1
|
Jiang YZ, Ma K, Cui C, Li ZY, Wang XY. Effect of Saccharomyces boulardii supplementation to bismuth quadruple therapy on Helicobacter pylori eradication. BMC Gastroenterol 2025; 25:273. [PMID: 40251486 PMCID: PMC12008914 DOI: 10.1186/s12876-025-03879-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 04/10/2025] [Indexed: 04/20/2025] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection is a common chronic infection, and there are over half of the global population infected with H. pylori. It is still controversial whether the supplementation of Saccharomyces boulardii (S. boulardii) to bismuth quadruple therapy is beneficial for H. pylori eradication. AIM To determine the effects of S. boulardii supplementation to bismuth quadruple therapy on H. pylori eradication. METHODS We performed a systematic literature search across PubMed, Embase, Web of Science, and China National Knowledge Infrastructure for articles published up to October 2023. We calculated the pooled relative risk (RR) with the 95% confidence interval (CI). Statistical analyses were conducted using Stata/SE 15.1 software. RESULTS Ten randomized controlled trials were included. Notably, S. boulardii supplementation to bismuth quadruple therapy significantly improved H. pylori eradication rates (RR = 1.08, 95% CI: 1.04-1.12) and reduced the incidence of total adverse effects (RR = 0.53, 95% CI: 0.45-0.62). Specifically, it reduced the incidence of some gastrointestinal adverse effects and nonspecific adverse effects, including diarrhea (RR = 0.28, 95% CI: 0.22-0.36), constipation (RR = 0.32, 95% CI: 0.18-0.55), abdominal distention (RR = 0.39, 95% CI: 0.26-0.59), nausea (RR = 0.59, 95% CI: 0.36-0.97), and rash (RR = 0.49, 95% CI: 0.28-0.86). In the subgroup analysis, long-term eradication duration (> 10 days; RR = 1.08, 95% CI: 1.04-1.13) and S. boulardii supplementation to be started and stopped at the same time as eradication treatment (RR = 1.09, 95% CI: 1.04-1.14) were found to significantly improve the eradication rate regardless of the S. boulardii dose (500 mg/day, RR = 1.10, 95% CI: 1.03-1.17; 1000 mg/day, RR = 1.08, 95% CI: 1.03-1.12). CONCLUSIONS The addition of S. boulardii to bismuth quadruple therapy significantly increased H. pylori eradication rates and decreased the adverse effects. We recommend adding 500 mg/day S. boulardii concurrently with bismuth quadruple therapy and continuing this therapy for > 10 days for optimal H. pylori eradication efficacy.
Collapse
Affiliation(s)
- Yi-Zhou Jiang
- Department of Gastroenterology, Changzhou Medical Center, The Third Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, 68 Gehu middle road, Wujing District, Changzhou, Jiangsu Province, 213000, China
| | - Kai Ma
- Department of Gastroenterology, Changzhou Medical Center, The Third Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, 68 Gehu middle road, Wujing District, Changzhou, Jiangsu Province, 213000, China
| | - Cheng Cui
- Department of Gastroenterology, Changzhou Medical Center, The Third Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, 68 Gehu middle road, Wujing District, Changzhou, Jiangsu Province, 213000, China
| | - Zhuo-Ya Li
- Department of Gastroenterology, Changzhou Medical Center, The Third Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, 68 Gehu middle road, Wujing District, Changzhou, Jiangsu Province, 213000, China
| | - Xiao-Yong Wang
- Department of Gastroenterology, Changzhou Medical Center, The Third Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, 68 Gehu middle road, Wujing District, Changzhou, Jiangsu Province, 213000, China.
| |
Collapse
|
2
|
Fneish FH, Abd El Galil KH, Domiati SA. Evaluation of Single and Multi-Strain Probiotics with Gentamicin Against E. coli O157:H7: Insights from In Vitro and In Vivo Studies. Microorganisms 2025; 13:460. [PMID: 40005825 PMCID: PMC11858083 DOI: 10.3390/microorganisms13020460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Revised: 02/09/2025] [Accepted: 02/16/2025] [Indexed: 02/27/2025] Open
Abstract
The emergence of antibiotic-resistant food-borne pathogens, especially Escherichia coli O157:H7, highlights the urgent need for innovative treatment strategies, particularly in light of rising resistances and the ongoing controversy surrounding antibiotic use in response to E. coli O157:H7 infections. To address this issue, we explored the potential of single- and multi-strain probiotics, both independently and in combination with gentamicin, through a series of in vitro and in vivo experiments. In vitro, gentamicin alone produced a mean inhibition zone of 12.9 ± 2.27 mm against E. coli O157:H7. The combination of gentamicin with single-strain probiotics (P1) increased the inhibition zone to 16.5 ± 2.24 mm (p < 0.05), while the combination with multi-strain probiotics (P2) resulted in the largest inhibition zone of 19 ± 2.8 mm (p < 0.05). In vivo, mice infected with E. coli O157:H7 and treated with P2, gentamicin (G), or their combination (G+P2), achieved 100% survival, no pathological symptoms, and full weight recovery within seven days. Conversely, mice treated with P1 or G+P1 exhibited lower survival rates (71.4% and 85%, respectively) and slower weight recovery. Hematological parameters improved across all groups, but kidney function analysis showed significantly higher serum creatinine levels in the P1, G, G+P1, and G+P2 groups compared to the P2 group (P1: 0.63 ± 0.15 mg/dL; G: 0.34 ± 0.09 mg/dL; G+P1: 0.53 ± 0.19 mg/dL; G+P2: 0.5 ± 0.23 mg/dL vs. P2: 0.24 ± 0.2 mg/dL). Histological analysis showed better intestinal and kidney tissue recovery in the P2 group, while the P1 and G+P1 groups exhibited abnormal ileal structures and severe cortical bleeding. These findings highlight the promise of multi-strain probiotics, alone or in conjunction with antibiotics, as a therapeutic strategy for E. coli O157:H7 infections. However, the nephrotoxicity associated with gentamicin co-administration remains a limitation, warranting further studies to optimize this approach.
Collapse
Affiliation(s)
- Fatima H. Fneish
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Beirut Arab University, Riad El Solh P.O. Box 11-5020, Beirut 11072809, Lebanon
| | - Khaled H. Abd El Galil
- Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt;
| | - Souraya A. Domiati
- Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Beirut Arab University, Beirut 11072809, Lebanon;
| |
Collapse
|
3
|
Li M, Xie Y. Efficacy and safety of Saccharomyces boulardii as an adjuvant therapy for the eradication of Helicobacter pylori: a meta-analysis. Front Cell Infect Microbiol 2025; 15:1441185. [PMID: 40012609 PMCID: PMC11860874 DOI: 10.3389/fcimb.2025.1441185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 01/15/2025] [Indexed: 02/28/2025] Open
Abstract
Background Helicobacter pylori (H. pylori) is highly prevalent worldwide and is closely associated with many gastric conditions. Current methods for eradicating H. pylori include triple or quadruple therapy, including antibiotics, proton pump inhibitors, and bismuth agents; however, with antibiotic abuse and increased drug resistance rates, the effectiveness of traditional methods is gradually decreasing, with many adverse effects such as abdominal pain, diarrhea, and intolerance. In recent years, there has been controversy regarding whether adding Saccharomyces boulardii (S. boulardii) to traditional therapies is beneficial for eradicating H. pylori. Aim To evaluate the efficacy and safety of S. boulardii as an adjuvant therapy for the eradication of H. pylori. Methods We systematically searched the PubMed and Web of Science databases from January 2002 to January 2023. The primary outcome was the H. pylori eradication rate. The secondary outcomes included total adverse effects, abdominal pain, diarrhea, bloating, constipation, nausea, vomiting, taste disorders, and other adverse reactions. We evaluated the included studies for publication bias and heterogeneity. Fixed- and random-effects models were used for studies without and with heterogeneity, respectively, to calculate the risk ratios (RRs) and conduct sensitivity and subgroup analyses. Results Nineteen studies comprising 5,036 cases of H. pylori infection were included in this meta-analysis. The addition of S. boulardii to traditional therapy significantly improved the H. pylori eradication rate [RR=1.11, 95% confidence interval (CI): 1.08-1.15] and reduced the incidence of total adverse effects (RR=0.49, 95% CI: 0.37-0.66), diarrhea (RR=0.36, 95% CI: 0.26-0.48), abdominal distension (RR=0.49, 95% CI: 0.33-0.72), constipation (RR=0.38, 95% CI: 0.26-0.57), and nausea (RR=0.50, 95% CI: 0.37-0.68). However, it did not reduce the occurrence of abdominal pain, vomiting, or taste disorders. Conclusions S. boulardii supplementation in traditional eradication therapy significantly improves the H. pylori eradication rate and reduces the total adverse effects and incidence of diarrhea, bloating, constipation, and nausea. Systematic review registration Prospero, identifier CRD42024549780.
Collapse
Affiliation(s)
| | - Ying Xie
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| |
Collapse
|
4
|
Zhang H, Nuermaimaiti Y, Hao K, Qi Y, Xu Y, Zhuang Y, Wang F, Hou G, Chen T, Xiao J, Guo G, Wang Y, Li S, Cao Z, Liu S. Supplementation with Combined Additive Improved the Production of Dairy Cows and Their Offspring with Maintenance of Antioxidative Stability. Antioxidants (Basel) 2024; 13:650. [PMID: 38929089 PMCID: PMC11200508 DOI: 10.3390/antiox13060650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 05/21/2024] [Accepted: 05/23/2024] [Indexed: 06/28/2024] Open
Abstract
Oxidative stress damage in periparturient cows decreases both production and their health; supplementation with complex additives during the periparturient period has been used as an important strategy to enhance the antioxidant status and production of dairy cows. The periparturient cows not only risk a negative energy balance due to reduced dry matter intake but also represent a sensitive period for oxidative stress. Therefore, we have developed an immunomodulatory and nutritional regulation combined additive (INC) that hopefully can improve the immune status and production of cows during the periparturient period and their offspring health and growth by improving their antioxidant stress status. The INC comprised a diverse array of additives, including water-soluble and fat-soluble vitamins, Selenomethionine, and active dry Saccharomyces cerevisiae. Forty-five multiparous Holstein cows were randomly assigned to three treatments: CON (no INC supplementation, n = 15), INC30 (30 g/d INC supplementation, n = 15), and INC60 (60 g/d INC supplementation, n = 15) based on last lactation milk yield, body condition score, and parity. Newborn calves were administered 4 L of maternal colostrum originating from the corresponding treatment and categorized based on the treatment received by their respective dams. The INC not only served to maintain the antioxidative stress system of dairy cows during the periparturient period but also showed a tendency to improve the immune response (lower tumor necrosis factor and interleukin-6) during the perinatal period. A linear decrease in concentrations of alkaline phosphatase postpartum and β-hydroxybutyrate was observed with INC supplementation. Milk fat yield, milk protein yield, and energy-corrected milk yield were also increased linearly with increasing additive supplementation. Calves in the INC30 group exhibited greater wither height and chest girth but no significant effect on average daily gain or body weight. The diarrhea frequency was linearly decreased with the incremental level of INC. Results indicate that supplementation with INC in peripartum dairy cows could be a major strategy to improve immune response, decrease inflammation, maintain antioxidant stress status in transition dairy cows, and have merit in their calves. In conclusion, this study underlines the benefits of INC supplementation during the transition period, as it improved anti-inflammatory capacity, could positively impact antioxidative stress capacity, and eventually enhanced the production performance of dairy cows and the health and growth of calves.
Collapse
Affiliation(s)
- Hongxing Zhang
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (H.Z.); (Y.N.); (Y.X.); (Y.Z.); (F.W.); (G.H.); (T.C.); (J.X.); (Y.W.); (S.L.); (Z.C.)
| | - Yiliyaer Nuermaimaiti
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (H.Z.); (Y.N.); (Y.X.); (Y.Z.); (F.W.); (G.H.); (T.C.); (J.X.); (Y.W.); (S.L.); (Z.C.)
| | - Kebi Hao
- Beijing Sunlon Livestock Development Co., Ltd., Beijing 100176, China; (K.H.); (G.G.)
| | - Yan Qi
- China Animal Husbandry Group, Beijing 100070, China;
| | - Yiming Xu
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (H.Z.); (Y.N.); (Y.X.); (Y.Z.); (F.W.); (G.H.); (T.C.); (J.X.); (Y.W.); (S.L.); (Z.C.)
- College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China
| | - Yimin Zhuang
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (H.Z.); (Y.N.); (Y.X.); (Y.Z.); (F.W.); (G.H.); (T.C.); (J.X.); (Y.W.); (S.L.); (Z.C.)
| | - Fei Wang
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (H.Z.); (Y.N.); (Y.X.); (Y.Z.); (F.W.); (G.H.); (T.C.); (J.X.); (Y.W.); (S.L.); (Z.C.)
- College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China
| | - Guobin Hou
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (H.Z.); (Y.N.); (Y.X.); (Y.Z.); (F.W.); (G.H.); (T.C.); (J.X.); (Y.W.); (S.L.); (Z.C.)
- College of Animal Science and Technology, Beijing University of Agriculture, Beijing 102206, China
| | - Tianyu Chen
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (H.Z.); (Y.N.); (Y.X.); (Y.Z.); (F.W.); (G.H.); (T.C.); (J.X.); (Y.W.); (S.L.); (Z.C.)
| | - Jianxin Xiao
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (H.Z.); (Y.N.); (Y.X.); (Y.Z.); (F.W.); (G.H.); (T.C.); (J.X.); (Y.W.); (S.L.); (Z.C.)
| | - Gang Guo
- Beijing Sunlon Livestock Development Co., Ltd., Beijing 100176, China; (K.H.); (G.G.)
| | - Yajing Wang
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (H.Z.); (Y.N.); (Y.X.); (Y.Z.); (F.W.); (G.H.); (T.C.); (J.X.); (Y.W.); (S.L.); (Z.C.)
| | - Shengli Li
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (H.Z.); (Y.N.); (Y.X.); (Y.Z.); (F.W.); (G.H.); (T.C.); (J.X.); (Y.W.); (S.L.); (Z.C.)
| | - Zhijun Cao
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (H.Z.); (Y.N.); (Y.X.); (Y.Z.); (F.W.); (G.H.); (T.C.); (J.X.); (Y.W.); (S.L.); (Z.C.)
| | - Shuai Liu
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (H.Z.); (Y.N.); (Y.X.); (Y.Z.); (F.W.); (G.H.); (T.C.); (J.X.); (Y.W.); (S.L.); (Z.C.)
| |
Collapse
|
5
|
Yadav A, Yadav R, Sharma V, Dutta U. A comprehensive guide to assess gut mycobiome and its role in pathogenesis and treatment of inflammatory bowel disease. Indian J Gastroenterol 2024; 43:112-128. [PMID: 38409485 DOI: 10.1007/s12664-023-01510-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 12/20/2023] [Indexed: 02/28/2024]
Abstract
Inflammatory bowel disease (IBD) is an immune mediated chronic inflammatory disorder of gastrointestinal tract, which has underlying multifactorial pathogenic determinants such as environmental factors, susceptibility genes, gut microbial dysbiosis and a dysregulated immune response. Human gut is a frequent inhabitant of complex microbial ecosystem encompassing bacteria, viruses, parasites, fungi and other microorganisms that have an undisputable role in maintaining balanced homeostasis. All of these microbes interact with immune system and affect human gut physiology either directly or indirectly with interaction of each other. Intestinal fungi represent a smaller but crucial component of the human gut microbiome. Besides interaction with bacteriome and virome, it helps in balancing homoeostasis between pathophysiological and physiological processes, which is often dysregulated in patients with IBD. Understanding of gut mycobiome and its clinical implications are still in in its infancy as opposed to bacterial component of gut microbiome, which is more often focused. Modulation of gut mycobiome represents a novel and promising strategy in the management of patients with IBD. Emerging mycobiome-based therapies such as diet interventions, fecal microbiota transplantation (FMT), probiotics (both fungal and bacterial strains) and antifungals exhibit substantial effects in calibrating the gut mycobiome and restoring dysbalanced immune homeostasis by restoring the core gut mycobiome. In this review, we summarized compositional and functional diversity of the gut mycobiome in healthy individuals and patients with IBD, gut mycobiome dysbiosis in patients with IBD, host immune-fungal interactions and therapeutic role of modulation of intestinal fungi in patients with IBD.
Collapse
Affiliation(s)
- Amit Yadav
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Renu Yadav
- Department of Microbiology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Vishal Sharma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Usha Dutta
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India.
| |
Collapse
|
6
|
Liu LH, Han B, Tao J, Zhang K, Wang XK, Wang WY. The effect of Saccharomyces boulardii supplementation on Helicobacter pylori eradication in children: a systematic review and meta-analysis of Randomized controlled trials. BMC Infect Dis 2023; 23:878. [PMID: 38102568 PMCID: PMC10722661 DOI: 10.1186/s12879-023-08896-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 12/12/2023] [Indexed: 12/17/2023] Open
Abstract
BACKGROUND It is unclear whether Saccharomyces boulardii (S. boulardii) supplementation in standard triple therapy (STT) is effective in eradicating Helicobacter pylori (H. pylori) infection in children. We therefore conducted a meta-analysis of randomized controlled trials (RCTs) to assess the effect of S. boulardii supplementation on H. pylori eradication in children. METHODS We conducted electronic searches in PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure and Wanfang database from the beginning up to September 2023. A random-effects model was employed to calculate the pooled relative risk (RR) with 95% confidence intervals (CI) through a meta-analysis. RESULTS Fifteen RCTs (involving 2156 patients) were included in our meta-analysis. Results of the meta-analysis indicated that S. boulardii in combination with STT was more effective than STT alone (intention-to-treat analysis : 87.7% vs. 75.9%, RR = 1.14, 95% CI: 1.10-1.19, P < 0.00001; per-protocol analysis : 88.5% vs. 76.3%, RR = 1.15, 95% CI: 1.10-1.19, P < 0.00001). The S. boulardii supplementation group had a significantly lower incidence of total adverse events (n = 6 RCTs, 9.2% vs. 29.2%, RR = 0.32, 95% CI: 0.21-0.48, P < 0.00001), diarrhea (n = 13 RCTs, 14.7% vs. 32.4%, RR = 0.46, 95% CI: 0.37-0.56, P < 0.00001), and nausea (n = 11 RCTs, 12.7% vs. 21.3%, RR = 0.53, 95% CI: 0.40-0.72, P < 0.0001) than STT group alone. Similar results were also observed in the incidence of vomiting, constipation, abdominal pain, abdominal distention, epigastric discomfort, poor appetite and stomatitis. CONCLUSIONS Current evidence indicated that S. boulardii supplementing with STT could improve the eradication rate of H. pylori, and concurrently decrease the incidence of total adverse events and gastrointestinal adverse events in children.
Collapse
Affiliation(s)
- Lian-Hua Liu
- Department of Pediatric Gastroenterology, Guizhou Branch of Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Guizhou provincial people's hospital, Guiyang, Guizhou Province, China.
| | - Bin Han
- Department of Endoscopy, Guizhou Branch of Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Guizhou provincial people's hospital, Guiyang, Guizhou Province, China
| | - Jing Tao
- Department of Pediatric Gastroenterology, Guizhou Branch of Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Guizhou provincial people's hospital, Guiyang, Guizhou Province, China
| | - Kai Zhang
- Department of Pediatric Gastroenterology, Guizhou Branch of Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Guizhou provincial people's hospital, Guiyang, Guizhou Province, China
| | - Xi-Ke Wang
- Department of Pediatric Gastroenterology, Guizhou Branch of Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Guizhou provincial people's hospital, Guiyang, Guizhou Province, China
| | - Wen-Yu Wang
- Department of Pediatric Gastroenterology, Guizhou Branch of Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, 395 Jinzhu East Road, Guanshanhu District, Guiyang City, Guizhou Province, China.
| |
Collapse
|
7
|
Gowen R, Gamal A, Di Martino L, McCormick TS, Ghannoum MA. Modulating the Microbiome for Crohn's Disease Treatment. Gastroenterology 2023; 164:828-840. [PMID: 36702360 PMCID: PMC10152883 DOI: 10.1053/j.gastro.2023.01.017] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 12/12/2022] [Accepted: 01/06/2023] [Indexed: 01/28/2023]
Abstract
The central role of the gut microbiota in the regulation of health and disease has been convincingly demonstrated. Polymicrobial interkingdom interactions between bacterial (the bacteriome) and fungal (the mycobiome) communities of the gut have become a prominent focus for development of potential therapeutic approaches. In addition to polymicrobial interactions, the complex gut ecosystem also mediates interactions between the host and the microbiota. These interactions are complex and bidirectional; microbiota composition can be influenced by host immune response, disease-specific therapeutics, antimicrobial drugs, and overall ecosystems. However, the gut microbiota also influences host immune response to a drug or therapy by potentially transforming the drug's structure and altering bioavailability, activity, or toxicity. This is especially true in cases where the gut microbiota has produced a biofilm. The negative ramifications of biofilm formation include alteration of gut permeability, enhanced antimicrobial resistance, and alteration of host immune response effectiveness. Natural modulation of the gut microbiota, using probiotic and prebiotic approaches, may also be used to affect the host microbiome, a type of "natural" modulation of the host microbiota composition. In this review, we discuss potential bidirectional interactions between microbes and host, and we describe the changes in gut microbiota induced by probiotic and prebiotic approaches as well as their potential clinical consequences, including biofilm formation. We outline a systematic approach to designing probiotics capable of altering the host microbiota in disease states, using Crohn's disease as a model chronic disease. Understanding how the effective changes in the microbiome may enhance treatment efficacy may unlock the possibility of modulating the gut microbiome to improve treatment using a natural approach.
Collapse
Affiliation(s)
- Rachael Gowen
- Department of Dermatology, Case Western Reserve University, Cleveland, Ohio; University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Ahmed Gamal
- Department of Dermatology, Case Western Reserve University, Cleveland, Ohio; University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Luca Di Martino
- University Hospitals Cleveland Medical Center, Cleveland, Ohio; Department of Medicine, Case Western Reserve University, Cleveland, Ohio; Case Digestive Health Research Institute, Case Western Reserve University, Cleveland Ohio
| | - Thomas S McCormick
- Department of Dermatology, Case Western Reserve University, Cleveland, Ohio; University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Mahmoud A Ghannoum
- Department of Dermatology, Case Western Reserve University, Cleveland, Ohio; University Hospitals Cleveland Medical Center, Cleveland, Ohio.
| |
Collapse
|
8
|
He XJ, Wang XL, Sun DJ, Huang XY, Liu G, Li DZ, Lin HL, Zeng XP, Li DL, Wang W. The efficacy and safety of Saccharomyces boulardii in addition to antofloxacin-based bismuth quadruple therapy for Helicobacter pylori eradication: a single-center, prospective randomized-control study. Therap Adv Gastroenterol 2023; 16:17562848221147763. [PMID: 36742013 PMCID: PMC9893347 DOI: 10.1177/17562848221147763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 12/11/2022] [Indexed: 01/30/2023] Open
Abstract
Background We previously reported that antofloxacin-based bismuth quadruple therapy was safe and effective for Helicobacter pylori (H. pylori) eradication. It is not clear whether the addition of Saccharomyces boulardii (S. boulardii) to antofloxacin-based quadruple therapy can improve the eradication rate of H. pylori and reduce adverse events. Objective To investigate the effect of adding S. boulardii to antofloxacin-based quadruple therapy on the eradication rate of H. pylori and the adverse events. Design Single-center, prospective randomized controlled study. Methods A total of 172 patients with H. pylori infection were randomly assigned to the test and control groups. Patients in the control group (n = 86) received antofloxacin-based bismuth quadruple therapy for 14 days. On this basis, cases in the test group (n = 86) received S. boulardii 500 mg b.i.d. The eradication rate of H. pylori and adverse events were observed 4 weeks after the treatment. Results There were no statistically significant differences in the eradication rates of H. pylori and frequency of diarrhea between the test group and control group (p > 0.05). The duration of diarrhea in the test group was significantly shorter than in the control group (p < 0.001). In addition, the two groups exhibited similar adverse event rates for epigastric pain, abdominal distention, dizzy, vomiting, and rash (p > 0.05). The severity of adverse reactions was similar between the two groups (p > 0.05), and most of them had mild adverse events. Conclusion Although the addition of S. boulardii to antofloxacin-based quadruple therapy could not improve the eradication rate of H. pylori, it could shorten the time of antibiotic-associated diarrhea and reduce the incidence of diarrhea. Trial registration number ChiCTR2200056931.
Collapse
Affiliation(s)
- Xiao-Jian He
- Department of Digestive Diseases, Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, Fuzhou, China
| | - Xiao-Ling Wang
- Department of Digestive Diseases, Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, Fuzhou, China
| | - Dong-Jie Sun
- Department of Digestive Diseases, Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, Fuzhou, China
| | - Xiao-Yan Huang
- Department of Oncology, 900TH Hospital of Joint Logistics Support Force, Fuzhou, China
| | - Gang Liu
- Department of Digestive Diseases, Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, Fuzhou, China
| | - Da-Zhou Li
- Department of Digestive Diseases, Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, Fuzhou, China
| | - Hai-Lan Lin
- Department of Digestive Diseases, Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, Fuzhou, China
| | - Xiang-Peng Zeng
- Department of Digestive Diseases, Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, 156 North Road of West No.2 Ring, Fuzhou 350025, China
| | - Dong-Liang Li
- Department of Digestive Diseases, Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Diseases, 900TH Hospital of Joint Logistics Support Force, 156 North Road of West No.2 Ring, Fuzhou 350025, China
| | - Wen Wang
- Department of Digestive Diseases, Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, 156 North Road of West No.2 Ring, Fuzhou 350025, China
| |
Collapse
|
9
|
Hiltz R, Steelreath M, Degenshein-Woods M, Hung H, Aguilar A, Nielsen H, Rezamand P, Laarman A. Effects of Saccharomyces cerevisiae boulardii (CNCM I-1079) on feed intake, blood parameters, and production during early lactation. J Dairy Sci 2022; 106:187-201. [DOI: 10.3168/jds.2021-21740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 08/06/2022] [Indexed: 11/09/2022]
|
10
|
Qiao Z, Wang X, Wang C, Han J, Qi W, Zhang H, Liu Z, You C. Lactobacillus paracasei BD5115-Derived 2-Hydroxy-3-Methylbutyric Acid Promotes Intestinal Epithelial Cells Proliferation by Upregulating the MYC Signaling Pathway. Front Nutr 2022; 9:799053. [PMID: 35369066 PMCID: PMC8968858 DOI: 10.3389/fnut.2022.799053] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 02/08/2022] [Indexed: 01/22/2023] Open
Abstract
Metabolites of probiotics that are beneficial to human health have been isolated from the intestinal tract and natural dairy products. However, many studies on probiotics and prebiotics are limited to the observation of human cohorts and animal phenotypes. The molecular mechanisms by which metabolites of probiotics regulate health are still need further exploration. In this work, we isolated a strain of Lactobacillus Paracasei from human milk samples. We numbered it as Lactobacillus Paracasei BD5115. The mouse model of high-fat diet confirmed that the metabolites of this strain also promotes intestinal epithelial cells (IECs) proliferation. Single-cell sequencing showed that a bZIP transcription factor MAFF was specifically expressed in some IECs. We found that MAFF interacted with MBP1 to regulate the expression of MYC. Analysis of the active components in BD5115 metabolites confirmed that 2-hydroxy-3-methylbutyric acid promotes the expression of the MYC gene. This promotes the proliferation of IECs. Our findings indicate that 2-hydroxy-3-methylbutyric acid regulate MYC gene expression mediated by MAFF/MBP1 interaction. This study not only screened a strain with promoted IECs proliferation, but also discovered a new signal pathway that regulates MYC gene expression.
Collapse
Affiliation(s)
- Zhenyi Qiao
- State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, China
- State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Postdoctoral Workstation of Bright Dairy–Shanghai Jiao Tong University, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, China
| | - Xiaohua Wang
- State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, China
| | - Chaoyue Wang
- State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, China
- College of Food Science and Technology, Shanghai Ocean University, Shanghai, China
| | - Jin Han
- State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, China
| | - Weiwei Qi
- Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai, China
| | - Huanchang Zhang
- State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, China
| | - Zhenmin Liu
- State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, China
| | - Chunping You
- State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, China
- *Correspondence: Chunping You
| |
Collapse
|
11
|
Xue Y, Zhu MJ. Unraveling enterohemorrhagic Escherichia coli infection: the promising role of dietary compounds and probiotics in bacterial elimination and host innate immunity boosting. Crit Rev Food Sci Nutr 2021; 63:1551-1563. [PMID: 34404306 DOI: 10.1080/10408398.2021.1965538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
The innate immune system has developed sophisticated strategies to defense against infections. Host cells utilize the recognition machineries such as toll-like receptors and nucleotide binding and oligomerization domain-like receptors to identify the pathogens and alert immune system. However, some pathogens have developed tactics to evade host defenses, including manipulation of host inflammatory response, interference with cell death pathway, and highjack of phagocytosis signaling for a better survival and colonization in host. Enterohemorrhagic Escherichia coli (EHEC) is a notorious foodborne pathogen that causes severe tissue damages and gastrointestinal diseases, which has been reported to disturb host immune responses. Diverse bioactive compounds such as flavonoids, phenolic acids, alkaloids, saccharides, and terpenoids derived from food varieties and probiotics have been discovered and investigated for their capability of combating bacterial infections. Some of them serve as novel antimicrobial agents and act as immune boosters that harness host immune system. In this review, we will discuss how EHEC, specifically E. coli O157:H7, hijacks the host immune system and interferes with host signaling pathway; and highlight the promising role of food-derived bioactive compounds and probiotics in harnessing host innate immunity and eliminating E. coli O157:H7 infection with multiple strategies.
Collapse
Affiliation(s)
- Yansong Xue
- Key Laboratory of Functional Dairy, Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Mei-Jun Zhu
- School of Food Science, Washington State University, Pullman, WA, USA
| |
Collapse
|
12
|
Simon E, Călinoiu LF, Mitrea L, Vodnar DC. Probiotics, Prebiotics, and Synbiotics: Implications and Beneficial Effects against Irritable Bowel Syndrome. Nutrients 2021; 13:nu13062112. [PMID: 34203002 PMCID: PMC8233736 DOI: 10.3390/nu13062112] [Citation(s) in RCA: 106] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 06/05/2021] [Accepted: 06/16/2021] [Indexed: 12/12/2022] Open
Abstract
Irritable bowel syndrome (IBS) is still a common functional gastrointestinal disease that presents chronic abdominal symptoms but with a pathophysiology that is not yet fully elucidated. Moreover, the use of the synergistic combination of prebiotics and probiotics, known as synbiotics, for IBS therapy is still in the early stages. Advancements in technology led to determining the important role played by probiotics in IBS, whereas the present paper focuses on the detailed review of the various pathophysiologic mechanisms of action of probiotics, prebiotics, and synbiotics via multidisciplinary domains involving the gastroenterology (microbiota modulation, alteration of gut barrier function, visceral hypersensitivity, and gastrointestinal dysmotility) immunology (intestinal immunological modulation), and neurology (microbiota–gut–brain axis communication and co-morbidities) in mitigating the symptoms of IBS. In addition, this review synthesizes literature about the mechanisms involved in the beneficial effects of prebiotics and synbiotics for patients with IBS, discussing clinical studies testing the efficiency and outcomes of synbiotics used as therapy for IBS.
Collapse
Affiliation(s)
- Elemer Simon
- Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania; (E.S.); (L.F.C.)
| | - Lavinia Florina Călinoiu
- Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania; (E.S.); (L.F.C.)
- Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania;
| | - Laura Mitrea
- Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania;
| | - Dan Cristian Vodnar
- Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania; (E.S.); (L.F.C.)
- Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania;
- Correspondence: ; Tel.: +40-747-341-881
| |
Collapse
|
13
|
Yeni F, Samut H, Soyer Y. Effect of Non-LAB Probiotics on Foodborne Enteric Pathogens: A Systematic Review. FOOD REVIEWS INTERNATIONAL 2021. [DOI: 10.1080/87559129.2021.1938114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Affiliation(s)
- Filiz Yeni
- Department of Food Engineering, Middle East Technical University, Ankara, Turkey
| | - Hilal Samut
- Department of Food Engineering, Middle East Technical University, Ankara, Turkey
| | - Yeşim Soyer
- Department of Food Engineering, Middle East Technical University, Ankara, Turkey
| |
Collapse
|
14
|
Constante M, De Palma G, Lu J, Jury J, Rondeau L, Caminero A, Collins SM, Verdu EF, Bercik P. Saccharomyces boulardii CNCM I-745 modulates the microbiota-gut-brain axis in a humanized mouse model of Irritable Bowel Syndrome. Neurogastroenterol Motil 2021; 33:e13985. [PMID: 32955166 DOI: 10.1111/nmo.13985] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 08/12/2020] [Accepted: 08/17/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Gnotobiotic mice colonized with microbiota from patients with irritable bowel syndrome (IBS) and comorbid anxiety (IBS+A) display gut dysfunction and anxiety-like behavior compared to mice colonized with microbiota from healthy volunteers. Using this model, we tested the therapeutic potential of the probiotic yeast Saccharomyces boulardii strain CNCM I-745 (S. bou) and investigated underlying mechanisms. METHODS Germ-free Swiss Webster mice were colonized with fecal microbiota from an IBS+A patient or a healthy control (HC). Three weeks later, mice were gavaged daily with S. boulardii or placebo for two weeks. Anxiety-like behavior (light preference and step-down tests), gastrointestinal transit, and permeability were assessed. After sacrifice, samples were taken for gene expression by NanoString and qRT-PCR, microbiota 16S rRNA profiling, and indole quantification. KEY RESULTS Mice colonized with IBS+A microbiota developed faster gastrointestinal transit and anxiety-like behavior (longer step-down latency) compared to mice with HC microbiota. S. bou administration normalized gastrointestinal transit and anxiety-like behavior in mice with IBS+A microbiota. Step-down latency correlated with colonic Trpv1 expression and was associated with altered microbiota profile and increased Indole-3-acetic acid (IAA) levels. CONCLUSIONS & INFERENCES Treatment with S. bou improves gastrointestinal motility and anxiety-like behavior in mice with IBS+A microbiota. Putative mechanisms include effects on pain pathways, direct modulation of the microbiota, and indole production by commensal bacteria.
Collapse
Affiliation(s)
- Marco Constante
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Giada De Palma
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Jun Lu
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Jennifer Jury
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Liam Rondeau
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Alberto Caminero
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Stephen M Collins
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Elena F Verdu
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Premysl Bercik
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| |
Collapse
|
15
|
Li R, Wan X, Takala TM, Saris PEJ. Heterologous Expression of the Leuconostoc Bacteriocin Leucocin C in Probiotic Yeast Saccharomyces boulardii. Probiotics Antimicrob Proteins 2021; 13:229-237. [PMID: 32567021 PMCID: PMC7904741 DOI: 10.1007/s12602-020-09676-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
The yeast Saccharomyces boulardii is well known for its probiotic effects such as treating or preventing gastrointestinal diseases. Due to its ability to survive in stomach and intestine, S. boulardii could be applied as a vehicle for producing and delivering bioactive substances of interest to human gut. In this study, we cloned the gene lecC encoding the antilisterial peptide leucocin C from lactic acid bacterium Leuconostoc carnosum in S. boulardii. The constructed S. boulardii strain secreted a peptide, which had molecular weight corresponding to leucocin C in SDS-PAGE. The peptide band inhibited Listeria monocytogenes in gel overlay assay. Likewise, concentrated S. boulardii culture supernatant inhibited the growth of L. monocytogenes. The growth profile and acid tolerance of the leucocin C secreting S. boulardii were similar as those of the strain carrying the empty vector. We further demonstrated that the cells of the leucocin C producing S. boulardii efficiently killed L. monocytogenes, also without antibiotic selection pressure. These results showed that antilisterial activity could be added to the arsenal of probiotic activities of S. boulardii, demonstrating its potential as a carrier for therapeutics delivery.
Collapse
Affiliation(s)
- Ran Li
- Department of Microbiology, Faculty of Agriculture and Forestry, University of Helsinki, Viikinkaari 9, P.O. Box 56, 00014, Helsinki, Finland.
| | - Xing Wan
- Department of Microbiology, Faculty of Agriculture and Forestry, University of Helsinki, Viikinkaari 9, P.O. Box 56, 00014, Helsinki, Finland
| | - Timo M Takala
- Department of Microbiology, Faculty of Agriculture and Forestry, University of Helsinki, Viikinkaari 9, P.O. Box 56, 00014, Helsinki, Finland
| | - Per E J Saris
- Department of Microbiology, Faculty of Agriculture and Forestry, University of Helsinki, Viikinkaari 9, P.O. Box 56, 00014, Helsinki, Finland
| |
Collapse
|
16
|
Hua Y, Wu J, Fu M, Liu J, Li X, Zhang B, Zhao W, Wan C. Enterohemorrhagic Escherichia coli Effector Protein EspF Interacts With Host Protein ANXA6 and Triggers Myosin Light Chain Kinase (MLCK)-Dependent Tight Junction Dysregulation. Front Cell Dev Biol 2020; 8:613061. [PMID: 33425920 PMCID: PMC7785878 DOI: 10.3389/fcell.2020.613061] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 12/02/2020] [Indexed: 01/06/2023] Open
Abstract
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important foodborne pathogen that can cause bloody diarrhea and hemolytic uremic syndrome (HUS) in humans. EspF is one of the best-characterized effector proteins secreted from the type three secretion system to hijack host cell functions. However, the crucial pathogen-host interactions and the basis for the intestinal barrier disruption during infections remain elusive. Our previous study screened and verified the interaction between host protein ANXA6 and EspF protein. Here, by fluorescence resonance energy transfer (FRET) and co-immunoprecipitation (CO-IP), we verified that EspF interacts with ANXA6 through its C-terminal domain. Furthermore, we found that both the constitutive expression of EspF or ANXA6 and the co-expression of EspF-ANXA6 could decrease the levels of tight junction (TJ) proteins ZO-1 and occludin, and disrupt the distribution of ZO-1. Moreover, we showed that EspF-ANXA6 activated myosin light chain kinase (MLCK), induced the phosphorylation of myosin light chain (MLC) and PKCα, and down-regulated the expression level of Calmodulin protein. Collectively, this study revealed a novel interaction between the host protein (ANXA6) and EspF. The binding of EspF to ANXA6 may perturb TJs in an MLCK-MLC-dependent manner, and thus may be involved in EHEC pathogenic function.
Collapse
Affiliation(s)
- Ying Hua
- Biosafety Level 3 Laboratory, Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, China.,Key Laboratory of Tropical Disease Research of Guangdong Province, Guangzhou, China
| | - Jiali Wu
- Biosafety Level 3 Laboratory, Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Muqing Fu
- Biosafety Level 3 Laboratory, Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Jinyue Liu
- Biosafety Level 3 Laboratory, Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Xiaoxia Li
- Biosafety Level 3 Laboratory, Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Bao Zhang
- Biosafety Level 3 Laboratory, Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, China.,Key Laboratory of Tropical Disease Research of Guangdong Province, Guangzhou, China
| | - Wei Zhao
- Biosafety Level 3 Laboratory, Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, China.,Key Laboratory of Tropical Disease Research of Guangdong Province, Guangzhou, China
| | - Chengsong Wan
- Biosafety Level 3 Laboratory, Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, China.,Key Laboratory of Tropical Disease Research of Guangdong Province, Guangzhou, China
| |
Collapse
|
17
|
Lin CY, Lee AH, Chiu KK, Vieson MD, Steelman AJ, Swanson KS. Saccharomyces cerevisiae Fermentation Product Did Not Attenuate Clinical Signs, but Psyllium Husk Has Protective Effects in a Murine Dextran Sulfate Sodium-Induced Colitis Model. Curr Dev Nutr 2020; 4:nzaa159. [PMID: 33215055 PMCID: PMC7658636 DOI: 10.1093/cdn/nzaa159] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 10/02/2020] [Accepted: 10/13/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Yeast products and psyllium husk may provide relief from clinical signs of colitis due to their ability to promote gut integrity, modulate gut microbiota, or positively affect immune responses, which have been demonstrated in several species. OBJECTIVE The objective of this study was to investigate the effects of a Saccharomyces cerevisiae fermentation product (SCFP) and psyllium husk (PH) on cecal and fecal microbiota, colonic gene expression and histopathology, and mesenteric lymph node (MLN) immune cells in a dextran sulfate sodium (DSS)-induced colitis model. METHODS Male C57BL/6J mice (n = 54) were assigned to a control, 5% SCFP, or 5% PH diet. After 2 wk of diet adaptation, mice were provided distilled water or 3% (wt:vol) DSS for 5 d ad libitum. Body weight, food and water intakes, and disease activity index (DAI) were recorded daily during the treatment period. Fresh fecal samples were collected before and during treatment for microbial analyses. After treatment, mice were killed, followed by tissue collection. Tissues were stored in proper solutions until further analyses. Data were analyzed using the Mixed Models procedure of SAS 9.4 (SAS Institute). RESULTS Consumption of SCFP increased (P < 0.05) species richness of the gut microbiota and relative abundance of Butyricicoccus in fecal and cecal samples compared with control or PH mice. PH mice had greater (P < 0.05) gene expression of claudin (Cldn) 2, Cldn3, Cldn8, and occludin(Ocln) compared with control mice. DAI, MLN immune cell populations, colonic histopathology, and colonic gene expression were not affected (P > 0.05) by SCFP in DSS mice. DSS mice consuming PH had lower (P < 0.05) DAI compared with control or SCFP mice. CONCLUSIONS Results suggest that, despite the modest changes it had on cecal and fecal microbiota, SCFP did not attenuate clinical signs associated with DSS-induced colitis in mice, while PH showed protective effects.
Collapse
Affiliation(s)
- Ching-Yen Lin
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
| | - Anne H Lee
- Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
| | - Karen K Chiu
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
- College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA
| | - Miranda D Vieson
- College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA
| | - Andrew J Steelman
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
- Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
| | - Kelly S Swanson
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
- Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
| |
Collapse
|
18
|
Yang J, Qiu Y, Hu S, Zhu C, Wang L, Wen X, Yang X, Jiang Z. Lactobacillus plantarum inhibited the inflammatory response induced by enterotoxigenic Escherichia coli K88 via modulating MAPK and NF-κB signalling in intestinal porcine epithelial cells. J Appl Microbiol 2020; 130:1684-1694. [PMID: 32870564 DOI: 10.1111/jam.14835] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 07/28/2020] [Accepted: 08/21/2020] [Indexed: 12/22/2022]
Abstract
AIMS To investigate the effects of Lactobacillus plantarum on inflammatory responses induced by ETEC K88 and explore the underlying molecular mechanisms. METHODS AND RESULTS Intestinal porcine cells (IPEC-1) were incubated with 0 or 1 × 108 CFU per well L. plantarum for 4 h, and then these cells were challenged with 0 or 1 × 108 CFU per well ETEC K88 for 2 h. The results showed that pre-treatment of IPEC-1 cells with L. plantarum prevented the increases in the transcript abundance of interleukin-1α (IL-1α), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α) (P < 0·05) caused by ETEC K88. Additionally, L. plantarum inhibited the reduction in peroxisome proliferator-activated receptor-γ (PPAR-γ) expression caused by ETEC K88 (P < 0·05). Moreover, L. plantarum pre-treatment downregulated the phosphorylation levels of c-Jun N-terminal kinase (JNK), extracellular regulated protein kinases 1 and 2 (ERK1/2) and p38 and the nuclear concentration of nuclear factor kappa B p65 (NF-κB p65) (P < 0·05) compared with ETEC K88 group. Silencing experiment further supported that the protective effect of L. plantarum P might mediated by suppression of ETEC-provoked activation of MAPK and NF-κB signalling pathways. CONCLUSIONS Lactobacillus plantarum inhibited the inflammatory response induced by ETEC K88 in IPEC-1 cells via modulating MAPK and NF-κB signalling. SIGNIFICANCE AND IMPACT OF THE STUDY This study elucidated the underlying mechanism in which probiotics protect against intestinal inflammation caused by ETEC K88.
Collapse
Affiliation(s)
- J Yang
- State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture and Rural Affairs, Guangdong Public Laboratory of Animal Breeding and Nutrition; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Y Qiu
- State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture and Rural Affairs, Guangdong Public Laboratory of Animal Breeding and Nutrition; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - S Hu
- State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture and Rural Affairs, Guangdong Public Laboratory of Animal Breeding and Nutrition; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - C Zhu
- State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture and Rural Affairs, Guangdong Public Laboratory of Animal Breeding and Nutrition; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - L Wang
- State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture and Rural Affairs, Guangdong Public Laboratory of Animal Breeding and Nutrition; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - X Wen
- State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture and Rural Affairs, Guangdong Public Laboratory of Animal Breeding and Nutrition; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - X Yang
- State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture and Rural Affairs, Guangdong Public Laboratory of Animal Breeding and Nutrition; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Z Jiang
- State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture and Rural Affairs, Guangdong Public Laboratory of Animal Breeding and Nutrition; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| |
Collapse
|
19
|
Roohvand F, Ehsani P, Abdollahpour-Alitappeh M, Shokri M, Kossari N. Biomedical applications of yeasts - a patent view, part two: era of humanized yeasts and expanded applications. Expert Opin Ther Pat 2020; 30:609-631. [PMID: 32529867 DOI: 10.1080/13543776.2020.1781816] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Yeast humanization, ranging from a simple point mutation to substitution of yeast gene(s) or even a complete pathway by human counterparts has enormously expanded yeast biomedical applications. AREAS COVERED General and patent-oriented insights into the application of native and humanized yeasts for production of human glycoproteins (gps) and antibodies (Abs), toxicity/mutagenicity assays, treatments of gastrointestinal (GI) disorders and potential drug delivery as a probiotic (with emphasis on Saccharomyces bulardii) and studies on human diseases/cancers and screening effective drugs. EXPERT OPINION Humanized yeasts cover the classical advantageous features of a 'microbial eukaryote' together with advanced human cellular processes. These unique characteristics would permit their use in the production of functional and stable therapeutic gps and Abs in lower prices compared to mammalian (CHO) production-based systems. Availability of yeasts humanized for cytochrome P450 s will expand their application in metabolism-related chemical toxicity assays. Engineered S. bulardii for expression of human proteins might expand its application by synergistically combining the probiotic activity with the treatment of metabolic diseases such as phenylketonuria via GI-delivery. Yeast models of human diseases will facilitate rapid functional/phenotypic characterization of the disease-producing mutant genes and screening of the therapeutic compounds using yeast-based high-throughput research techniques (Yeast one/two hybrid systems) and viability assays.
Collapse
Affiliation(s)
- Farzin Roohvand
- Department of Virology, Pasteur Institute of Iran , Tehran, Iran
| | - Parastoo Ehsani
- Department of Molecular Biology, Pasteur Institute of Iran , Tehran, Iran
| | | | - Mehdi Shokri
- ; Department of Dental Biomaterials, School of Dentistry, Shahid Beheshti University of Medical Sciences , Tehran, Iran
| | - Niloufar Kossari
- ; Universite de Versailles, Service de ne 'phrologie-transplantation re'nale, Hopital Foch, 40 rue Worth, Suresnes , Paris, France
| |
Collapse
|
20
|
Alassane-Kpembi I, Canlet C, Tremblay-Franco M, Jourdan F, Chalzaviel M, Pinton P, Cossalter AM, Achard C, Castex M, Combes S, Bracarense APL, Oswald IP. 1H-NMR metabolomics response to a realistic diet contamination with the mycotoxin deoxynivalenol: Effect of probiotics supplementation. Food Chem Toxicol 2020; 138:111222. [PMID: 32145353 DOI: 10.1016/j.fct.2020.111222] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 02/13/2020] [Accepted: 02/17/2020] [Indexed: 01/18/2023]
Abstract
Low-level contamination of food and feed by deoxynivalenol (DON) is unavoidable. We investigated the effects of subclinical treatment with DON, and supplementation with probiotic yeast Saccharomyces cerevisiae boulardii I1079 as a preventive strategy in piglets. Thirty-six animals were randomly assigned to either a control diet, a diet contaminated with DON (3 mg/kg), a diet supplemented with yeast (4 × 109 CFU/kg), or a DON-contaminated diet supplemented with yeast, for four weeks. Plasma and tissue samples were collected for biochemical analysis,1H-NMR untargeted metabolomics, and histology. DON induced no significant modifications in biochemical parameters. However, lesion scores were higher and metabolomics highlighted alterations of amino acid and 2-oxocarboxylic acid metabolism. Administering yeast affected aminoacyl-tRNA synthesis and amino acid and glycerophospholipid metabolism. Yeast supplementation of piglets exposed to DON prevented histological alterations, and partial least square discriminant analysis emphasised similarity between the metabolic profiles of their plasma and that of the control group. The effect on liver metabolome remained marginal, indicating that the toxicity of the mycotoxin was not eliminated. These findings show that the 1H-NMR metabolomics profile is a reliable biomarker to assess subclinical exposure to DON, and that supplementation with S. cerevisiae boulardii increases the resilience of piglets to this mycotoxin.
Collapse
Affiliation(s)
- Imourana Alassane-Kpembi
- Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France; Université D'Abomey-Calavi, Ecole Polytechnique D'Abomey, Calavi, Benin.
| | - Cecile Canlet
- Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France.
| | - Marie Tremblay-Franco
- Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France.
| | - Fabien Jourdan
- Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France.
| | | | - Philippe Pinton
- Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France.
| | - Anne Marie Cossalter
- Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France.
| | - Caroline Achard
- Lallemand SAS, 19 Rue des Briquetiers, BP 59, 31702, Blagnac Cedex, France.
| | - Mathieu Castex
- Lallemand SAS, 19 Rue des Briquetiers, BP 59, 31702, Blagnac Cedex, France.
| | - Sylvie Combes
- GenPhySE, Université de Toulouse, INRA, ENVT, Castanet Tolosan, France.
| | | | - Isabelle P Oswald
- Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France.
| |
Collapse
|
21
|
Shamekhi S, Lotfi H, Abdolalizadeh J, Bonabi E, Zarghami N. An overview of yeast probiotics as cancer biotherapeutics: possible clinical application in colorectal cancer. Clin Transl Oncol 2020; 22:1227-1239. [PMID: 31919760 DOI: 10.1007/s12094-019-02270-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2019] [Accepted: 12/08/2019] [Indexed: 02/07/2023]
Abstract
The previous reports have established a strong link between diet, lifestyle, and gut microbiota population with the onset of the colorectal cancer (CRC). Administration of probiotics has become a particular interest in prevention and treatment of CRC. As potential dietary complements, probiotics might be able to lower the risk of CRC and manage the safety of traditional cancer therapies such as surgery, radiation therapy, and chemotherapy. This review investigates the promising effects of probiotics as biotherapeutics, with due attention to possible clinical application of yeast probiotics in prevention and treatment of CRC. In addition, various underlying anti-cancer mechanisms are covered here based on scientific evidence and findings from numerous experimental studies. Application of probiotics as biotherapeutics in CRC, however, needs to be approved by human clinical trials. It is of prime concern, to find potential probiotic strains, effective doses for administrations and regimes, and molecular mechanisms involved in prevention and treatment.
Collapse
Affiliation(s)
- S Shamekhi
- Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - H Lotfi
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - J Abdolalizadeh
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - E Bonabi
- Department of Medical Microbiology, Faculty of Medicine, Istanbul Aydin University, Istanbul, Turkey
| | - N Zarghami
- Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. .,Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. .,Department of Clinical Biochemistry and Laboratory Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
| |
Collapse
|
22
|
Moens F, Duysburgh C, van den Abbeele P, Morera M, Marzorati M. Lactobacillus rhamnosus GG and Saccharomyces cerevisiae boulardii exert synergistic antipathogenic activity in vitro against enterotoxigenic Escherichia coli. Benef Microbes 2019; 10:923-935. [DOI: 10.3920/bm2019.0064] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Short-term colonic in vitro batch incubations were performed to elucidate the possible synergistic effects of Lactobacillus rhamnosus GG (CNCM-I-4798) and Saccharomyces cerevisiae boulardii (CNCM-I-1079) (associated in Smebiocta/Smectaflora Protect®) on the colonic microbial fermentation process, as well as their antipathogenic activity against enterotoxigenic Escherichia coli (LMG2092) (ETEC). These incubations adequately simulate the native microbiota and environmental conditions of the proximal colon of both adult and toddler donors, including the colonic mucosal layer. Results indicated that both strains were capable of growing together without showing antagonistic effects. Co-cultivation of both strains resulted in increased butyrate (stimulated by L. rhamnosus GG), propionate (stimulated by S. boulardii), and ethanol (produced by S. boulardii) production compared to the control incubations, revealing the additive effect of both strains. After inoculation of ETEC under simulated dysbiotic conditions, a 40 and 46% reduction in the concentration of ETEC was observed upon addition of both strains during the experiments with the adult and toddler donor, respectively. Furthermore, ETEC toxin levels decreased upon S. boulardii inoculation, probably due to proteolytic activity of this strain, with a synergistic effect being observed upon co-cultivation of L. rhamnosus GG and S. boulardii resulting in a reduction of 57 and 46% for the adult and toddler donor, respectively. Altogether, the results suggest that both probiotics together may help microbiota functionality, in both adults and toddlers and under healthy or impaired conditions, which could be of great interest when the colonic microbiota is dysbiotic and therefore sensitive to pathogenic invasion such as during antibiotic treatment.
Collapse
Affiliation(s)
- F. Moens
- ProDigest bvba, Technologiepark 82, 9052 Ghent, Belgium
| | - C. Duysburgh
- ProDigest bvba, Technologiepark 82, 9052 Ghent, Belgium
| | | | - M. Morera
- Ipsen Pharma SAS, 65 Quai George Gors, 92650 Boulogne Billancourt Cedex, France
| | - M. Marzorati
- ProDigest bvba, Technologiepark 82, 9052 Ghent, Belgium
- Center of Microbial Ecology and Technology (CMET), Ghent University, Coupure Links 653, 9000 Ghent, Belgium
| |
Collapse
|
23
|
Effect of Multi-Microbial Probiotic Formulation Bokashi on Pro- and Anti-Inflammatory Cytokines Profile in the Serum, Colostrum and Milk of Sows, and in a Culture of Polymorphonuclear Cells Isolated from Colostrum. Probiotics Antimicrob Proteins 2019; 11:220-232. [PMID: 29305686 PMCID: PMC6449489 DOI: 10.1007/s12602-017-9380-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The use of probiotics in sows during pregnancy and lactation and their impact on the quality of colostrum and milk, as well as the health conditions of their offspring during the rearing period, are currently gaining the attention of researchers. The aim of the study was to determine the effect of Bokashi formulation on the concentrations of pro- and anti-inflammatory cytokines in the serum of sows during pregnancy, in their colostrum and milk, and in a culture of Con-A-stimulated polymorphonuclear cells (PMNs) isolated from the colostrum. The study was conducted on 60 sows aged 2–4 years. EM Bokashi were added to the sows’ feed. The material for the study consisted of peripheral blood, colostrum, and milk. Blood samples were collected from the sows on days 60 and 114 of gestation. Colostrum and milk samples were collected from all sows at 0, 24, 48, 72, 96, 120, 144, and 168 h after parturition. The results indicate that the use of Bokashi as feed additives resulted in increased concentrations of pro-inflammatory cytokines TNF-α and IL-6, which increase the protective capacity of the colostrum by stimulating cellular immune mechanisms protecting the sow and neonates against infection. At the same time, the increased concentrations of cytokines IL-4, IL-10, TGF-β, and of immunoglobulins in the colostrum and milk from sows in the experimental group demonstrate the immunoregulatory effect of Bokashi on Th2 cells and may lead to increased expression of regulatory T cells and polarization of the immune response from Th1 to Th2.
Collapse
|
24
|
Justino PFC, Franco AX, Pontier-Bres R, Monteiro CES, Barbosa ALR, Souza MHLP, Czerucka D, Soares PMG. Modulation of 5-fluorouracil activation of toll-like/MyD88/NF-κB/MAPK pathway by Saccharomyces boulardii CNCM I-745 probiotic. Cytokine 2019; 125:154791. [PMID: 31401369 DOI: 10.1016/j.cyto.2019.154791] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 07/23/2019] [Accepted: 07/24/2019] [Indexed: 11/19/2022]
Abstract
BACKGROUND AND AIM Chemotherapy drugs that act via Toll-like receptors (TLRs) can exacerbate mucosal injury through the production of cytokines. Intestinal mucositis can activate TLR2 and TLR4, resulting in the activation of NF-κB. Intestinal mucositis characterized by intense inflammation is the main side effect associated with 5-fluorouracil (5-FU) treatment. Saccharomyces boulardii CNCM I-745 (S.b) is a probiotic yeast used in the treatment of gastrointestinal disorders. The main objective of the study was to evaluate the effect of S.b treatment on the Toll-like/MyD88/NF-κB/MAPK pathway activated during intestinal mucositis and in Caco-2 cells treated with 5-FU. METHODS The mice were divided into three groups: saline (control), saline + 5-FU, and 5-FU + S.b (1.6 × 1010 colony forming units/kg). After 3 days of S.b administration by gavage, the mice were euthanized and the jejunum and ileum were removed. In vitro, Caco2 cells were treated with 5-FU (1 mM) alone or in the presence of lipopolysaccharide (1 ng/ml). When indicated, cells were exposed to S.b. The jejunum/ileum samples and Caco2 cells were examined for the expression or concentration of the inflammatory components. RESULTS Treatment with S.b modulated the expressions of TLR2, TLR4, MyD88, NF-κB, ERK1/2, phospho-p38, phospho-JNK, TNF-α, IL-1β, and CXCL-1 in the jejunum/ileum and Caco2 cells following treatment with 5-FU. CONCLUSION Toll-like/MyD88/NF-κB/MAPK pathway are activated during intestinal mucositis and their modulation by S.b suggests a novel and valuable therapeutic strategy for intestinal inflammation.
Collapse
Affiliation(s)
- Priscilla F C Justino
- LEFFAG - Laboratory of Physiopharmacology Study of Gastrointestinal Tract, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Alvaro X Franco
- LEFFAG - Laboratory of Physiopharmacology Study of Gastrointestinal Tract, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil
| | | | - Carlos E S Monteiro
- LEFFAG - Laboratory of Physiopharmacology Study of Gastrointestinal Tract, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil
| | - André L R Barbosa
- LAFFEX - Laboratory of Experimental Physiopharmacology, Biotechnology and Biodiversity Center Research, Federal University of Piauí, Parnaíba, Brazil
| | - Marcellus H L P Souza
- LEFFAG - Laboratory of Physiopharmacology Study of Gastrointestinal Tract, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Dorota Czerucka
- Centre Scientifique de Monaco, 8 quai Antoine 1er, MC98000, Monaco
| | - Pedro M G Soares
- LEFFAG - Laboratory of Physiopharmacology Study of Gastrointestinal Tract, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil; Department of Morphology, Medical School, Federal University of Ceara, Rua Delmiro de Farias s/n, Rodolfo Teofilo, Fortaleza, Ceara, Brazil.
| |
Collapse
|
25
|
de Castro JAA, Guno MJVR, Perez MO. Bacillus clausii as adjunctive treatment for acute community-acquired diarrhea among Filipino children: a large-scale, multicenter, open-label study (CODDLE). TROPICAL DISEASES TRAVEL MEDICINE AND VACCINES 2019; 5:14. [PMID: 31367461 PMCID: PMC6651909 DOI: 10.1186/s40794-019-0089-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 07/04/2019] [Indexed: 11/18/2022]
Abstract
Background Diarrhea is among the main causes of pediatric mortality in the Philippines. Probiotics have been shown to be beneficial in the management of acute diarrhea. Accordingly, the aim of this population-based study was to assess the safety and effectiveness of Bacillus clausii as an adjunct to standard therapy in Filipino children with acute community-acquired diarrhea of viral origin or associated with antibiotic administration. Methods A total of 3178 patients (median age of 2 years) were enrolled in this open-label, multicenter, observational study, and were treated with one to two vials of Bacillus clausii in the following bacterial stains: O/C, SIN, N/R, and T (oral suspension of 2 billion spores per 5-mL vial) for 5 to 7 days. Diarrhea duration, number of stools per day, improvement in gastrointestinal symptoms, children’s overall acceptability of Bacillus clausii therapy, and safety and tolerability were assessed. Concomitant treatment with oral rehydration solutions (26.6%), zinc (23.9%), and antibiotics prescribed for conditions other than diarrhea (13.6%) was recorded during the study. All other probiotics and antidiarrheals were prohibited. Results Therapy with Bacillus clausii was well-tolerated, and the adverse event rate was very low (0.09%). All reported adverse events, which included vomiting, erythematous rashes and stool color change, were mild to moderate. In more than half of the per-protocol population (1535/2916; 52.6%), diarrhea was resolved within the first 3 days of treatment with Bacillus clausii. There was no significant difference (p = 0.297) in mean diarrhea duration between patients with either antibiotic-associated (3.3 ± 1.3 days) or viral diarrhea (3.4 ± 1.3 days). However, children who only received Bacillus clausii supplementation without zinc had a significantly shorter diarrhea duration (3.3 ± 1.3 days) compared to zinc-treated children (3.6 ± 1.6 days; p < 0.001). Bacillus clausii significantly reduced the mean number of stools per day, from 5.2 ± 2.0 stools at baseline to 1.2 ± 0.6 stools at study end (p < 0.001). Similarly, the proportion of patients with loose stools decreased from 81.6% at baseline to 9.2% at end of treatment period. Acceptability of Bacillus clausii therapy was high. Conclusion This study adds knowledge on the good safety profile and on the effectiveness of Bacillus clausii as an adjunct treatment for acute childhood diarrhea.
Collapse
Affiliation(s)
- Jo-Anne A de Castro
- Department of Pediatrics, De La Salle Health Sciences Institute (DLSHSI) College of Medicine, Cavite, Philippines.,2Department of Microbiology and Parasitology, Pamantasang Lungsod ng Maynila College of Medicine (PLM-CM), Manila, Philippines
| | - Mary Jean Villa-Real Guno
- Ateneo School of Medicine and Public Health (ASMPH), Don Eugenio Lopez Sr. Medical Complex, Pasig, Philippines.,Department of Pediatric Gastroenterology, Hepatology and Nutrition, The Medical City (TMC), Pasig, Philippines
| | - Marcos O Perez
- 5Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Building K607, Frankfurt am Main, 65926 Germany
| |
Collapse
|
26
|
Aghamohammadi D, Ayromlou H, Dolatkhah N, Jahanjoo F, Shakouri SK. The effects of probiotic Saccharomyces boulardii on the mental health, quality of life, fatigue, pain, and indices of inflammation and oxidative stress in patients with multiple sclerosis: study protocol for a double-blind randomized controlled clinical trial. Trials 2019; 20:379. [PMID: 31234904 PMCID: PMC6591959 DOI: 10.1186/s13063-019-3454-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 05/20/2019] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND The relationship between gut dysbiosis and inflammatory diseases including multiple sclerosis (MS) is presently recognized as an important health issue. It has been established that some bacterial probiotic strains are effective in treating MS. This study will investigate the effect of yeast probiotic Saccharomyces boulardii (SB) supplements on mental health, quality of life, fatigue, pain, and indices of inflammation and oxidative stress in MS patients. METHODS/DESIGN In this double-blind randomized controlled two-group parallel trial, 50 MS patients who meet the inclusion criteria will be recruited from outpatient settings. They will be randomly allocated to 4 months of daily placebo or the SB probiotic intervention. Blood samples will be taken from each participant at the baseline and after the intervention period to assess inflammation and oxidative stress. The primary endpoint will be the changes in their mental health evaluated by the 28-item General Health Questionnaire. The secondary endpoints include changes in: (1) quality of life, evaluated by the 36-item Short Form Questionnaire, (2) fatigue, evaluated by the Fatigue Severity Scale, (3) pain, evaluated by a visual analogue scale, and (4) serum levels of indices of inflammatory stress (high-sensitivity C-reactive protein) and oxidative stress (malondialdehyde and total antioxidant capacity). Moreover, any adverse events and side effects due to the intervention will be documented. DISCUSSION There is a need to discover safe and practical methods for managing the symptoms of MS. This trial will gather evidence on the effects of a probiotic. TRIAL REGISTRATION Iranian Clinical Trial Registry, IRCT20161022030424N1 . Registered on 9 April 2018.
Collapse
Affiliation(s)
- Dawood Aghamohammadi
- Department of Anesthesiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hormoz Ayromlou
- Neuroscience Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Neda Dolatkhah
- Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Jahanjoo
- Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyed Kazem Shakouri
- Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
27
|
Czerucka D, Rampal P. Diversity of Saccharomyces boulardii CNCM I-745 mechanisms of action against intestinal infections. World J Gastroenterol 2019; 25:2188-2203. [PMID: 31143070 PMCID: PMC6526157 DOI: 10.3748/wjg.v25.i18.2188] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 03/21/2019] [Accepted: 03/30/2019] [Indexed: 02/06/2023] Open
Abstract
The yeast Saccharomyces boulardii CNCM I-745 is one of the probiotics recommended for the prevention of antibiotic-associated diarrhea. Studies conducted in vivo and in vitro demonstrated that in the case of infectious diseases there are two potential sites of action of Saccharomyces boulardii CNCM I-745: (1) An action on enteropathogenic microorganisms (adhesion of bacteria and their elimination or an effect on their virulence factors: Toxins, lipopolysaccharide, etc.); and (2) a direct action on the intestinal mucosa (trophic effects, effects on epithelial reconstitution, anti-secretory effects, anti-inflammatory, immunomodulators). Oral administration of Saccharomyces boulardii CNCM I-745 to healthy subjects does not alter their microbiota. However, in the case of diseases associated with the use of antibiotics or chronic diarrhea, Saccharomyces boulardii CNCM I-745 can restore the intestinal microbiota faster. The interaction of Saccharomyces boulardii CNCM I-745 with the innate immune system have been recently demonstrated thus opening up a new therapeutic potential of this yeast in the case of diseases associated with intestinal infections but also other pathologies associated with dysbiosis such as inflammatory diseases.
Collapse
Affiliation(s)
- Dorota Czerucka
- Department of Human Health, Division of Ecosystems and Immunity, Center Scientific of Monaco, Monaco MC98000, Monaco
| | | |
Collapse
|
28
|
Terciolo C, Dapoigny M, Andre F. Beneficial effects of Saccharomyces boulardii CNCM I-745 on clinical disorders associated with intestinal barrier disruption. Clin Exp Gastroenterol 2019; 12:67-82. [PMID: 30804678 PMCID: PMC6375115 DOI: 10.2147/ceg.s181590] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Intestinal barrier defects lead to "leaky gut syndrome", defined as an increase in intestinal permeability that allows the passage of luminal content into intestinal tissue and the bloodstream. Such a compromised intestinal barrier is the main factor underlying the pathogenesis of inflammatory bowel disease, but also commonly occurs in various systemic diseases such as viral infections and metabolic syndrome. The non-pathogenic yeast Saccharomyces boulardii CNCM I-745 has demonstrated its effectiveness as a probiotic in the prevention and treatment of antibiotic-associated, infectious and functional diarrhea. Via multiple mechanisms of action implicated in intestinal barrier function, S. boulardii has beneficial effects on altered intestinal microbiota and epithelial barrier defects in different pathologies. The well-studied probiotic yeast S. boulardii plays a crucial role in the preservation and/or restoration of intestinal barrier function in multiple disorders. This could be of major interest in diseases characterized by alterations in intestinal barrier function.
Collapse
Affiliation(s)
- Chloe Terciolo
- INRA, UMR 1331 Toxalim, Research Center in Food Toxicology, F-31027 Toulouse, France,
- Aix-Marseille Université, INSERM, UMR 911, CRO2, Marseille, France,
| | - Michel Dapoigny
- Médecine Digestive, CHU Estaing, CHU Clermont-Ferrand, Université Clermont Auvergne, INSERM UMR 1107, Neuro-Dol, Clermont-Ferrand, France
| | - Frederic Andre
- Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc scientifique et technologique de Luminy, Marseille, France
| |
Collapse
|
29
|
Senkarcinova B, Graça Dias IA, Nespor J, Branyik T. Probiotic alcohol-free beer made with Saccharomyces cerevisiae var. boulardii. Lebensm Wiss Technol 2019. [DOI: 10.1016/j.lwt.2018.10.082] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
|
30
|
Ribeiro M, Oliveira D, Oliveira F, Caliari M, Martins F, Nicoli J, Torres M, Andrade M, Cardoso V, Gomes M. Effect of probiotic Saccharomyces boulardii in experimental giardiasis. Benef Microbes 2018; 9:789-797. [DOI: 10.3920/bm2017.0155] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The aim of the study was to assess the efficacy of Saccharomyces boulardii in experimental treatment of giardiasis and its impact on intestinal integrity and some functions of gerbils infected with Giardia lamblia. 28 gerbils (Meriones unguiculatus), aged 4-6 weeks, were divided into four groups: untreated and uninfected control (CT); infected with G. lamblia (IGL); treated with S. boulardii (SB); and infected with G. lamblia and treated with S. boulardii (ITSB). The SB and ITSB groups received S. boulardii 15 days prior to being infected with G. lamblia. The treatment continued until completion of the experiment (22nd day). The IGL and ITSB groups were gavage-inoculated with G. lamblia ensuring one-week infection. 4 h before euthanasia, all animals were gavaged with a solution containing diethylenetriamine-pentaacetic acid (DTPA) marked with technetium-99mTc DTPA to determine intestinal permeability. The small intestine was removed for histopathological, morphometric analysis and count of trophozoites adhered to the mucosa. The selected probiotic caused an approximate reduction of 70% of parasite load, which was determined by attached trophozoites (P<0.01) and immune-marked trophozoites (P<0.05). Treatment with S. boulardii (SB and ITSB groups) also increased the height of the intestinal villi and crypt depth compared to the CT and IGL groups (P<0.05). The area of mucus production and the number of goblet cells of the SB and ITSB groups were higher compared to the CT and IGL groups (P<0.01). The animals treated with S. boulardii also exhibited a significant increase of intraepithelial lymphocytes counts (P<0.01). There was no difference in the intestinal permeability between the groups studied. The efficacy of S. boulardii in reducing damages caused by Giardia was demonstrated, with an approximate reduction of 70% of the parasite load, suggesting its use as a coadjuvant in giardiasis treatment.
Collapse
Affiliation(s)
- M.R.S. Ribeiro
- Department of Parasitology, Federal University of Minas Gerais, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, 31270-901 MG, Brazil
- Department of Basic Life Sciences, Federal University of Juiz de Fora, Campus Governador Valadares, 35010-180 MG, Brazil
| | - D.R. Oliveira
- Department of Basic Life Sciences, Federal University of Juiz de Fora, Campus Governador Valadares, 35010-180 MG, Brazil
| | - F.M.S. Oliveira
- Department of Pathology, Federal University of Minas Gerais, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, 31270-901 MG, Brazil
| | - M.V. Caliari
- Department of Pathology, Federal University of Minas Gerais, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, 31270-901 MG, Brazil
| | - F.S. Martins
- Department of Microbiology, Federal University of Minas Gerais, Pampulha, Rua Tiradentes 151, Centro, Belo Horizonte, 31970-201 MG, Brazil
| | - J.R. Nicoli
- Department of Microbiology, Federal University of Minas Gerais, Pampulha, Rua Tiradentes 151, Centro, Belo Horizonte, 31970-201 MG, Brazil
| | - M.F. Torres
- Department of Pediatrics, Federal University of Minas Gerais, Belo Horizonte, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, 31270-901 MG, Brazil
| | - M.E.R. Andrade
- Department of Clinical and Toxicological Analysis, Federal University of Minas Gerais, Belo Horizonte, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, 31270-901 MG, Brazil
| | - V.N. Cardoso
- Department of Clinical and Toxicological Analysis, Federal University of Minas Gerais, Belo Horizonte, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, 31270-901 MG, Brazil
| | - M.A. Gomes
- Department of Parasitology, Federal University of Minas Gerais, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, 31270-901 MG, Brazil
| |
Collapse
|
31
|
Zommiti M, Almohammed H, Ferchichi M. Purification and Characterization of a Novel Anti-Campylobacter Bacteriocin Produced by Lactobacillus curvatus DN317. Probiotics Antimicrob Proteins 2018; 8:191-201. [PMID: 27812926 DOI: 10.1007/s12602-016-9237-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The lactic acid bacteria (LAB) microbiota of Saudi chicken ceca was determined. From 60 samples, 204 isolates of lactic acid bacteria were obtained. Three isolates produced antimicrobial activities against Campylobacter jejuni, Listeria monocytogenes, and Bacillus subtilis. The isolate DN317, which had the highest activity against Campylobacter jejuni ATCC 33560, was identified as Lactobacillus curvatus (GenBank accession numbers: KX353849 and KX353850). Full inhibitory activity was observed after a 2-h incubation with the supernatant at pH values between 4 and 8. Only 16% of the activity was conserved after a treatment at 121 °C for 15 min. The use of proteinase K, pepsin, chymotrypsin, trypsin, papain, and lysozyme drastically reduced the antimicrobial activity. However, lipase, catalase, and lysozyme had no effect on this activity. The active peptide produced by Lactobacillus curvatus DN317 was purified by precipitation with an 80% saturated ammonium sulfate solution, and two steps of reversed phase HPLC on a C18 column. The molecular weight of this peptide was 4448 Da as determined by MALDI-ToF. N-terminal sequence analysis using Edman degradation revealed 47 amino acid residues (UniProt Knowledgebase accession number C0HK82) revealing homology with the amino acid sequences of sakacin P and curvaticin L442. The antimicrobial activity of the bacteriocin, namely curvaticin DN317, was found to be bacteriostatic against Campylobacter jejuni ATCC 33560. The use of microbial antagonism by LAB is one of the best ways to control microorganisms safely in foods. This result constitutes a reasonable advance in the antimicrobial field because of its potential applications in food technology.
Collapse
Affiliation(s)
- Mohamed Zommiti
- Unité de Protéomique Fonctionnelle et Potentiel Nutraceutique de la Biodiversité de Tunisie, Institut Supérieur des Sciences Biologiques Appliquées de Tunis, Rue Z. Essafi, 1006, Tunis, Tunisia
| | - Hamdan Almohammed
- Department of Medical Microbiology and Parasitology, College of Medicine, King Faisal University, P.O. Box: 400, Al-Ahsa, 31982, Saudi Arabia
| | - Mounir Ferchichi
- Unité de Protéomique Fonctionnelle et Potentiel Nutraceutique de la Biodiversité de Tunisie, Institut Supérieur des Sciences Biologiques Appliquées de Tunis, Rue Z. Essafi, 1006, Tunis, Tunisia.
- College of Applied Medical Sciences, Clinical Laboratory Department, King Faisal University, P.O. Box: 401, Al-Ahsa, 31982, Saudi Arabia.
| |
Collapse
|
32
|
Sharif MR, Kashani HH, Ardakani AT, Kheirkhah D, Tabatabaei F, Sharif A. The Effect of a Yeast Probiotic on Acute Diarrhea in Children. Probiotics Antimicrob Proteins 2018; 8:211-214. [PMID: 27530282 DOI: 10.1007/s12602-016-9221-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
A probiotic is a living micro-organism administered to promote the health of the host by treating or preventing infections owing to strains of pathogens. Saccharomyces boulardii is a nonpathogen yeast that has a direct inhibitory effect on the growth of many pathogens, an anti-secretory effect and a trophic effect on enterocytes. The aim of this study was to determine the effect of S. boulardii on diarrhea in children. The children from 6 months to 6 years of age with acute watery diarrhea admitted in pediatric clinic in Kashan in 2012 were included in this trial. Exclusion criteria were high fever (T > 38.5 °C), severe dehydration, bloody diarrhea, severe malnutrition, using of antibiotics, anti-diarrheal or antifungal drugs and children with more than one complain. Two hundred patients were assigned into two groups: A total of 100 patients were treated with S. boulardii in addition to ORS (case group) and 100 patients were given placebo in addition to ORS (control group). The duration of diarrhea and frequency of stools were recorded by asking the mothers of the children every day. The results showed that the defecation frequency after second day of treatment in the case group was significantly less than the control group (P = 0.001) and the mean numbers of days of diarrhea was significantly lower in the case group (P = 0.001). The result of this study confirms that S. boulardii reduces the frequency of stool and duration of illness in children.
Collapse
Affiliation(s)
- Mohammad Reza Sharif
- Infectious Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamed Haddad Kashani
- Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran
| | - Abbas Taghavi Ardakani
- Infectious Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran
| | - Davood Kheirkhah
- Infectious Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran
| | - Fatemeh Tabatabaei
- Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Alireza Sharif
- Infectious Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran.
| |
Collapse
|
33
|
Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies. Clin Microbiol Rev 2017; 30:191-231. [PMID: 27856521 DOI: 10.1128/cmr.00049-16] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Beneficial microorganisms hold promise for the treatment of numerous gastrointestinal diseases. The transfer of whole microbiota via fecal transplantation has already been shown to ameliorate the severity of diseases such as Clostridium difficile infection, inflammatory bowel disease, and others. However, the exact mechanisms of fecal microbiota transplant efficacy and the particular strains conferring this benefit are still unclear. Rationally designed combinations of microbial preparations may enable more efficient and effective treatment approaches tailored to particular diseases. Here we use an infectious disease, C. difficile infection, and an inflammatory disorder, the inflammatory bowel disease ulcerative colitis, as examples to facilitate the discussion of how microbial therapy might be rationally designed for specific gastrointestinal diseases. Fecal microbiota transplantation has already shown some efficacy in the treatment of both these disorders; detailed comparisons of studies evaluating commensal and probiotic organisms in the context of these disparate gastrointestinal diseases may shed light on potential protective mechanisms and elucidate how future microbial therapies can be tailored to particular diseases.
Collapse
|
34
|
Abstract
BACKGROUND The impact of the intestinal microbiome is increasing steadily with regard to the immune function und the defense against pathogens. The medicinal yeast Saccharomyces boulardii CNCM I-745 (S. boulardii) has been used as probiotic for the prevention and treatment of infectious diarrhea since more than 50 years. Meta-analyses confirm the clinical efficacy of S. boulardii to treat diarrhea of various origins in children and adults. METHOD This review article summarizes experimental studies on molecular and immunological mechanisms which explain the proven clinical efficacy of S. boulardii. Thereby the focus is on the gut-associated immune system. RESULTS S. boulardii stimulates the release of immunoglobulins and cytokines and also induces the maturation of immune cells. This suggests that S. boulardii is capable of activating the unspecific immune system. In case of an infection, S. boulardii is able to bind pathogenic bacteria and to neutralize their toxins. Moreover, the medicinal yeast can attenuate the overreacting inflammatory immune response, by interfering with the signaling cascade, which is induced by the infection, and that way influences the innate and adaptive immune system. Thanks to these mechanisms the pathogens' potential of adhesion is lessened. Thus the intestinal epithelial layer is protected and diarrhea-induced fluid loss is reduced. CONCLUSION The different molecular and immunological mechanisms investigated in the experimental studies prove the already confirmed very good clinical efficacy of S. boulardii in infectious diarrhea caused by pathogens such as bacteria, viruses, and fungi.
Collapse
Affiliation(s)
- Heike Stier
- analyze & realize GmbH, Waldseeweg 6, 13467, Berlin, Deutschland.
| | - Stephan C Bischoff
- Institut für Ernährungsmedizin, Universität Hohenheim, Stuttgart, Deutschland
| |
Collapse
|
35
|
Khatri I, Tomar R, Ganesan K, Prasad GS, Subramanian S. Complete genome sequence and comparative genomics of the probiotic yeast Saccharomyces boulardii. Sci Rep 2017; 7:371. [PMID: 28336969 PMCID: PMC5428479 DOI: 10.1038/s41598-017-00414-2] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Accepted: 02/23/2017] [Indexed: 02/06/2023] Open
Abstract
The probiotic yeast, Saccharomyces boulardii (Sb) is known to be effective against many gastrointestinal disorders and antibiotic-associated diarrhea. To understand molecular basis of probiotic-properties ascribed to Sb we determined the complete genomes of two strains of Sb i.e. Biocodex and unique28 and the draft genomes for three other Sb strains that are marketed as probiotics in India. We compared these genomes with 145 strains of S. cerevisiae (Sc) to understand genome-level similarities and differences between these yeasts. A distinctive feature of Sb from other Sc is absence of Ty elements Ty1, Ty3, Ty4 and associated LTR. However, we could identify complete Ty2 and Ty5 elements in Sb. The genes for hexose transporters HXT11 and HXT9, and asparagine-utilization are absent in all Sb strains. We find differences in repeat periods and copy numbers of repeats in flocculin genes that are likely related to the differential adhesion of Sb as compared to Sc. Core-proteome based taxonomy places Sb strains along with wine strains of Sc. We find the introgression of five genes from Z. bailii into the chromosome IV of Sb and wine strains of Sc. Intriguingly, genes involved in conferring known probiotic properties to Sb are conserved in most Sc strains.
Collapse
Affiliation(s)
- Indu Khatri
- CSIR-Institute of Microbial Technology, Chandigarh, India
| | - Rajul Tomar
- CSIR-Institute of Microbial Technology, Chandigarh, India
| | - K Ganesan
- CSIR-Institute of Microbial Technology, Chandigarh, India
| | - G S Prasad
- CSIR-Institute of Microbial Technology, Chandigarh, India
| | | |
Collapse
|
36
|
Cordonnier C, Thévenot J, Etienne-Mesmin L, Alric M, Livrelli V, Blanquet-Diot S. Probiotic and enterohemorrhagic Escherichia coli: An effective strategy against a deadly enemy? Crit Rev Microbiol 2016; 43:116-132. [PMID: 27798976 DOI: 10.1080/1040841x.2016.1185602] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Enterohemorrhagic Escherichia coli (EHEC) are major food-borne pathogens that constitute a serious public health threat. Currently, there is no specific treatment available for EHEC infections in human creating an urgent need for the development of alternative therapeutic strategies. Among them, one of the most promising approaches is the use of probiotic microorganisms. Even if many studies have shown the antagonistic effects of probiotic bacteria or yeast on EHEC survival, virulence, adhesion on intestinal epithelium or pathogen-induced inflammatory responses, mechanisms mediating their beneficial effects remain unclear. This review describes EHEC pathogenesis and novel therapeutic strategies, with a particular emphasis on probiotics. The interests and limits of a probiotic-based approach and the way it might be incorporated into global health strategies against EHEC infections will be discussed.
Collapse
Affiliation(s)
- Charlotte Cordonnier
- a EA 4678 CIDAM, "Conception, Ingénierie et Développement de l'Aliment et du Médicament", Centre de Recherche en Nutrition Humaine Auvergne , Université d'Auvergne , Clermont-Ferrand , France.,b M2iSH, "Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte" , UMR Inserm/Université d'Auvergne U1071, USC-INRA 2018, Centre de Recherche en Nutrition Humaine Auvergne, Université d'Auvergne , Clermont-Ferrand , France
| | - Jonathan Thévenot
- a EA 4678 CIDAM, "Conception, Ingénierie et Développement de l'Aliment et du Médicament", Centre de Recherche en Nutrition Humaine Auvergne , Université d'Auvergne , Clermont-Ferrand , France.,b M2iSH, "Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte" , UMR Inserm/Université d'Auvergne U1071, USC-INRA 2018, Centre de Recherche en Nutrition Humaine Auvergne, Université d'Auvergne , Clermont-Ferrand , France
| | - Lucie Etienne-Mesmin
- a EA 4678 CIDAM, "Conception, Ingénierie et Développement de l'Aliment et du Médicament", Centre de Recherche en Nutrition Humaine Auvergne , Université d'Auvergne , Clermont-Ferrand , France.,b M2iSH, "Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte" , UMR Inserm/Université d'Auvergne U1071, USC-INRA 2018, Centre de Recherche en Nutrition Humaine Auvergne, Université d'Auvergne , Clermont-Ferrand , France
| | - Monique Alric
- a EA 4678 CIDAM, "Conception, Ingénierie et Développement de l'Aliment et du Médicament", Centre de Recherche en Nutrition Humaine Auvergne , Université d'Auvergne , Clermont-Ferrand , France
| | - Valérie Livrelli
- b M2iSH, "Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte" , UMR Inserm/Université d'Auvergne U1071, USC-INRA 2018, Centre de Recherche en Nutrition Humaine Auvergne, Université d'Auvergne , Clermont-Ferrand , France.,c Service de Bactériologie , CHU Clermont-Ferrand , Clermont-Ferrand , France
| | - Stéphanie Blanquet-Diot
- a EA 4678 CIDAM, "Conception, Ingénierie et Développement de l'Aliment et du Médicament", Centre de Recherche en Nutrition Humaine Auvergne , Université d'Auvergne , Clermont-Ferrand , France
| |
Collapse
|
37
|
Jin Y, Blikslager AT. Myosin light chain kinase mediates intestinal barrier dysfunction via occludin endocytosis during anoxia/reoxygenation injury. Am J Physiol Cell Physiol 2016; 311:C996-C1004. [PMID: 27760753 DOI: 10.1152/ajpcell.00113.2016] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Accepted: 10/13/2016] [Indexed: 01/13/2023]
Abstract
Intestinal anoxia/reoxygenation (A/R) injury induces loss of barrier function followed by epithelial repair. Myosin light chain kinase (MLCK) has been shown to alter barrier function via regulation of interepithelial tight junctions, but has not been studied in intestinal A/R injury. We hypothesized that A/R injury would disrupt tight junction barrier function via MLCK activation and myosin light chain (MLC) phosphorylation. Caco-2BBe1 monolayers were subjected to anoxia for 2 h followed by reoxygenation in 21% O2, after which barrier function was determined by measuring transepithelial electrical resistance (TER) and FITC-dextran flux. Tight junction proteins and MLCK signaling were assessed by Western blotting, real-time PCR, or immunofluorescence microscopy. The role of MLCK was further investigated with select inhibitors (ML-7 and peptide 18) by using in vitro and ex vivo models. Following A/R injury, there was a significant increase in paracellular permeability compared with control cells, as determined by TER and dextran fluxes (P < 0.05). The tight junction protein occludin was internalized during A/R injury and relocalized to the region of the tight junction after 4 h of recovery. MLC phosphorylation was significantly increased by A/R injury (P < 0.05), and treatment with the MLCK inhibitor peptide 18 attenuated the increased epithelial monolayer permeability and occludin endocytosis caused by A/R injury. Application of MLCK inhibitors to ischemia-injured porcine ileal mucosa induced significant increases in TER and reduced mucosal-to-serosal fluxes of 3H-labeled mannitol. These data suggest that MLCK-induced occludin endocytosis mediates intestinal epithelial barrier dysfunction during A/R injury. Our results also indicate that MLCK-dependent occludin regulation may be a target for the therapeutic treatment of ischemia/reperfusion injury.
Collapse
Affiliation(s)
- Younggeon Jin
- Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina
| | - Anthony T Blikslager
- Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina
| |
Collapse
|
38
|
Al-Jashaami LS, DuPont HL. Management of Clostridium difficile Infection. Gastroenterol Hepatol (N Y) 2016; 12:609-616. [PMID: 27917075 PMCID: PMC5114503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Since the discovery of Clostridium difficile infection (CDI) in the 1970s, there has been an increase in the incidence, severity, and recurrence rate of the disease. We reviewed the recent CDI literature in PubMed published before February 28, 2016 that focused on advances in therapy. Despite a large number of studies describing methods for diagnosing the disease, there is currently no definitive test that identifies this infection with certainty, which complicates therapy. Recommended therapy for CDI includes oral metronidazole for mild cases and oral vancomycin or fidaxomicin for moderate to severe cases, each given for 10 to 14 days. For infection with spore-forming C difficile, this length of treatment may be insufficient to lead to cure; however, continuing antibiotics for longer periods of time may unfavorably alter the microbiome, preventing recovery. Treatment with metronidazole has been associated with an increasing failure rate, and the only clear recommended form of metronidazole for treatment of CDI is the intravenous formulation for patients unable to take oral medications. For vancomycin or fidaxomicin treatment of first CDI recurrences, the drug used in the initial bout can be repeated. For second or future recurrences, vancomycin can be given in pulsed or tapered doses. New modalities of treatment, such as bacteriotherapy and immunotherapy, show promise for the treatment of recurrent CDI.
Collapse
Affiliation(s)
- Layth S Al-Jashaami
- Dr Al-Jashaami is a clinical assistant professor at the University of Arizona College of Medicine in Phoenix, Arizona. Dr DuPont is a professor and director of the Center for Infectious Diseases at the University of Texas Houston School of Public Health and the McGovern Medical School in Houston, Texas; president of the Kelsey Research Foundation in Houston, Texas; and a clinical professor at Baylor College of Medicine in Houston, Texas
| | - Herbert L DuPont
- Dr Al-Jashaami is a clinical assistant professor at the University of Arizona College of Medicine in Phoenix, Arizona. Dr DuPont is a professor and director of the Center for Infectious Diseases at the University of Texas Houston School of Public Health and the McGovern Medical School in Houston, Texas; president of the Kelsey Research Foundation in Houston, Texas; and a clinical professor at Baylor College of Medicine in Houston, Texas
| |
Collapse
|
39
|
Stier H, Bischoff SC. Influence of Saccharomyces boulardii CNCM I-745on the gut-associated immune system. Clin Exp Gastroenterol 2016; 9:269-279. [PMID: 27695355 PMCID: PMC5027949 DOI: 10.2147/ceg.s111003] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background The probiotic Saccharomyces boulardii CNCM I-745 (also known as Saccharomyces cerevisiae HANSEN CBS 5926; in the following S. boulardii) has proven its effectiveness in preventive and therapeutic treatment of many gastrointestinal diseases, especially diseases associated with acute diarrhea. In particular, antibiotic-associated diarrhea, Clostridium difficile-associated diarrhea, traveller’s diarrhea, as well as acute diarrhea due to common viral and bacterial infections in children and adults. Aim The aim of this review is to summarize the experimental studies elucidating the molecular and immunological mechanisms by which these clinically proven effects are archived, with an emphasis on the gut-associated immune system. The main focus is laid on anti-inflammatory and immune-modulatory action of S. boulardii involved in bacterial or enterotoxin-mediated diarrhea and inflammation. An attempt is made to differentiate between the effects associated with cellular versus soluble factors and between prophylactic and therapeutic effects. Methods A literature search was performed in PubMed/PubMed Central for the effects of S. boulardii on the gut-associated immune system (focus acute diarrhea). Results and conclusion S. boulardii exhibits its positive effect by the direct effects on pathogens or their toxins as well as by influencing the host’s infection-induced signaling cascades and its innate and adaptive immune system. The combination of these mechanisms results in a reduction of the pathogens’ ability for adhesion or colonization and an attenuation of the overreacting inflammatory immune response. Thereby, the integrity of the intestinal epithelial cell layer is preserved or restored, and the diarrheic leakage of fluids into the intestinal lumen is attenuated.
Collapse
Affiliation(s)
| | - Stephan C Bischoff
- Department of Clinical Nutrition, University of Hohenheim, Stuttgart, Germany
| |
Collapse
|
40
|
Saber A, Alipour B, Faghfoori Z, Yari Khosroushahi A. Cellular and molecular effects of yeast probiotics on cancer. Crit Rev Microbiol 2016; 43:96-115. [PMID: 27561003 DOI: 10.1080/1040841x.2016.1179622] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The cancer is one of the main causes of human deaths worldwide. The exact mechanisms of initiation and progression of malignancies are not clear yet, but there is a common agreement about the role of colonic microbiota in the etiology of different cancers. Probiotics have been examined for their anti-cancer effects, and different mechanisms have been suggested about their antitumor functions. Nonpathogenic yeasts, as members of probiotics family, can be effective on gut microbiota dysbiosis. Generally safe yeasts have shown so many beneficial effects on human health. Probiotic yeasts influence physiology, metabolism, and immune homeostasis in the colon and contribute to cancer treatment due to possessing anti-inflammatory, anti-proliferative and anti-cancer properties. This study reviews some of the health-beneficial effects of probiotic yeasts and their biological substances like folic acid and β-glucan on cancer and focuses on the possible cellular and molecular mechanisms of probiotic yeasts such as influencing pathogenic bacteria, inactivation of carcinogenic compounds, especially those derived from food, improvement of intestinal barrier function, modulation of immune responses, antitoxic function, apoptosis, and anti-proliferative effects.
Collapse
Affiliation(s)
- Amir Saber
- a Biotechnology Research Center, Faculty of Nutrition, Tabriz University of Medical Sciences , Tabriz , Iran.,b Student Research Committee, Faculty of Nutrition, Tabriz University of Medical Sciences , Tabriz , Iran.,c Department of Biochemistry and Diet Therapy , Faculty of Nutrition, Tabriz University of Medical Sciences , Tabriz , Iran
| | - Beitollah Alipour
- c Department of Biochemistry and Diet Therapy , Faculty of Nutrition, Tabriz University of Medical Sciences , Tabriz , Iran.,d Nutrition Research Center, Faculty of Nutrition, Tabriz University of Medical Sciences , Tabriz , Iran
| | - Zeinab Faghfoori
- e Faculty of Medicine, Semnan University of Medical Sciences , Semnan , Iran
| | - Ahmad Yari Khosroushahi
- f Drug Applied Research Center, Faculty of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran.,g Department of Pharmacognosy , Faculty of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran
| |
Collapse
|
41
|
Thévenot J, Cordonnier C, Rougeron A, Le Goff O, Nguyen HTT, Denis S, Alric M, Livrelli V, Blanquet-Diot S. Enterohemorrhagic Escherichia coli infection has donor-dependent effect on human gut microbiota and may be antagonized by probiotic yeast during interaction with Peyer's patches. Appl Microbiol Biotechnol 2015; 99:9097-110. [PMID: 26084888 DOI: 10.1007/s00253-015-6704-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Revised: 05/13/2015] [Accepted: 05/17/2015] [Indexed: 01/05/2023]
Abstract
Enterohemorrhagic Escherichia coli (EHEC) are major food-borne pathogens responsible for serious infections ranging from mild diarrhea to hemorrhagic colitis and life-threatening complications. Shiga toxins (Stxs) are the main virulence factor of EHEC. The antagonistic effect of a prophylactic treatment with the probiotic strain Saccharomyces cerevisiae against EHEC O157:H7 was investigated using complementary in vitro human colonic model and in vivo murine ileal loop assays. In vitro, the probiotic treatment had no effect on O157:H7 survival but favorably influenced gut microbiota activity through modulation of short-chain fatty acid production, increasing acetate production and decreasing that of butyrate. Both pathogen and probiotic strains had individual-dependent effects on human gut microbiota. For the first time, stx expression was followed in human colonic environment: at 9 and 12 h post EHEC infection, probiotic treatment significantly decreased stx mRNA levels. Besides, in murine ileal loops, the probiotic yeast specifically exerted a trophic effect on intestinal mucosa and inhibited O157:H7 interactions with Peyer's patches and subsequent hemorrhagic lesions. Taken together, the results suggest that S. cerevisiae may be useful in the fight against EHEC infection and that host associated factors such as microbiota could influence clinical evolution of EHEC infection and the effectiveness of probiotics.
Collapse
Affiliation(s)
- J Thévenot
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.,Centre de Recherche en Nutrition Humaine Auvergne, M2iSH, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte UMR INSERM / Université d'Auvergne U1071 USC-INRA 2018, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - C Cordonnier
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.,Centre de Recherche en Nutrition Humaine Auvergne, M2iSH, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte UMR INSERM / Université d'Auvergne U1071 USC-INRA 2018, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - A Rougeron
- Centre de Recherche en Nutrition Humaine Auvergne, M2iSH, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte UMR INSERM / Université d'Auvergne U1071 USC-INRA 2018, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - O Le Goff
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - H T T Nguyen
- Centre de Recherche en Nutrition Humaine Auvergne, M2iSH, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte UMR INSERM / Université d'Auvergne U1071 USC-INRA 2018, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - S Denis
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - M Alric
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - V Livrelli
- Centre de Recherche en Nutrition Humaine Auvergne, M2iSH, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte UMR INSERM / Université d'Auvergne U1071 USC-INRA 2018, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.,Service de Bactériologie, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - S Blanquet-Diot
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
| |
Collapse
|
42
|
Lodemann U, Strahlendorf J, Schierack P, Klingspor S, Aschenbach JR, Martens H. Effects of the Probiotic Enterococcus faecium and Pathogenic Escherichia coli Strains in a Pig and Human Epithelial Intestinal Cell Model. SCIENTIFICA 2015; 2015:235184. [PMID: 25883829 PMCID: PMC4391159 DOI: 10.1155/2015/235184] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Accepted: 03/05/2015] [Indexed: 06/04/2023]
Abstract
The aim of this study has been to elucidate the effect of the probiotic Enterococcus faecium NCIMB 10415 on epithelial integrity in intestinal epithelial cells and whether pre- and coincubation with this strain can reproducibly prevent damage induced by enterotoxigenic (ETEC) and enteropathogenic Escherichia coli (EPEC). Porcine (IPEC-J2) and human (Caco-2) intestinal epithelial cells were incubated with bacterial strains and epithelial integrity was assessed by measuring transepithelial electrical resistance (TEER) and mannitol flux rates. E. faecium alone increased TEER of Caco-2 cells without affecting mannitol fluxes whereas the E. coli strains decreased TEER and concomitantly increased mannitol flux rates in both cell lines. Preincubation with E. faecium had no effect on the TEER decrease induced by E. coli in preliminary experiments. However, in a second set of experiments using a slightly different protocol, E. faecium ameliorated the TEER decrease induced by ETEC at 4 h in IPEC-J2 and at 2, 4, and 6 h in Caco-2 cells. We conclude that E. faecium positively affected epithelial integrity in monoinfected Caco-2 cells and could ameliorate the damage on TEER induced by an ETEC strain. Reproducibility of the results is, however, limited when experiments are performed with living bacteria over longer periods.
Collapse
Affiliation(s)
- Ulrike Lodemann
- Institute of Veterinary Physiology, Faculty of Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, Germany
| | - Julia Strahlendorf
- Institute of Veterinary Physiology, Faculty of Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, Germany
| | - Peter Schierack
- Institute of Microbiology and Epizootics, Faculty of Veterinary Medicine, Freie Universität Berlin, 10115 Berlin, Germany
- Faculty of Natural Sciences, University of Applied Sciences, 01968 Senftenberg, Germany
| | - Shanti Klingspor
- Institute of Veterinary Physiology, Faculty of Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, Germany
| | - Jörg R. Aschenbach
- Institute of Veterinary Physiology, Faculty of Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, Germany
| | - Holger Martens
- Institute of Veterinary Physiology, Faculty of Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, Germany
| |
Collapse
|
43
|
Saccharomyces cerevisiae CNCM I-3856 prevents colitis induced by AIEC bacteria in the transgenic mouse model mimicking Crohn's disease. Inflamm Bowel Dis 2015; 21:276-86. [PMID: 25569734 DOI: 10.1097/mib.0000000000000280] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Adherent-invasive Escherichia coli (AIEC), which colonize the ileal mucosa of patients with Crohn's disease (CD), are able to adhere to and invade intestinal epithelial cells. Overexpression of the glycoprotein CEACAM6 on host cells favors AIEC attachment and inflammation. We investigated the ability of Saccharomyces cerevisiae CNCM I-3856 to inhibit AIEC adhesion and to reduce colitis. METHODS Adhesion experiments were performed on T84 cells and on enterocytes from patients with CD with AIEC LF82 in the presence of S. cerevisiae. Colonization and symptoms of colitis were assessed in LF82-infected transgenic CEABAC10 mice treated with live S. cerevisiae or S. cerevisiae derivatives. Proinflammatory cytokines were quantified by enzyme linked immunosorbent assay. Intestinal permeability was assessed by measuring the 4 kDa dextran-FITC flux in the serum. RESULTS S. cerevisiae strongly inhibited LF82 adhesion to T84 cells and to the brush border of CD enterocytes. Yeasts decreased LF82 colonization and colitis in CEABAC10 mice and restored barrier function through prevention of the LF82-induced expression of pore-forming tight junction claudin-2 at the plasma membrane of intestinal epithelial cells. These effects were accompanied by a decrease in proinflammatory cytokines IL-6, IL-1β, and KC release by the gut mucosa. Yeast derivatives exerted similar effects on LF82 colonization and colitis demonstrating that yeast viability was not essential to exert beneficial effects. CONCLUSIONS S. cerevisiae yeasts reduce colitis induced by AIEC bacteria in CEACAM6-expressing mice. Such a probiotic strategy could be envisaged in a subgroup of patients with CD abnormally expressing CEACAM6 at the ileal mucosa and therefore susceptible to being colonized by AIEC bacteria.
Collapse
|
44
|
Hudson LE, Fasken MB, McDermott CD, McBride SM, Kuiper EG, Guiliano DB, Corbett AH, Lamb TJ. Functional heterologous protein expression by genetically engineered probiotic yeast Saccharomyces boulardii. PLoS One 2014; 9:e112660. [PMID: 25391025 PMCID: PMC4229219 DOI: 10.1371/journal.pone.0112660] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2014] [Accepted: 10/20/2014] [Indexed: 02/07/2023] Open
Abstract
Recent studies have suggested the potential of probiotic organisms to be adapted for the synthesis and delivery of oral therapeutics. The probiotic yeast Saccharomyces boulardii would be especially well suited for this purpose due to its ability, in contrast to probiotic prokaryotes, to perform eukaryotic post translational modifications. This probiotic yeast thus has the potential to express a broad array of therapeutic proteins. Currently, however, use of wild type (WT) S. boulardii relies on antibiotic resistance for the selection of transformed yeast. Here we report the creation of auxotrophic mutant strains of S. boulardii that can be selected without antibiotics and demonstrate that these yeast can express functional recombinant protein even when recovered from gastrointestinal immune tissues in mice. A UV mutagenesis approach was employed to generate three uracil auxotrophic S. boulardii mutants that show a low rate of reversion to wild type growth. These mutants can express recombinant protein and are resistant in vitro to low pH, bile acid salts, and anaerobic conditions. Critically, oral gavage experiments using C57BL/6 mice demonstrate that mutant S. boulardii survive and are taken up into gastrointestinal immune tissues on a similar level as WT S. boulardii. Mutant yeast recovered from gastrointestinal immune tissues furthermore retain expression of functional recombinant protein. These data show that auxotrophic mutant S. boulardii can safely express recombinant protein without antibiotic selection and can deliver recombinant protein to gastrointestinal immune tissues. These auxotrophic mutants of S. boulardii pave the way for future experiments to test the ability of S. boulardii to deliver therapeutics and mediate protection against gastrointestinal disorders.
Collapse
Affiliation(s)
- Lauren E. Hudson
- Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America
| | - Milo B. Fasken
- Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, United States of America
| | - Courtney D. McDermott
- Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America
| | - Shonna M. McBride
- Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America
| | - Emily G. Kuiper
- Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, United States of America
| | - David B. Guiliano
- School of Health, Sport and Bioscience, University of East London, London, United Kingdom
| | - Anita H. Corbett
- Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, United States of America
| | - Tracey J. Lamb
- Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America
| |
Collapse
|
45
|
Pontier-Bres R, Munro P, Boyer L, Anty R, Imbert V, Terciolo C, André F, Rampal P, Lemichez E, Peyron JF, Czerucka D. Saccharomyces boulardii modifies Salmonella typhimurium traffic and host immune responses along the intestinal tract. PLoS One 2014; 9:e103069. [PMID: 25118595 PMCID: PMC4145484 DOI: 10.1371/journal.pone.0103069] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2013] [Accepted: 06/27/2014] [Indexed: 12/12/2022] Open
Abstract
Salmonella enterica serovar Typhimurium (ST) is an enteropathogenic Gram-negative bacterium that causes infection following oral ingestion. ST spreads rapidly along the gastrointestinal tract (GIT) and invades the intestinal epithelium to ultimately reach internal body organs. The probiotic yeast Saccharomyces boulardii BIOCODEX (S.b-B) is prescribed for prophylaxis of diarrheal infectious diseases. We previously showed that S.b-B prevents weight loss in ST-infected mice and significantly decreases bacterial translocation to the spleen and liver. This study was designed to investigate the effect of S.b-B on ST migration along the GIT and the impact of the yeast on the host's early innate immune responses. Bioluminescent imaging (BLI) was used to evaluate the effect of S.b-B on the progression of luminescent Salmonella Typhimurium (ST-lux) in the GIT of mice pretreated with streptomycin. Photonic emission (PE) was measured in GIT extracts (stomach, small intestine, cecum and colon) at various time periods post-infection (PI). PE analysis revealed that, 45 min PI, ST-lux had migrated slightly faster in the mice treated with S.b-B than in the untreated infected animals. At 90 min PI, ST-lux had reached the cecum in both groups of mice. Adhesion of ST to S.b-B was visualized in the intestines of the mice and probably accounts for (1) the faster elimination of ST-lux in the feces, and (2) reduced translocation of ST to the spleen and liver. In the early phase of infection, S.b-B also modifies the host's immune responses by (1) increasing IFN-γ gene expression and decreasing IL-10 gene expression in the small intestine, and (2) elevating both IFN-γ, and IL-10 mRNA levels in the cecum. BLI revealed that S.b-B modifies ST migration and the host immune response along the GIT. Study findings shed new light on the protective mechanisms of S.b-B during the early phase of Salmonella pathogenesis.
Collapse
Affiliation(s)
- Rodolphe Pontier-Bres
- INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 4 “Inflammation, Cancer, Cancer Stem Cells” Nice, France
- Université de Nice-Sophia Antipolis, UFR Médecine, IFR50, Faculté de Médecine, Nice, France
| | - Patrick Munro
- INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 6 “Microbial toxins in host pathogen interactions” Nice, France
- Université de Nice-Sophia Antipolis, UFR Médecine, IFR50, Faculté de Médecine, Nice, France
| | - Laurent Boyer
- INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 6 “Microbial toxins in host pathogen interactions” Nice, France
- Université de Nice-Sophia Antipolis, UFR Médecine, IFR50, Faculté de Médecine, Nice, France
| | - Rodolphe Anty
- INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 8 “Hepatic complications in obesity” Nice, France
- Université de Nice-Sophia Antipolis, UFR Médecine, IFR50, Faculté de Médecine, Nice, France
| | - Véronique Imbert
- INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 4 “Inflammation, Cancer, Cancer Stem Cells” Nice, France
- Université de Nice-Sophia Antipolis, UFR Médecine, IFR50, Faculté de Médecine, Nice, France
| | - Chloé Terciolo
- CRO2 INSERM U911, Campus Santé Timone, Université Aix-Marseille, Marseille, France
| | - Fréderic André
- CRO2 INSERM U911, Campus Santé Timone, Université Aix-Marseille, Marseille, France
| | | | - Emmanuel Lemichez
- INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 6 “Microbial toxins in host pathogen interactions” Nice, France
- Université de Nice-Sophia Antipolis, UFR Médecine, IFR50, Faculté de Médecine, Nice, France
| | - Jean-François Peyron
- INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 4 “Inflammation, Cancer, Cancer Stem Cells” Nice, France
- Université de Nice-Sophia Antipolis, UFR Médecine, IFR50, Faculté de Médecine, Nice, France
| | - Dorota Czerucka
- INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 4 “Inflammation, Cancer, Cancer Stem Cells” Nice, France
- Université de Nice-Sophia Antipolis, UFR Médecine, IFR50, Faculté de Médecine, Nice, France
- * E-mail:
| |
Collapse
|
46
|
Boonma P, Spinler JK, Venable SF, Versalovic J, Tumwasorn S. Lactobacillus rhamnosus L34 and Lactobacillus casei L39 suppress Clostridium difficile-induced IL-8 production by colonic epithelial cells. BMC Microbiol 2014; 14:177. [PMID: 24989059 PMCID: PMC4094603 DOI: 10.1186/1471-2180-14-177] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2014] [Accepted: 06/18/2014] [Indexed: 01/01/2023] Open
Abstract
Background Clostridium difficile is the main cause of hospital-acquired diarrhea and colitis known as C. difficile-associated disease (CDAD).With increased severity and failure of treatment in CDAD, new approaches for prevention and treatment, such as the use of probiotics, are needed. Since the pathogenesis of CDAD involves an inflammatory response with a massive influx of neutrophils recruited by interleukin (IL)-8, this study aimed to investigate the probiotic effects of Lactobacillus spp. on the suppression of IL-8 production in response to C. difficile infection. Results We screened Lactobacillus conditioned media from 34 infant fecal isolates for the ability to suppress C. difficile-induced IL-8 production from HT-29 cells. Factors produced by two vancomycin-resistant lactobacilli, L. rhamnosus L34 (LR-L34) and L.casei L39 (LC-L39), suppressed the secretion and transcription of IL-8 without inhibiting C. difficile viability or toxin production. Conditioned media from LR-L34 suppressed the activation of phospho-NF-κB with no effect on phospho-c-Jun. However, LC-L39 conditioned media suppressed the activation of both phospho-NF-κB and phospho-c-Jun. Conditioned media from LR-L34 and LC-L39 also decreased the production of C. difficile-induced GM-CSF in HT-29 cells. Immunomodulatory factors present in the conditioned media of both LR-L34 and LC-L39 are heat-stable up to 100°C and > 100 kDa in size. Conclusions Our results suggest that L. rhamnosus L34 and L. casei L39 each produce factors capable of modulating inflammation stimulated by C. difficile. These vancomycin-resistant Lactobacillus strains are potential probiotics for treating or preventing CDAD.
Collapse
Affiliation(s)
| | | | | | | | - Somying Tumwasorn
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
| |
Collapse
|
47
|
Abbas Z, Yakoob J, Jafri W, Ahmad Z, Azam Z, Usman MW, Shamim S, Islam M. Cytokine and clinical response to Saccharomyces boulardii therapy in diarrhea-dominant irritable bowel syndrome: a randomized trial. Eur J Gastroenterol Hepatol 2014; 26:630-639. [PMID: 24722560 DOI: 10.1097/meg.0000000000000094] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION This preliminary study aimed to investigate the effects of the probiotic Saccharomyces boulardii on proinflammatory and anti-inflammatory cytokines in patients with diarrhea-dominant irritable bowel syndrome (IBS-D). The other objectives were to document any clinical improvement as judged by symptoms, quality of life, and histology. PATIENTS AND METHODS This was a randomized, double blind, placebo-controlled trial in which S. boulardii, 750 mg/day, or placebo was administered for 6 weeks in IBS-D patients, in addition to ispaghula husk standard treatment. RESULTS Thirty-seven patients received S. boulardii and 35 patients received the placebo. As compared with placebo, the S. boulardii group showed a significant decrease in blood and tissue levels of proinflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor-α (P<0.001) and an increase in anti-inflammatory IL-10 levels, as well as an increase in the tissue IL-10/IL-12 ratio (P<0.001). No significant change in the blood and tissue levels of cytokines was found in the placebo group. Bowel-related IBS-D symptoms reported in the patients' daily diary improved in both groups. However, overall improvement in the quality of life was more marked in the S. boulardii group. Although baseline histological findings were mild, an improvement was observed in the probiotic group in the lymphocyte and neutrophil infiltrates (P=0.017 and 0.018), epithelial mitosis (P=0.003), and intraepithelial lymphocytes (P=0.024). No serious adverse events were found in either group. CONCLUSION S. boulardii with ispaghula husk was superior to placebo with ispaghula husk in improving the cytokine profile, histology, and quality of life of patients with IBS-D. These preliminary results need to be confirmed in a well-powered trial.
Collapse
Affiliation(s)
- Zaigham Abbas
- Departments of aMedicine bPathology cCommunity Health Sciences, The Aga Khan University Hospital, Karachi, Pakistan
| | | | | | | | | | | | | | | |
Collapse
|
48
|
Smith IM, Christensen JE, Arneborg N, Jespersen L. Yeast modulation of human dendritic cell cytokine secretion: an in vitro study. PLoS One 2014; 9:e96595. [PMID: 24816850 PMCID: PMC4015989 DOI: 10.1371/journal.pone.0096595] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Accepted: 04/10/2014] [Indexed: 02/07/2023] Open
Abstract
Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The concept of individual microorganisms influencing the makeup of T cell subsets via interactions with intestinal dendritic cells (DCs) appears to constitute the foundation for immunoregulatory effects of probiotics, and several studies have reported probiotic strains resulting in reduction of intestinal inflammation through modulation of DC function. Consequent to a focus on Saccharomyces boulardii as the fundamental probiotic yeast, very little is known about hundreds of non-Saccharomyces yeasts in terms of their interaction with the human gastrointestinal immune system. The aim of the present study was to evaluate 170 yeast strains representing 75 diverse species for modulation of inflammatory cytokine secretion by human DCs in vitro, as compared to cytokine responses induced by a S. boulardii reference strain with probiotic properties documented in clinical trials. Furthermore, we investigated whether cytokine inducing interactions between yeasts and human DCs are dependent upon yeast viability or rather a product of membrane interactions regardless of yeast metabolic function. We demonstrate high diversity in yeast induced cytokine profiles and employ multivariate data analysis to reveal distinct clustering of yeasts inducing similar cytokine profiles in DCs, highlighting clear species distinction within specific yeast genera. The observed differences in induced DC cytokine profiles add to the currently very limited knowledge of the cross-talk between yeasts and human immune cells and provide a foundation for selecting yeast strains for further characterization and development toward potentially novel yeast probiotics. Additionally, we present data to support a hypothesis that the interaction between yeasts and human DCs does not solely depend on yeast viability, a concept which may suggest a need for further classifications beyond the current definition of a probiotic.
Collapse
Affiliation(s)
- Ida M. Smith
- Health & Nutrition Division Discovery, Chr. Hansen A/S, Hørsholm, Denmark
- Department of Food Science, University of Copenhagen, Frederiksberg, Denmark
| | | | - Nils Arneborg
- Department of Food Science, University of Copenhagen, Frederiksberg, Denmark
| | - Lene Jespersen
- Department of Food Science, University of Copenhagen, Frederiksberg, Denmark
- * E-mail:
| |
Collapse
|
49
|
Saxena A, Sitaraman R. Osmoregulation and the human mycobiome. Front Microbiol 2014; 5:167. [PMID: 24860554 PMCID: PMC4028996 DOI: 10.3389/fmicb.2014.00167] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2014] [Accepted: 03/27/2014] [Indexed: 11/18/2022] Open
Affiliation(s)
- Abhishek Saxena
- Department of Biotechnology, TERI University New Delhi, India
| | | |
Collapse
|
50
|
Ji J, Hu S, Zheng M, Du W, Shang Q, Li W. Bacillus amyloliquefaciens SC06 inhibits ETEC-induced pro-inflammatory responses by suppression of MAPK signaling pathways in IPEC-1 cells and diarrhea in weaned piglets. Livest Sci 2013. [DOI: 10.1016/j.livsci.2013.09.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
|