeneity, a priori subgroup analysis were conducted on probiotic strain, dose, definition of antibiotic-associated diarrhea, antibiotic agent as well as risk of bias. MAIN RESULTS Sixteen studies (3432 participants) met the inclusion criteria. Trials included treatment with either Bacillus spp., Bifidobacterium spp., Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., or Streptococcus spp., alone or in combination. Nine studies used a single strain probiotic agent, four combined two probiotic strains, one combined three probiotic strains, one product included ten probiotic agents, and one study included two probiotic arms that used three and two strains respectively. The risk of bias was determined to be high in 8 studies and low in 8 studies. Available case (patients who did not complete the studies were not included in the analysis) results from 15/16 trials reporting on the incidence of diarrhea show a large, precise benefit from probiotics compared to active, placebo or no treatment control. The incidence of AAD in the probiotic group was 9% compared to 18% in the control group (2874 participants; RR 0.52; 95% CI 0.38 to 0.72; I(2) = 56%). This benefit was not statistically significant in an extreme plausible (60% of children loss to follow-up in probiotic group and 20% loss to follow-up in the control group had diarrhea) intention to treat (ITT) sensitivity analysis. The incidence of AAD in the probiotic group was 16% compared to 18% in the control group (3392 participants; RR 0.81; 95% CI 0.63 to 1.04; I(2) = 59%). An a priori available case subgroup analysis exploring heterogeneity indicated that high dose (≥5 billion CFUs/day) is more effective than low probiotic dose (< 5 billion CFUs/day), interaction P value = 0.010. For the high dose studies the incidence of AAD in the probiotic group was 8% compared to 22% in the control group (1474 participants; RR 0.40; 95% CI 0.29 to 0.55). For the low dose studies the incidence of AAD in the probiotic group was 8% compared to 11% in the control group (1382 participants; RR 0.80; 95% CI 0.53 to 1.21). An extreme plausible ITT subgroup analysis was marginally significant for high dose probiotics. For the high dose studies the incidence of AAD in the probiotic group was 17% compared to 22% in the control group (1776 participants; RR 0.72; 95% CI 0.53 to 0.99; I(2) = 58%). None of the 11 trials (n = 1583) that reported on adverse events documented any serious adverse events. Meta-analysis excluded all but an extremely small non-significant difference in adverse events between treatment and control (RD 0.00; 95% CI -0.01 to 0.02). AUTHORS' CONCLUSIONS Despite heterogeneity in probiotic strain, dose, and duration, as well as in study quality, the overall evidence suggests a protective effect of probiotics in preventing AAD. Using 11 criteria to evaluate the credibility of the subgroup analysis on probiotic dose, the results indicate that the subgroup effect based on dose (≥5 billion CFU/day) was credible. Based on high-dose probiotics, the number needed to treat (NNT) to prevent one case of diarrhea is seven (NNT 7; 95% CI 6 to 10). However, a GRADE analysis indicated that the overall quality of the evidence for the primary endpoint (incidence of diarrhea) was low due to issues with risk of bias (due to high loss to follow-up) and imprecision (sparse data, 225 events). The benefit for high dose probiotics (Lactobacillus rhamnosus or Saccharomyces boulardii) needs to be confirmed by a large well-designed randomized trial. More refined trials are also needed that test strain specific probiotics and evaluate the efficacy (e.g. incidence and duration of diarrhea) and safety of probiotics with limited losses to follow-up. It is premature to draw conclusions about the efficacy and safety of other probiotic agents for pediatric AAD. Future trials would benefit from a standard and valid outcomes to measure AAD.
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Affiliation(s)
- Bradley C Johnston
- Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
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Vandenplas Y, De Hert SG. Randomised clinical trial: the synbiotic food supplement Probiotical vs. placebo for acute gastroenteritis in children. Aliment Pharmacol Ther 2011; 34:862-7. [PMID: 21899583 DOI: 10.1111/j.1365-2036.2011.04835.x] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Some probiotic strains reduce the duration of acute diarrhoea. As a result of strain and product specificity, each product needs support by clinical data. AIM In children with acute diarrhoea, to test the efficacy of the synbiotic food supplement Probiotical (Streptoccoccus thermophilus, Lactobacillus rhamnosus, Lactobacillus acidophilus, Bifidobacterium lactis, Bifidobacterium infantis, fructo-oligosaccharides). The primary end-points were duration of diarrhoea and the number of children that had a normalised stool consistency. METHOD A total of 111 children with acute diarrhoea (median age 40 months) were included in this randomised, prospective placebo-controlled parallel clinical trial in primary health care. All children were treated with oral rehydration solution ad libitum and with the synbiotic (n=57) or placebo (n = 54). RESULTS The median duration of diarrhoea was 3 days (IQ 25-75: 2-4 days) in the Probiotical group, compared with 4 days (IQ 25-75: 4-5 days) in the placebo group (P<0.005). The number of children with normal stool consistency (defined as stool Bristol score ≤4) was higher in the synbiotic group on days 2 and 3 [21 vs. 2% (P<0.001) and 50 vs. 24% (P<0.001) respectively]. Less additional medication (antipyretics, antiemetics, antibiotics) was administered in the synbiotic group. Physicians were globally more satisfied with the synbiotic food supplement treatment than with placebo (P=0.005). One patient in the placebo group was hospitalised. CONCLUSION The median duration of diarrhoea was significantly 1 day shorter in the synbiotic than in the placebo group, associated with decreased prescription of additional medications.
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Affiliation(s)
- Y Vandenplas
- Universitair KinderZiekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
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47
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Gibson GR, Brummer RJ, Isolauri E, Lochs H, Morelli L, Ockhuizen T, Rowland IR, Schrezenmeir J, Stanton C, Verbeke K. The design of probiotic studies to substantiate health claims. Gut Microbes 2011; 2:299-305. [PMID: 22067941 DOI: 10.4161/gmic.2.5.18002] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
The EC Regulation No. 1924/2006 on Nutrition and Health claims made on foods has generated considerable debate and concern among scientists and industry. At the time of writing, the European Food Safety Authority (EFSA) has not approved any probiotic claims despite numerous human trials and meta-analyses showing evidence of beneficial effects. On 29th and 30th September 2010, ten independent, academic scientists with a documented record in probiotic research, met to discuss designs for future probiotic studies to demonstrate health benefits for gut and immune function. The expert panel recommended the following: (i) always formulate a precise and concrete hypothesis, and appropriate goals and parameters before starting a trial; (ii) ensure trials have sufficient sample size, such that they are adequately powered to reach statistically significant conclusions, either supporting or rejecting the a priori hypothesis, taking into account adjustment for multiple testing (this might necessitate more than one recruitment site); (iii) ensure trials are of appropriate duration; (iv) focus on a single, primary objective and only evaluate multiple parameters when they are hypothesis-driven. The panel agreed that there was an urgent need to better define which biomarkers are considered valuable for substantiation of a health claim. As a first step, the panel welcomed the publication on the day of the meeting of EFSA's draft guidance document on immune and gut health, although it came too late for study designs and dossiers to be adjusted accordingly. New validated biomarkers need to be identified in order to properly determine the range of physiological functions influenced by probiotics. In addition, validated biomarkers reflecting risk factors for disease, are required for article 14 claims (EC Regulation No. 1924/2006). Finally, the panel concluded that consensus among scientists is needed to decide appropriate clinical endpoints for trials.
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Affiliation(s)
- Glenn R Gibson
- Department of Food and Nutritional Sciences, University of Reading, Reading, UK
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48
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Wilhelm SM, Johnson JL, Kale-Pradhan PB. Treating Bugs with Bugs: The Role of Probiotics as Adjunctive Therapy for Helicobacter pylori. Ann Pharmacother 2011; 45:960-6. [DOI: 10.1345/aph.1q104] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Objective: To review the literature on the role of probiotics as adjunctive therapy in the treatment of Helicobacter pylori infections. Data Sources: Literature was accessed through MEDLINE (1966-March 2011) using the terms H. pylori, probiotic, Lactobacillus, Bifidobacterium, Saccharomyces, Bacillus clausii, and Propionibacterium. Article references were hand-searched for additional relevant articles and abstracts. Study Selection and Data Extraction: All English-language articles published in full were evaluated. Randomized, double-blind, placebo-controlled trials assessing the use of probiotics combined with standard eradication therapy of H. pylori infection in adults were included in the review. Data Synthesis: Various probiotics, including Lactobacillus spp., Saccharomyces spp., Bifidobacterium spp., and B. clausii, reduce adverse effects such as nausea, taste disturbance, diarrhea, and epigastric pain, and increase tolerability of H. pylori eradication therapy. Based on the studies reviewed, probiotics do not affect H. pylori eradication rates. Conclusions: Probiotics may be beneficial in reducing adverse effects and increasing tolerability of H. pylori eradication regimens. They may especially be helpful in patients with recurrent H. pylori infection and a history of gastrointestinal adverse effects with antibiotics. Pharmacists can play an important role in educating patients regarding probiotic use during H. pylori eradication therapy.
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Affiliation(s)
- Sheila M Wilhelm
- Wayne State University, and Harper University Hospital, Detroit, MI
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Zaharoni H, Rimon E, Vardi H, Friger M, Bolotin A, Shahar DR. Probiotics improve bowel movements in hospitalized elderly patients--the PROAGE study. J Nutr Health Aging 2011; 15:215-20. [PMID: 21369670 DOI: 10.1007/s12603-010-0323-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
OBJECTIVE To determine the impact of probiotics on the prevention of problems with bowel movements malnutrition and infection. DESIGN A randomized, double-blind, placebo-controlled trial. SETTING Peripheral Geriatric Hospital. PARTICIPANTS 243 elderly patients age ≥ 65 y who were hospitalized in a Geriatric Orthopedic Rehabilitation Department. INTERVENTION Participants were randomized into treatment or control groups (daily probiotics or placebo for 45 consecutive days, respectively). MEASUREMENTS The main outcomes were: number of days of constipation or diarrhea and the number of days of laxative use. Secondary measures were nutritional status and blood measurements. RESULTS Of 599 patients admitted to the Geriatric Rehabilitation ward, 345 were eligible and agreed to participate. During a 7-day pre-trial period, 102 patients dropped out (45 and 57 in the probiotic and placebo groups respectively). Out of the 243 patients who entered the study, 28 dropped out during the study (11.5%), leaving 215 patients. Throughout the 45 days of follow-up, the incidence of diarrhea was significantly lower among the study group (HR=0.42, p=0.04) with a more pronounced difference among participants aged ≥ 80 y (HR=0.32, p=0.026). Laxative use (as an indicator of constipation severity) was significantly lower in the study group compared with the control group (HR=0.74, p=0.032). Serum albumin, prealbumin and protein increased significantly more in the treatment group compared with the control group among participants age ≥ 80 y (P=0.047, p=0.07, p=0.03 respectively) but not in the younger age group. CONCLUSION We showed that probiotic supplements may have a positive effect on bowel movements among orthopedic rehabilitation elderly patients.
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Affiliation(s)
- H Zaharoni
- Harzfeld Geriatric Medical Center, Gedera, 70750 Israel.
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50
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Abstract
Antibiotics have been used effectively as a means to treat bacterial infections in humans and animals for over half a century. However, through their use, lasting alterations are being made to a mutualistic relationship that has taken millennia to evolve: the relationship between the host and its microbiota. Host-microbiota interactions are dynamic; therefore, changes in the microbiota as a consequence of antibiotic treatment can result in the dysregulation of host immune homeostasis and an increased susceptibility to disease. A better understanding of both the changes in the microbiota as a result of antibiotic treatment and the consequential changes in host immune homeostasis is imperative, so that these effects can be mitigated.
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