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Malik S, Naqvi SAA, Shadali AH, Khan H, Christof M, Niu C, Schwartz DA, Adler DG. Fecal Microbiota Transplantation (FMT) and Clinical Outcomes Among Inflammatory Bowel Disease (IBD) Patients: An Umbrella Review. Dig Dis Sci 2025:10.1007/s10620-025-08946-8. [PMID: 40038211 DOI: 10.1007/s10620-025-08946-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 02/19/2025] [Indexed: 03/06/2025]
Abstract
BACKGROUND AND AIMS Recent systematic reviews and meta-analyses (SRMAs) have shown inconsistent effectiveness of FMT among patients with IBD. This study aimed to appraise the evidence for clinically relevant outcomes with FMT in patients with IBD using published SRMAs. METHODS We searched major databases from inception through Nov 2023 to identify SRMAs assessing the effectiveness of FMT in patients with IBD. Primary outcomes included clinical remission, clinical response, endoscopic remission/response, a composite endpoint, and adverse effects. We included SRMAs investigating FMT's effect in patients with IBD using RCTs and observational studies data. Methodological quality and evidence certainty were assessed using AMSTAR 2 and GRADE. RESULTS Out of 106 citations, 16 SRMAs were included with varying study sizes (2 to 60 primary studies) and participants (112 to 1169 per SRMA). Five SRMAs assessed FMT in IBD, while 11 focused on Ulcerative Colitis (UC). Seven SRMAs included RCTs only, and nine included both RCTs and observational studies. Methodological quality was critically low in 9 SRMAs (56%) and low in 7 studies (44%). FMT showed clinical remission benefit in all 16 SRMAs, with varying certainty: 3 high, 4 moderate, 4 low, and 5 very low. Endoscopic remission/response was reported in 5 meta-analyses on UC, with 1 high, 3 moderate, and 1 very low certainty. Combined clinical remission and endoscopic response were reported in 3 SRMAs on UC, with 1 low and 2 moderate certainty. Adverse events were reported in 6 SRMAs, with 1 high, 3 moderate, 1 low, and 1 very low certainty. CONCLUSION Current evidence shows potential benefits of FMT in IBD, particularly UC, supported by significant associations in 16 meta-analyses. However, poor methodological quality and variability in evidence certainty call for high-quality RCTs to strengthen the evidence.
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Affiliation(s)
- Sheza Malik
- Internal Medicine, Rochester General Hospital, Rochester, NY, USA
| | | | | | - Hajra Khan
- Rawalpindi Medical College, Rawalpindi, Pakistan
| | | | - Chengu Niu
- Internal Medicine, Rochester General Hospital, Rochester, NY, USA
| | - David A Schwartz
- Gastroenterology and Hepatology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Douglas G Adler
- Gastroenterology and Hepatology, Porter Adventist Hospital in Denver, Denver, CO, USA.
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Men J, Li H, Cui C, Ma X, Liu P, Yu Z, Gong X, Yao Y, Ren J, Zhao C, Song B, Yin K, Wu J, Liu W. Fecal bacteria transplantation replicates aerobic exercise to reshape the gut microbiota in mice to inhibit high-fat diet-induced atherosclerosis. PLoS One 2025; 20:e0314698. [PMID: 39903739 PMCID: PMC11793757 DOI: 10.1371/journal.pone.0314698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 11/14/2024] [Indexed: 02/06/2025] Open
Abstract
Aerobic exercise exerts a significant impact on the gut microbiota imbalance and atherosclerosis induced by a high-fat diet. However, whether fecal microbiota transplantation, based on aerobic exercise, can improve atherosclerosis progression remains unexplored. In this study, we utilized male C57 mice to establish models of aerobic exercise and atherosclerosis, followed by fecal microbiota transplantation(Fig 1a). Firstly, we analyzed the body weight, somatotype, adipocyte area, and aortic HE images of the model mice. Our findings revealed that high-fat diet -induced atherosclerosis mice exhibited elevated lipid accumulation, larger adipocyte area, and more severe atherosclerosis progression. Additionally, we assessed plasma lipid levels, inflammatory factors, and gut microbiota composition in each group of mice. high-fat diet -induced atherosclerosis mice displayed dyslipidemia along with inflammatory responses and reduced gut microbiota diversity as well as abundance of beneficial bacteria. Subsequently performing fecal microbiota transplantation demonstrated that high-fat diet -induced atherosclerosis mice experienced weight loss accompanied by reduced lipid accumulation while normalizing their gut microbiota profile; furthermore it significantly improved blood lipids and inflammation markers thereby exhibiting notable anti- atherosclerosis effects. The findings suggest that aerobic exercise can modify gut microbiota composition and improve high-fat diet-induced atherosclerosis(Fig 1b). Moreover, these beneficial effects can be effectively transmitted through fecal microbiota transplantation, offering a promising therapeutic approach for managing atherosclerosis.
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Affiliation(s)
- Jie Men
- Fenyang College of Shanxi Medical University, Fenyang, PR China
| | - Hao Li
- Fenyang College of Shanxi Medical University, Fenyang, PR China
| | - Chenglong Cui
- Fenyang College of Shanxi Medical University, Fenyang, PR China
| | - Xuedi Ma
- Fenyang College of Shanxi Medical University, Fenyang, PR China
| | - Penghong Liu
- First Hospital of Shanxi Medical University, Taiyuan, PR China
| | - Zhengyang Yu
- Fenyang College of Shanxi Medical University, Fenyang, PR China
| | - Xueyan Gong
- Third Hospital of Shanxi Medical University, Taiyuan, PR China
| | - Youhao Yao
- Fifth Hospital of Shanxi Medical University, Taiyuan, PR China
| | - Jieying Ren
- First Hospital of Shanxi Medical University, Taiyuan, PR China
| | - Chengrui Zhao
- Fenyang College of Shanxi Medical University, Fenyang, PR China
| | - Binyu Song
- Fenyang College of Shanxi Medical University, Fenyang, PR China
| | - Kaijiang Yin
- Fenyang College of Shanxi Medical University, Fenyang, PR China
| | - Jianting Wu
- Fenyang College of Shanxi Medical University, Fenyang, PR China
| | - Wei Liu
- Anhui Agricultural University, Hefei, PR China
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Shang J, Del Valle DM, Britton GJ, Mead K, Rajpal U, Chen-Liaw A, Mogno I, Li Z, Menon R, Gonzalez-Kozlova E, Elkrief A, Peled JU, Gonsalves TR, Shah NJ, Postow M, Colombel JF, Gnjatic S, Faleck DM, Faith JJ. Baseline colitogenicity and acute perturbations of gut microbiota in immunotherapy-related colitis. J Exp Med 2025; 222:e20232079. [PMID: 39666007 PMCID: PMC11636624 DOI: 10.1084/jem.20232079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 09/17/2024] [Accepted: 11/21/2024] [Indexed: 12/13/2024] Open
Abstract
Immunotherapy-related colitis (irC) frequently emerges as an immune-related adverse event during immune checkpoint inhibitor therapy and is presumably influenced by the gut microbiota. We longitudinally studied microbiomes from 38 ICI-treated cancer patients. We compared 13 ICI-treated subjects who developed irC against 25 ICI-treated subjects who remained irC-free, along with a validation cohort. Leveraging a preclinical mouse model, predisease stools from irC subjects induced greater colitigenicity upon transfer to mice. The microbiota during the first 10 days of irC closely resembled inflammatory bowel disease microbiomes, with reduced diversity, increased Proteobacteria and Veillonella, and decreased Faecalibacterium, which normalized before irC remission. These findings highlight the irC gut microbiota as functionally distinct but phylogenetically similar to non-irC and healthy microbiomes, with the exception of an acute, transient disruption early in irC. We underscore the significance of longitudinal microbiome profiling in developing clinical avenues to detect, monitor, and mitigate irC in ICI therapy cancer patients.
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Affiliation(s)
- Joan Shang
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Diane Marie Del Valle
- Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Graham J. Britton
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - K.R. Mead
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Urvija Rajpal
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Alice Chen-Liaw
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ilaria Mogno
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Zhihua Li
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Edgar Gonzalez-Kozlova
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Arielle Elkrief
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jonathan U. Peled
- Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Cornell Medical College, New York, NY, USA
| | - Tina Ruth Gonsalves
- Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Neil J. Shah
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Cornell Medical College, New York, NY, USA
| | - Michael Postow
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Cornell Medical College, New York, NY, USA
| | - Jean-Frederic Colombel
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Sacha Gnjatic
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - David M. Faleck
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Cornell Medical College, New York, NY, USA
| | - Jeremiah J. Faith
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Chen P, Jiang X, Fu J, Ou C, Li Y, Jia J, Liao C. The potential mechanism of action of gut flora and bile acids through the TGR5/TRPV1 signaling pathway in diabetic peripheral neuropathic pain. Front Endocrinol (Lausanne) 2024; 15:1419160. [PMID: 39619328 PMCID: PMC11604420 DOI: 10.3389/fendo.2024.1419160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 10/22/2024] [Indexed: 12/13/2024] Open
Abstract
Diabetic peripheral neuropathic pain (DPNP) is a major complication of diabetes that markedly affects the quality of life and health status of patients. Recent studies have investigated the potential regulatory influence of gut flora and bile acids on DPNP via the TGR5/TRPV1 signaling pathway. Dysbiosis of the gut flora not only directly affects bile acid metabolism but also significantly correlates with diabetes-associated neuropathy through interactions with the bile acid receptor TGR5 and the ion channel TRPV1. This review describes how alterations in the gut flora and bile acid metabolism contribute to the pathogenesis of DPNP through the TGR5/TRPV1 signaling pathway, revealing potential applications for this pathway in DPNP management. Furthermore, experimental and clinical studies have demonstrated the modulation of gut flora and bile acid metabolism as well as targeting the TGR5/TRPV1 signaling pathway as an innovative therapeutic approach. Further studies are warranted to elucidate the underlying mechanism and develop treatment modalities based on gut flora regulation and signaling pathway interventions, thus providing novel insights and approaches for DPNP therapy.
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Affiliation(s)
- Peng Chen
- Department of Pediatrics, Southwest Medical University, Luzhou, Sichuan, China
| | - Xian Jiang
- Department of Anesthesiology, Luzhou People’s Hospital, Luzhou, Sichuan, China
| | - Jia Fu
- Department of Pain Management, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China
| | - Cehua Ou
- Department of Pain Management, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China
| | - Yao Li
- Department of Science and Technology, Southwest Medical University, Luzhou, Sichuan, China
| | - Jing Jia
- Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China
- Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China
| | - Changli Liao
- Department of Science and Technology, Southwest Medical University, Luzhou, Sichuan, China
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Li S, Zhu S, Yu J. The role of gut microbiota and metabolites in cancer chemotherapy. J Adv Res 2024; 64:223-235. [PMID: 38013112 PMCID: PMC11464465 DOI: 10.1016/j.jare.2023.11.027] [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: 08/03/2023] [Revised: 11/23/2023] [Accepted: 11/24/2023] [Indexed: 11/29/2023] Open
Abstract
BACKGROUND The microbiota inhabits the epithelial surfaces of hosts, which influences physiological functions from helping digest food and acquiring nutrition to regulate metabolism and shaping host immunity. With the deep insight into the microbiota, an increasing amount of research reveals that it is also involved in the initiation and progression of cancer. Intriguingly, gut microbiota can mediate the biotransformation of drugs, thereby altering their bioavailability, bioactivity, or toxicity. AIM OF REVIEW The review aims to elaborate on the role of gut microbiota and microbial metabolites in the efficacy and adverse effects of chemotherapeutics. Furthermore, we discuss the clinical potential of various ways to harness gut microbiota for cancer chemotherapy. KEY SCIENTIFIC CONCEPTS OF REVIEW Recent evidence shows that gut microbiota modulates the efficacy and toxicity of chemotherapy agents, leading to diverse host responses to chemotherapy. Thereinto, targeting the microbiota to improve efficacy and diminish the toxicity of chemotherapeutic drugs may be a promising strategy in tumor treatment.
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Affiliation(s)
- Shiyu Li
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK-Shenzhen research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Shuangli Zhu
- Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jun Yu
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK-Shenzhen research Institute, The Chinese University of Hong Kong, Hong Kong, China.
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Yamada CH, Ortis GB, Buso GM, Martins TC, Zequinao T, Telles JP, Wollmann LC, Montenegro CDO, Dantas LR, Cruz JW, Tuon FF. Validation of Lyophilized Human Fecal Microbiota for the Treatment of Clostridioides difficile Infection: A Pilot Study with Pharmacoeconomic Analysis of a Middle-Income Country-Promicrobioma Project. Microorganisms 2024; 12:1741. [PMID: 39203583 PMCID: PMC11356882 DOI: 10.3390/microorganisms12081741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 08/09/2024] [Accepted: 08/21/2024] [Indexed: 09/03/2024] Open
Abstract
BACKGROUND Clostridioides difficile infection (CDI) represents a prevalent and potentially severe health concern linked to the usage of broad-spectrum antibiotics. The aim of this study was to evaluate a new lyophilized product based on human fecal microbiota for transplant, including cost-benefit analysis in the treatment of recurrent or refractory CDI. METHODS The product for fecal microbiota transplant was obtained from two donors. Microbiological, viability, and genomic analysis were evaluated. After validation, a clinical pilot study including recurrent or refractory CDI with 24 patients was performed. Clinical response and 4-week recurrence were the outcome. Cost-benefit analysis compared the fecal microbiota transplant with conventional retreatment with vancomycin or metronidazole. RESULTS The microbiota for transplant presented significant bacterial viability, with and adequate balance of Firmicutes and Bacteroidetes. The clinical response with the microbiota transplant was 92%. In financial terms, estimated expenditure for CDI solely related to recurrence, based on stochastic modeling, totals USD 222.8 million per year in Brazil. CONCLUSIONS The lyophilized human fecal microbiota for transplant is safe and can be an important step for a new product with low cost, even with genomic sequencing. Fecal microbiota transplantation emerges as a more cost-effective alternative compared to antimicrobials in the retreatment of CDI.
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Affiliation(s)
- Carolina Hikari Yamada
- Laboratory of Emerging Infectious Diseases, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, PR, Brazil; (C.H.Y.); (G.B.O.); (T.C.M.); (T.Z.); (L.R.D.)
| | - Gabriel Burato Ortis
- Laboratory of Emerging Infectious Diseases, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, PR, Brazil; (C.H.Y.); (G.B.O.); (T.C.M.); (T.Z.); (L.R.D.)
| | - Gustavo Martini Buso
- School of Business, Pontifical Catholic University of Paraná, Rua Imaculada Conceição 1155, Curitiba 80215-901, PR, Brazil; (G.M.B.); (J.W.C.)
| | - Thalissa Colodiano Martins
- Laboratory of Emerging Infectious Diseases, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, PR, Brazil; (C.H.Y.); (G.B.O.); (T.C.M.); (T.Z.); (L.R.D.)
| | - Tiago Zequinao
- Laboratory of Emerging Infectious Diseases, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, PR, Brazil; (C.H.Y.); (G.B.O.); (T.C.M.); (T.Z.); (L.R.D.)
| | - Joao Paulo Telles
- Hospital Universitário Evangélico Mackenzie, Curitiba 80730-150, PR, Brazil; (J.P.T.); (L.C.W.)
| | | | - Carolina de Oliveira Montenegro
- School of Business, Pontifical Catholic University of Paraná, Rua Imaculada Conceição 1155, Curitiba 80215-901, PR, Brazil; (G.M.B.); (J.W.C.)
| | - Leticia Ramos Dantas
- Laboratory of Emerging Infectious Diseases, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, PR, Brazil; (C.H.Y.); (G.B.O.); (T.C.M.); (T.Z.); (L.R.D.)
| | - June Westarb Cruz
- School of Business, Pontifical Catholic University of Paraná, Rua Imaculada Conceição 1155, Curitiba 80215-901, PR, Brazil; (G.M.B.); (J.W.C.)
| | - Felipe Francisco Tuon
- Laboratory of Emerging Infectious Diseases, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, PR, Brazil; (C.H.Y.); (G.B.O.); (T.C.M.); (T.Z.); (L.R.D.)
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Tan S, Zhang W, Zeng P, Yang Y, Chen S, Li Y, Bian Y, Xu C. Clinical effects of chemical drugs, fecal microbiota transplantation, probiotics, dietary fiber, and acupuncture in the treatment of chronic functional constipation: a systematic review and network meta-analysis. Eur J Gastroenterol Hepatol 2024; 36:815-830. [PMID: 38829940 DOI: 10.1097/meg.0000000000002786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/05/2024]
Abstract
Currently, there are increasingly diverse treatment modalities for chronic functional constipation (CFC). This study aims to compare the relative efficacy and safety of chemical drugs, fecal microbiota transplantation (FMT), probiotics, dietary fiber, and acupuncture in the treatment of patients with CFC. We searched relevant randomized controlled trials (RCTs) published in five databases up to November 2023. Network meta-analysis (NMA) was carried out using R Studio 4.2.1. Cumulative ranking probability plots, assessed through the surface under the cumulative ranking (SUCRA), were employed to rank the included drugs for various outcome measures. We included a total of 45 RCT studies with 17 118 patients with CFC. From the SUCRA values and NMA results FMT showed the best utility in terms of clinical efficacy, Bristol stool form scale scores, patient assessment of constipation quality of life scores, and the treatment modality with the lowest ranked incidence of adverse effects was electroacupuncture. Subgroup analysis of the chemotherapy group showed that sodium A subgroup analysis of the chemical group showed that sodium picosulfate 10 mg had the highest clinical efficacy. FMT is more promising in the treatment of CFC and may be more effective in combination with the relatively safe treatment of acupuncture.
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Affiliation(s)
- Shufa Tan
- Shaanxi University of Traditional Chinese Medicine, Xianyang
| | - Wei Zhang
- Shaanxi University of Traditional Chinese Medicine, Xianyang
| | - Pengfei Zeng
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu
| | - Yunyi Yang
- Shanghai University of Traditional Chinese Medicine, Shanghai
| | - Shikai Chen
- Shanghai University of Traditional Chinese Medicine, Shanghai
| | - Yuwei Li
- Department of Colorectal Surgery, Tianjin Union Medical Center
| | - Yuhong Bian
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Chen Xu
- Department of Colorectal Surgery, Tianjin Union Medical Center
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Ruiz A, Gisbert E, Andree KB. Impact of the diet in the gut microbiota after an inter-species microbial transplantation in fish. Sci Rep 2024; 14:4007. [PMID: 38369563 PMCID: PMC10874947 DOI: 10.1038/s41598-024-54519-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 02/13/2024] [Indexed: 02/20/2024] Open
Abstract
Inter-species microbial transplantations offer the possibility of transferring species-specific microbes and their associated functionality. As a conceptual approach, an intestinal microbiota transplant (IMT) between two marine carnivorous fish species that thrive in different environmental conditions was conducted: from donor Atlantic salmon (Salmo salar) to recipient gilthead seabream (Sparus aurata), after obliterating its basal microbiota with an antibiotic treatment. To confirm that the gut microbiota was able to recover after antibiotics without the influence of the diet, a group of gilthead seabream not submitted to the IMT was kept fasted as an internal control. To assess the effect of the diet after the IMT, two groups of gilthead seabream were respectively fed with their typical diet and with Atlantic salmon diet. At 36 days post-IMT, the gut of the individuals fed with their typical diet was dominated by the feed-associated bacteria, while those fed with the salmon diet had developed a unique microbiota from the convergence of the diet, donor, and recipient microbiota. These results suggested that an intestinal microbiota transplantation may be effective if the basal microbiota from the gut is first cleared and a targeted dietary modification is provided to maintain and enrich the novel bacteria species over time.
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Affiliation(s)
- Alberto Ruiz
- Aquaculture Program, Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Centre de La Ràpita, Crta. Poble Nou, km 5.5, 43540, La Ràpita, Spain.
| | - Enric Gisbert
- Aquaculture Program, Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Centre de La Ràpita, Crta. Poble Nou, km 5.5, 43540, La Ràpita, Spain
| | - Karl B Andree
- Aquaculture Program, Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Centre de La Ràpita, Crta. Poble Nou, km 5.5, 43540, La Ràpita, Spain
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Zhou X, Chen R, Cai Y, Chen Q. Fecal Microbiota Transplantation: A Prospective Treatment for Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes 2024; 17:647-659. [PMID: 38347911 PMCID: PMC10860394 DOI: 10.2147/dmso.s447784] [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: 11/01/2023] [Accepted: 01/23/2024] [Indexed: 02/15/2024] Open
Abstract
Purpose of Review The aim of this review is to summarize the role of gastrointestinal microbiome (GM) in the development of type 2 diabetes mellitus (T2DM). Besides, we discuss the feasibility of applying FMT in the treatment of T2DM and propose a series of processes to refine the use of FMT in the treatment of T2DM. Recent Findings T2DM is a metabolic disease which is connected with the GM. According to many researches, GM can produce a variety of metabolites such as bile acid, short chain fatty acids, lipopolysaccharides and trimethylamine oxide which play an important role in metabolism. FMT is a method to regulate GM and has been observed to be effective in the treatment of metabolic diseases such as T2DM in some mouse models and people. However, there is still a lack of direct evidence for the use of FMT in the treatment of T2DM, and the process of FMT is not standardized. Summary Dysregulation of GM is closely related to the development of T2DM. Promoting the conversion of GM in T2DM patients to normal population through FMT can reduce insulin resistance and lower their blood glucose level, which is an optional treatment for T2DM patients in the future. At present, the feasibility and limitations of applying FMT to the treatment of T2DM need to be further studied.
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Affiliation(s)
- Xiaolan Zhou
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Rumeng Chen
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China
| | - Yichen Cai
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Qiu Chen
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
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10
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Zhou Y, Liu X, Gao W, Luo X, Lv J, Wang Y, Liu D. The role of intestinal flora on tumor immunotherapy: recent progress and treatment implications. Heliyon 2024; 10:e23919. [PMID: 38223735 PMCID: PMC10784319 DOI: 10.1016/j.heliyon.2023.e23919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 12/08/2023] [Accepted: 12/15/2023] [Indexed: 01/16/2024] Open
Abstract
Immunotherapy, specifically immune checkpoint inhibitors, has emerged as a promising approach for treating malignant tumors. The gut, housing approximately 70 % of the body's immune cells, is abundantly populated with gut bacteria that actively interact with the host's immune system. Different bacterial species within the intestinal flora are in a delicate equilibrium and mutually regulate each other. However, when this balance is disrupted, pathogenic microorganisms can dominate, adversely affecting the host's metabolism and immunity, ultimately promoting the development of disease. Emerging researches highlight the potential of interventions such as fecal microflora transplantation (FMT) to improve antitumor immune response and reduce the toxicity of immunotherapy. These remarkable findings suggest the major role of intestinal flora in the development of cancer immunotherapy and led us to the hypothesis that intestinal flora transplantation may be a new breakthrough in modifying immunotherapy side effects.
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Affiliation(s)
- Yimin Zhou
- School of Basic Medical Sciences, Shandong University, Jinan 250011, China
| | - Xiangdong Liu
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Wei Gao
- School of Basic Medical Sciences, Shandong University, Jinan 250011, China
| | - Xin Luo
- School of Basic Medical Sciences, Shandong University, Jinan 250011, China
| | - Junying Lv
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Yunshan Wang
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Duanrui Liu
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
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11
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Tang X, de Vos P. Structure-function effects of different pectin chemistries and its impact on the gastrointestinal immune barrier system. Crit Rev Food Sci Nutr 2023; 65:1201-1215. [PMID: 38095591 DOI: 10.1080/10408398.2023.2290230] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/25/2025]
Abstract
The gastrointestinal immune system is crucial for overall health, safeguarding the human body against harmful substances and pathogens. One key player in this defense is dietary fiber pectin, which supports the gut's immune barrier and fosters beneficial gut bacteria. Pectin's composition, including degree of methylation (DM), RG-I, and neutral sugar content, influences its health benefits. This review assesses how pectin composition impacts the gastrointestinal immune barrier and what advantages specific chemistries of pectin has for metabolic, cardiovascular, and immune health. We delve into recent findings regarding pectin's interactions with the immune system, including receptors like TLRs and galectin 3. Pectin is shown to fortify mucosal and epithelial layers, but the specific effects are structure dependent. Additionally, we explore potential strategies for enhancing the gut immune barrier function. Understanding how distinct pectin chemistries affect the gastrointestinal immune system is vital for developing preventive and therapeutic solutions for conditions related to microbiota imbalances and immune issues. Ultimately, this review offers insights into strategies to boost the gut immune barrier's effectiveness, fostering better overall health by using specific pectins in the diet.
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Affiliation(s)
- X Tang
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - P de Vos
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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12
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Liu X, Liu M, Zhao M, Li P, Gao C, Fan X, Cai G, Lu Q, Chen X. Fecal microbiota transplantation for the management of autoimmune diseases: Potential mechanisms and challenges. J Autoimmun 2023; 141:103109. [PMID: 37690971 DOI: 10.1016/j.jaut.2023.103109] [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: 01/17/2023] [Revised: 08/17/2023] [Accepted: 08/28/2023] [Indexed: 09/12/2023]
Abstract
Autoimmune diseases (AIDs) are a series of immune-mediated lethal diseases featured by over-activated immune cells attacking healthy self-tissues and organs due to the loss of immune tolerance, which always causes severe irreversible systematical organ damage and threatens human health heavily. To date, there are still no definitive cures for the treatment of AIDs due to their pathogenesis has not been clearly understood. Besides, the current clinical treatments of AIDs majorly rely on glucocorticoids and immune suppressors, which can lead to serious side effects. In the past years, there are increasing studies demonstrating that an imbalance of gut microbiota is intimately related to the pathogenesis of various AIDs, shedding light on the development of therapeutics by targeting the gut microbiota for the management of AIDs. Among all the approaches targeting the gut microbiota, fecal microbiota transplantation (FMT) has attracted increasing interest, and it has been proposed as a possible strategy to intervene in the homeostasis of gut microbiota for the treatment of various diseases. However, despite the reported good curative effects and clinical studies conducted on FMT, the detailed mechanisms of FMT for the effective treatment of those diseases have not been figured out. To fully understand the mechanisms of the therapeutic effects of FMT on AIDs and improve the therapeutic efficacy of FMT treatment, a systematic review of this topic is necessary. Hence, in this review paper, the potential mechanisms of FMT for the treatment of various AIDs were summarized, including promotion, shaping, activation, or inhibition of the host immune system via the interactions between the microorganisms and the gut immune system, gut-brain, gut-liver, gut-kidney axis, and so on. Then, applications of FMT for the treatment of various AIDs were detailed presented. Finally, the current challenges and potential solutions for the development of FMT formulations and FMT therapeutics were comprehensively discussed.
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Affiliation(s)
- Xiaomin Liu
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, PR China
| | - Mei Liu
- Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, PR China
| | - Ming Zhao
- Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, PR China; Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, 421142, PR China
| | - Ping Li
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, PR China
| | - Changxing Gao
- Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, PR China
| | - Xinyu Fan
- Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, PR China
| | - Guangyan Cai
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, PR China.
| | - Qianjin Lu
- Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, PR China; Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, 421142, PR China.
| | - Xiangmei Chen
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, PR China.
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13
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Huang G, Khan R, Zheng Y, Lee PC, Li Q, Khan I. Exploring the role of gut microbiota in advancing personalized medicine. Front Microbiol 2023; 14:1274925. [PMID: 38098666 PMCID: PMC10720646 DOI: 10.3389/fmicb.2023.1274925] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 11/15/2023] [Indexed: 12/17/2023] Open
Abstract
Ongoing extensive research in the field of gut microbiota (GM) has highlighted the crucial role of gut-dwelling microbes in human health. These microbes possess 100 times more genes than the human genome and offer significant biochemical advantages to the host in nutrient and drug absorption, metabolism, and excretion. It is increasingly clear that GM modulates the efficacy and toxicity of drugs, especially those taken orally. In addition, intra-individual variability of GM has been shown to contribute to drug response biases for certain therapeutics. For instance, the efficacy of cyclophosphamide depends on the presence of Enterococcus hirae and Barnesiella intestinihominis in the host intestine. Conversely, the presence of inappropriate or unwanted gut bacteria can inactivate a drug. For example, dehydroxylase of Enterococcus faecalis and Eggerthella lenta A2 can metabolize L-dopa before it converts into the active form (dopamine) and crosses the blood-brain barrier to treat Parkinson's disease patients. Moreover, GM is emerging as a new player in personalized medicine, and various methods are being developed to treat diseases by remodeling patients' GM composition, such as prebiotic and probiotic interventions, microbiota transplants, and the introduction of synthetic GM. This review aims to highlight how the host's GM can improve drug efficacy and discuss how an unwanted bug can cause the inactivation of medicine.
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Affiliation(s)
- Gouxin Huang
- Clinical Research Center, Shantou Central Hospital, Shantou, China
| | - Raees Khan
- Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Pakistan
| | - Yilin Zheng
- Clinical Research Center, Shantou Central Hospital, Shantou, China
| | - Ping-Chin Lee
- Biotechnology Research Institute, Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia
- Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia
| | - Qingnan Li
- Clinical Research Center, Shantou Central Hospital, Shantou, China
- Department of Pharmacy, Shantou Central Hospital, Shantou, China
| | - Imran Khan
- Department of Biotechnology, Faculty of Chemical and Life Sciences, Abdul Wali Khan University Mardan, Mardan, Pakistan
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14
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Li SX, Guo Y. Gut microbiome: New perspectives for type 2 diabetes prevention and treatment. World J Clin Cases 2023; 11:7508-7520. [DOI: 10.12998/wjcc.v11.i31.7508] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 09/19/2023] [Accepted: 10/23/2023] [Indexed: 11/06/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM), which is distinguished by increased glucose levels in the bloodstream, is a metabolic disease with a rapidly increasing incidence worldwide. Nevertheless, the etiology and characteristics of the mechanism of T2DM remain unclear. Recently, abundant evidence has indicated that the intestinal microbiota is crucially involved in the initiation and progression of T2DM. The gut microbiome, the largest microecosystem, engages in material and energy metabolism in the human body. In this review, we concentrated on the correlation between the gut flora and T2DM. Meanwhile, we summarized the pathogenesis involving the intestinal flora in T2DM, as well as therapeutic approaches aimed at modulating the gut microbiota for the management of T2DM. Through the analysis presented here, we draw attention to further exploration of these research directions.
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Affiliation(s)
- Shu-Xiao Li
- School of Clinical Medicine, Changchun University of Traditional Chinese Medicine, Changchun 130000, Jilin Province, China
| | - Yan Guo
- School of Clinical Medicine, Changchun University of Traditional Chinese Medicine, Changchun 130000, Jilin Province, China
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15
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Carlsen H, Pajari AM. Dietary fiber - a scoping review for Nordic Nutrition Recommendations 2023. Food Nutr Res 2023; 67:9979. [PMID: 37920675 PMCID: PMC10619389 DOI: 10.29219/fnr.v67.9979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 08/27/2023] [Accepted: 08/30/2023] [Indexed: 11/04/2023] Open
Abstract
Dietary fiber is a term crudely defined as carbohydrates (CHOs) that escape digestion and uptake in the small intestine. Lignin, which is not a CHO, is also a part of the dietary fiber definition. Dietary fibers come in different sizes and forms, with a variety of combinations of monomeric units. Health authorities worldwide have for many years recommended a diet rich in dietary fibers based on consistent findings that dietary fibers are associated with reduced incidences of major non-communicable diseases, including obesity, type 2 diabetes, cardiovascular disease, and colorectal cancer. Most fibers come from common edible foods from the plant kingdom, but fibers are also found in food additives, supplements, and breast milk. The recommended intake in Nordic Nutrition Recommendations 2012 (NNR2012) is 25 g/d for women and 35 g/d for men, whereas the actual intake is significantly lower, ranging from 16 g/d to 22 g/d in women and 18 g/d to 26 g/d in men. New studies since NNR2012 confirm the current view that dietary fiber is beneficial for health, advocating intakes of at least 25 g/day.
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Affiliation(s)
- Harald Carlsen
- Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway
| | - Anne-Maria Pajari
- Department of Food and Nutrition, University of Helsinki, Helsinki, Finland
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16
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Barbosa EC, Bucar EEC, Jubé GR, Silveira LB, Silva NCD, Faria PCC, Ramos PLC, Moraes VRY, Barros JOB. Fecal microbiota transplantation and its repercussions in patients with melanoma refractory to anti-PD-1 therapy: scope review. Rev Col Bras Cir 2023; 50:e20233490. [PMID: 37222345 PMCID: PMC10508684 DOI: 10.1590/0100-6991e-20233490-en] [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: 10/24/2022] [Accepted: 02/24/2023] [Indexed: 05/25/2023] Open
Abstract
INTRODUCTION despite being extremely effective in some cases, up to 70% of patients with melanoma do not respond to anti-PD-1/PD-L1 (primary resistance) and many of the responders eventually progress (secondary resistance). Extensive efforts are being made to overcome this resistance through new strategies, especially aimed at modulating the intestinal microbiota. OBJECTIVE to assess whether fecal microbiota transplantation (FMT), associated with immunotherapy, is beneficial in the clinical course of patients with refractory melanoma. METHODS this is a scope review, based on studies collected on the MEDLINE, ScienceDirect, The Cochrane Library, Embase and BMJ Journals; using the terms: "Antibodies, Monoclonal"; "Drug Resistance, Neoplasm"; "Fecal Microbiota Transplantation"; "Host Microbial Interactions"; "Immunotherapy"; "Melanoma"; and "Microbiota". Clinical trials, in English, with relevant data on the subject and fully available were included. A cut-off period was not determined, due to the limited amount of evidence on the topic. RESULTS crossing the descriptors allowed the identification of 342 publications and, after applying the eligibility criteria, allowed the selection of 4 studies. From the analyses, it was observed that a considerable part of those studied overcame resistance to immune checkpoint inhibitors after FMT, with better response to treatment, less tumor growth and increased beneficial immune response. CONCLUSION it is noted that FMT favors the response of melanoma to immunotherapy, translated into significant clinical benefit. However, further studies are necessary for the complete elucidation of the bacteria and the mechanisms involved, as well as for the translation of new evidence to oncological care practice.
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Affiliation(s)
| | | | | | | | | | | | | | | | - João Ormindo Beltrão Barros
- - Universidade Evangélica de Goiás, Medicina - Anápolis - GO - Brasil
- - Hospital Santa Casa de Anápolis, Cancerologia Cirúrgica - Anápolis - GO - Brasil
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17
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Kurt F, Leventhal GE, Spalinger MR, Anthamatten L, Rogalla von Bieberstein P, Menzi C, Reichlin M, Meola M, Rosenthal F, Rogler G, Lacroix C, de Wouters T. Co-cultivation is a powerful approach to produce a robust functionally designed synthetic consortium as a live biotherapeutic product (LBP). Gut Microbes 2023; 15:2177486. [PMID: 36794804 PMCID: PMC9980632 DOI: 10.1080/19490976.2023.2177486] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 01/31/2023] [Indexed: 02/17/2023] Open
Abstract
The success of fecal microbiota transplants (FMT) has provided the necessary proof-of-concept for microbiome therapeutics. Yet, feces-based therapies have many associated risks and uncertainties, and hence defined microbial consortia that modify the microbiome in a targeted manner have emerged as a promising safer alternative to FMT. The development of such live biotherapeutic products has important challenges, including the selection of appropriate strains and the controlled production of the consortia at scale. Here, we report on an ecology- and biotechnology-based approach to microbial consortium construction that overcomes these issues. We selected nine strains that form a consortium to emulate the central metabolic pathways of carbohydrate fermentation in the healthy human gut microbiota. Continuous co-culturing of the bacteria produces a stable and reproducible consortium whose growth and metabolic activity are distinct from an equivalent mix of individually cultured strains. Further, we showed that our function-based consortium is as effective as FMT in counteracting dysbiosis in a dextran sodium sulfate mouse model of acute colitis, while an equivalent mix of strains failed to match FMT. Finally, we showed robustness and general applicability of our approach by designing and producing additional stable consortia of controlled composition. We propose that combining a bottom-up functional design with continuous co-cultivation is a powerful strategy to produce robust functionally designed synthetic consortia for therapeutic use.
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Affiliation(s)
- Fabienne Kurt
- PharmaBiome AG, Schlieren, Switzerland
- Laboratory of Food Biotechnology, Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland
| | | | - Marianne Rebecca Spalinger
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Laura Anthamatten
- PharmaBiome AG, Schlieren, Switzerland
- Laboratory of Food Biotechnology, Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland
| | | | | | | | | | | | - Gerhard Rogler
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Christophe Lacroix
- Laboratory of Food Biotechnology, Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland
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Guo XH, Zhu YL, Yang L, Li WJ, Du XF. The Effects of Multi-Donor Fecal Microbiota Transplantation Capsules Combined with Thalidomide on Hormone-Dependent Ulcerative Colitis. Infect Drug Resist 2022; 15:7495-7501. [PMID: 36570710 PMCID: PMC9784385 DOI: 10.2147/idr.s385485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 11/14/2022] [Indexed: 12/23/2022] Open
Abstract
Objective This study aimed to assess the effects of multi-donor fecal microbiota transplantation (FMT) capsules combined with thalidomide on hormone-dependent ulcerative colitis (UC). Methods A total of 59 patients with steroid-dependent UC treated at the Gastroenterology Department of the First Affiliated Hospital of Xinxiang Medical University between January 2017 and January 2019 were enrolled in this study. Using a random number table, the patients were divided into two groups: a group treated with FMT capsules (the FMT group) and a group treated with FMT capsules and thalidomide (the FMT+S group). Multi-donor FMT capsules were prepared, and all subjects and stool donors followed the FMT pathway for FMT transplantation. Each patient's Mayo score, C-reactive protein (CRP) level, and level of fecal calprotectin before FMT treatment and at week 1 and week 13 after treatment were recorded. All patients were followed up for 15 weeks. Results A total of 56.7% of the patients (34/59) achieved a therapeutic response at the end of the research period. Compared with the FMT group, the FMT+S group had better clinical benefit (P < 0.05). In the comparison of efficacy at week 1 and week 13 after treatment, the Mayo scores, calprotectin levels, and CRP indexes in the FMT+S group were better than those in the FMT group (P < 0.05). There were no serious adverse events in the treatment process or during follow-up. Conclusion A combination of FMT capsules and thalidomide provides a treatment choice for patients with hormone-dependent UC, and it can be used as an adjuvant therapy. However, large-scale, multi-center, and prospective trials are required to further verify the reliability of this treatment.
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Affiliation(s)
- Xiao-He Guo
- Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People’s Republic of China
| | - Yan-Li Zhu
- Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People’s Republic of China,Correspondence: Yan-Li Zhu, Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, No. 88 of Jiankang Road, Weihui District, Henan, 453100, People’s Republic of China, Tel +86 15036615840, Email
| | - Lu Yang
- Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People’s Republic of China
| | - Wen-Jing Li
- Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People’s Republic of China
| | - Xue-Fang Du
- Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People’s Republic of China
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Hyun J, Lee SK, Cheon JH, Yong DE, Koh H, Kang YK, Kim MH, Sohn Y, Cho Y, Baek YJ, Kim JH, Ahn JY, Jeong SJ, Yeom JS, Choi JY. Faecal microbiota transplantation reduces amounts of antibiotic resistance genes in patients with multidrug-resistant organisms. Antimicrob Resist Infect Control 2022; 11:20. [PMID: 35093183 PMCID: PMC8800327 DOI: 10.1186/s13756-022-01064-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 01/18/2022] [Indexed: 12/04/2022] Open
Abstract
Background Multidrug-resistant organisms (MDROs) such as vancomycin-resistant enterococci (VRE) and carbapenemase-producing Enterobacteriaceae (CPE) are associated with prolonged hospitalisation, increased medical costs, and severe infections. Faecal microbiota transplantation (FMT) has emerged as an important strategy for decolonisation. This study aimed to evaluate the genetic response of MDROs to FMT. Methods A single-centre prospective study was conducted on patients infected with VRE, CPE, or VRE/CPE who underwent FMT between May 2018 and April 2019. Genetic response was assessed as the change in the expression of the resistance genes VanA, blaKPC, blaNDM, and blaOXA on days 1, 7, 14, and 28 by real-time reverse-transcription polymerase chain reaction. Results Twenty-nine patients received FMT, of which 26 (59.3%) were infected with VRE, 5 (11.1%) with CPE, and 8 (29.6%) with VRE/CPE. The mean duration of MDRO carriage before FMT was 71 days. Seventeen patients (63.0%) used antibiotics within a week of FMT. In a culture-dependent method, the expression of VanA and overall genes significantly decreased (p = 0.011 and p = 0.003 respectively). In a culture-independent method, VanA, blaNDM, and overall gene expression significantly decreased over time after FMT (p = 0.047, p = 0.048, p = 0.002, respectively). Similar results were confirmed following comparison between each time point in both the culture-dependent and -independent methods. Regression analysis did not reveal important factors underlying the genetic response after FMT. No adverse events were observed. Conclusion FMT in patients infected with MDROs downregulates the expression of resistance genes, especially VanA, and facilitates MDRO decolonisation.
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Wei S, Jespersen ML, Baunwall SMD, Myers PN, Smith EM, Dahlerup JF, Rasmussen S, Nielsen HB, Licht TR, Bahl MI, Hvas CL. Cross-generational bacterial strain transfer to an infant after fecal microbiota transplantation to a pregnant patient: a case report. MICROBIOME 2022; 10:193. [PMID: 36352460 PMCID: PMC9647999 DOI: 10.1186/s40168-022-01394-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 10/13/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) effectively prevents the recurrence of Clostridioides difficile infection (CDI). Long-term engraftment of donor-specific microbial consortia may occur in the recipient, but potential further transfer to other sites, including the vertical transmission of donor-specific strains to future generations, has not been investigated. Here, we report, for the first time, the cross-generational transmission of specific bacterial strains from an FMT donor to a pregnant patient with CDI and further to her child, born at term, 26 weeks after the FMT treatment. METHODS A pregnant woman (gestation week 12 + 5) with CDI was treated with FMT via colonoscopy. She gave vaginal birth at term to a healthy baby. Fecal samples were collected from the feces donor, the mother (before FMT, and 1, 8, 15, 22, 26, and 50 weeks after FMT), and the infant (meconium at birth and 3 and 6 months after birth). Fecal samples were profiled by deep metagenomic sequencing for strain-level analysis. The microbial transfer was monitored using single nucleotide variants in metagenomes and further compared to a collection of metagenomic samples from 651 healthy infants and 58 healthy adults. RESULTS The single FMT procedure led to an uneventful and sustained clinical resolution in the patient, who experienced no further CDI-related symptoms up to 50 weeks after treatment. The gut microbiota of the patient with CDI differed considerably from the healthy donor and was characterized as low in alpha diversity and enriched for several potential pathogens. The FMT successfully normalized the patient's gut microbiota, likely by donor microbiota transfer and engraftment. Importantly, our analysis revealed that some specific strains were transferred from the donor to the patient and then further to the infant, thus demonstrating cross-generational microbial transfer. CONCLUSIONS The evidence for cross-generational strain transfer following FMT provides novel insights into the dynamics and engraftment of bacterial strains from healthy donors. The data suggests FMT treatment of pregnant women as a potential strategy to introduce beneficial strains or even bacterial consortia to infants, i.e., neonatal seeding. Video Abstract.
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Affiliation(s)
- Shaodong Wei
- National Food Institute, Technical University of Denmark, Kemitorvet 202, 2800, Kgs Lyngby, Denmark
| | - Marie Louise Jespersen
- National Food Institute, Technical University of Denmark, Kemitorvet 202, 2800, Kgs Lyngby, Denmark
- Clinical-Microbiomics A/S, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Simon Mark Dahl Baunwall
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | | | - Emilie Milton Smith
- National Food Institute, Technical University of Denmark, Kemitorvet 202, 2800, Kgs Lyngby, Denmark
| | - Jens Frederik Dahlerup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Simon Rasmussen
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | - Tine Rask Licht
- National Food Institute, Technical University of Denmark, Kemitorvet 202, 2800, Kgs Lyngby, Denmark
| | - Martin Iain Bahl
- National Food Institute, Technical University of Denmark, Kemitorvet 202, 2800, Kgs Lyngby, Denmark.
| | - Christian Lodberg Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
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21
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Singh T, Bedi P, Bumrah K, Gandhi D, Arora T, Verma N, Schleicher M, Rai MP, Garg R, Verma B, Sanaka MR. Fecal Microbiota Transplantation and Medical Therapy for Clostridium difficile Infection : Meta-analysis of Randomized Controlled Trials. J Clin Gastroenterol 2022; 56:881-888. [PMID: 34516460 DOI: 10.1097/mcg.0000000000001610] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 07/29/2021] [Indexed: 12/13/2022]
Abstract
GOALS The aim was to assess the effectiveness of fecal microbiota transplantation (FMT) against medical therapy (MT). BACKGROUND FMT has shown good outcomes in the treatment of Clostridium difficile infection (CDI). We aimed to conduct a systematic review and meta-analysis to compare the effectiveness of FMT versus MT for CDI. STUDY We performed a comprehensive search to identify randomized controlled trials comparing FMT against MT in patients with CDI. Outcomes of interest were clinical cure as determined by the resolution of diarrhea and/or negative C. difficile testing. Primary CDI is defined as the first episode of CDI confirmed endoscopically or by laboratory analysis. Recurrent C. difficile infection (RCDI) is defined as laboratory or endoscopically confirmed episode of CDI after at least 1 course of approved antibiotic regimen. RESULTS A total of 7 studies with 238 patients were included in meta-analysis. Compared with MT, FMT did not have a statistically significant difference for clinical cure of combined primary and RCDI after first session [risk ratio (RR): 1.52, 95% confidence interval (CI): 0.90, 2.58; P =0.12; I2 =77%] and multiple sessions of FMT (RR: 1.68; CI: 0.96, 2.94; P =0.07; I2 =82%). On subgroup analysis, FMT has statistically higher rate of response than MT (RR: 2.41; CI: 1.20, 4.83; I2 =78%) for RCDI. However, for primary CDI there is no statistically significant difference between FMT and MT (RR: 1.00; CI: 0.72, 1.39; I2 =0%). CONCLUSION As per our analysis, FMT should not be utilized for every patient with CDI. It is more effective in RCDI, but the results were not significant in patients with primary CDI.
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Affiliation(s)
| | | | | | - Darshan Gandhi
- Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Tanureet Arora
- Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Nikita Verma
- Baba Farid University of Health Sciences, Faridkot, Punjab, India
| | | | - Manoj P Rai
- Department of Medicine, Asante Rogue Regional Medical Center, Medford, OR
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22
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Biazzo M, Allegra M, Deidda G. Clostridioides difficile and neurological disorders: New perspectives. Front Neurosci 2022; 16:946601. [PMID: 36203814 PMCID: PMC9530032 DOI: 10.3389/fnins.2022.946601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 08/24/2022] [Indexed: 12/02/2022] Open
Abstract
Despite brain physiological functions or pathological dysfunctions relying on the activity of neuronal/non-neuronal populations, over the last decades a plethora of evidence unraveled the essential contribution of the microbial populations living and residing within the gut, called gut microbiota. The gut microbiota plays a role in brain (dys)functions, and it will become a promising valuable therapeutic target for several brain pathologies. In the present mini-review, after a brief overview of the role of gut microbiota in normal brain physiology and pathology, we focus on the role of the bacterium Clostridioides difficile, a pathogen responsible for recurrent and refractory infections, in people with neurological diseases, summarizing recent correlative and causative evidence in the scientific literature and highlighting the potential of microbiota-based strategies targeting this pathogen to ameliorate not only gastrointestinal but also the neurological symptoms.
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Affiliation(s)
- Manuele Biazzo
- The BioArte Limited, Life Sciences Park, San Gwann, Malta
- SienabioACTIVE, University of Siena, Siena, Italy
| | - Manuela Allegra
- Neuroscience Institute, National Research Council (IN-CNR), Padua, Italy
| | - Gabriele Deidda
- Department of Biomedical Sciences, University of Padua, Padua, Italy
- *Correspondence: Gabriele Deidda
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23
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Drivers and determinants of strain dynamics following fecal microbiota transplantation. Nat Med 2022; 28:1902-1912. [PMID: 36109636 PMCID: PMC9499871 DOI: 10.1038/s41591-022-01913-0] [Citation(s) in RCA: 99] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 06/23/2022] [Indexed: 02/06/2023]
Abstract
AbstractFecal microbiota transplantation (FMT) is a therapeutic intervention for inflammatory diseases of the gastrointestinal tract, but its clinical mode of action and subsequent microbiome dynamics remain poorly understood. Here we analyzed metagenomes from 316 FMTs, sampled pre and post intervention, for the treatment of ten different disease indications. We quantified strain-level dynamics of 1,089 microbial species, complemented by 47,548 newly constructed metagenome-assembled genomes. Donor strain colonization and recipient strain resilience were mostly independent of clinical outcomes, but accurately predictable using LASSO-regularized regression models that accounted for host, microbiome and procedural variables. Recipient factors and donor–recipient complementarity, encompassing entire microbial communities to individual strains, were the main determinants of strain population dynamics, providing insights into the underlying processes that shape the post-FMT gut microbiome. Applying an ecology-based framework to our findings indicated parameters that may inform the development of more effective, targeted microbiome therapies in the future, and suggested how patient stratification can be used to enhance donor microbiota colonization or the displacement of recipient microbes in clinical practice.
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24
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Soveral LF, Korczaguin GG, Schmidt PS, Nunes IS, Fernandes C, Zárate-Bladés CR. Immunological mechanisms of fecal microbiota transplantation in recurrent Clostridioides difficile infection. World J Gastroenterol 2022; 28:4762-4772. [PMID: 36156924 PMCID: PMC9476857 DOI: 10.3748/wjg.v28.i33.4762] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 05/06/2022] [Accepted: 08/16/2022] [Indexed: 02/06/2023] Open
Abstract
Fecal microbiota transplantation (FMT) is a successful method for treating recurrent Clostridioides difficile (C. difficile) infection (rCDI) with around 90% efficacy. Due to the relative simplicity of this approach, it is being widely used and currently, thousands of patients have been treated with FMT worldwide. Nonetheless, the mechanisms underlying its effects are just beginning to be understood. Data indicate that FMT effectiveness is due to a combination of microbiological direct mechanisms against C. difficile, but also through indirect mechanisms including the production of microbiota-derived metabolites as secondary bile acids and short chain fatty acids. Moreover, the modulation of the strong inflammatory response triggered by C. difficile after FMT seems to rely on a pivotal role of regulatory T cells, which would be responsible for the reduction of several cells and soluble inflammatory mediators, ensuing normalization of the intestinal mucosal immune system. In this minireview, we analyze recent advances in these immunological aspects associated with the efficacy of FMT.
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Affiliation(s)
- Lucas F Soveral
- Laboratory of Immunoregulation, Department of Microbiology, Immunology, and Parasitology, Center for Dysbiosis Control, Federal University of Santa Catarina, Florianopolis 88037-000, Brazil
| | - Gabriela G Korczaguin
- Laboratory of Immunoregulation, Department of Microbiology, Immunology, and Parasitology, Center for Dysbiosis Control, Federal University of Santa Catarina, Florianopolis 88037-000, Brazil
| | - Pedro S Schmidt
- Laboratory of Immunoregulation, Department of Microbiology, Immunology, and Parasitology, Center for Dysbiosis Control, Federal University of Santa Catarina, Florianopolis 88037-000, Brazil
| | - Isabel S Nunes
- Laboratory of Immunoregulation, Department of Microbiology, Immunology, and Parasitology, Center for Dysbiosis Control, Federal University of Santa Catarina, Florianopolis 88037-000, Brazil
| | - Camilo Fernandes
- Laboratory of Immunoregulation, Department of Microbiology, Immunology, and Parasitology, Center for Dysbiosis Control, Federal University of Santa Catarina, Florianopolis 88037-000, Brazil
- Division of Infectious Diseases, Hospital Nereu Ramos, Florianopolis 88025-301, Brazil
| | - Carlos R Zárate-Bladés
- Laboratory of Immunoregulation, Department of Microbiology, Immunology, and Parasitology, Center for Dysbiosis Control, Federal University of Santa Catarina, Florianopolis 88037-000, Brazil
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25
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Biazzo M, Deidda G. Fecal Microbiota Transplantation as New Therapeutic Avenue for Human Diseases. J Clin Med 2022; 11:jcm11144119. [PMID: 35887883 PMCID: PMC9320118 DOI: 10.3390/jcm11144119] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/08/2022] [Accepted: 07/12/2022] [Indexed: 02/01/2023] Open
Abstract
The human body is home to a variety of micro-organisms. Most of these microbial communities reside in the gut and are referred to as gut microbiota. Over the last decades, compelling evidence showed that a number of human pathologies are associated with microbiota dysbiosis, thereby suggesting that the reinstatement of physiological microflora balance and composition might ameliorate the clinical symptoms. Among possible microbiota-targeted interventions, pre/pro-biotics supplementations were shown to provide effective results, but the main limitation remains in the limited microbial species available as probiotics. Differently, fecal microbiota transplantation involves the transplantation of a solution of fecal matter from a donor into the intestinal tract of a recipient in order to directly change the recipient's gut microbial composition aiming to confer a health benefit. Firstly used in the 4th century in traditional Chinese medicine, nowadays, it has been exploited so far to treat recurrent Clostridioides difficile infections, but accumulating data coming from a number of clinical trials clearly indicate that fecal microbiota transplantation may also carry the therapeutic potential for a number of other conditions ranging from gastrointestinal to liver diseases, from cancer to inflammatory, infectious, autoimmune diseases and brain disorders, obesity, and metabolic syndrome. In this review, we will summarize the commonly used preparation and delivery methods, comprehensively review the evidence obtained in clinical trials in different human conditions and discuss the variability in the results and the pivotal importance of donor selection. The final aim is to stimulate discussion and open new therapeutic perspectives among experts in the use of fecal microbiota transplantation not only in Clostridioides difficile infection but as one of the first strategies to be used to ameliorate a number of human conditions.
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Affiliation(s)
- Manuele Biazzo
- The BioArte Limited, Life Sciences Park, Triq San Giljan, SGN 3000 San Gwann, Malta;
- SienabioACTIVE, University of Siena, Via Aldo Moro 1, 53100 Siena, Italy
| | - Gabriele Deidda
- Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, Italy
- Correspondence: ; Tel.: +39-049-827-6125
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26
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Doroftei B, Ilie OD, Diaconu R, Hutanu D, Stoian I, Ilea C. An Updated Narrative Mini-Review on the Microbiota Changes in Antenatal and Post-Partum Depression. Diagnostics (Basel) 2022; 12:diagnostics12071576. [PMID: 35885482 PMCID: PMC9315700 DOI: 10.3390/diagnostics12071576] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 06/26/2022] [Accepted: 06/27/2022] [Indexed: 12/02/2022] Open
Abstract
Background: Antenatal depression (AND) and post-partum depression (PPD) are long-term debilitating psychiatric disorders that significantly influence the composition of the gut flora of mothers and infants that starts from the intrauterine life. Not only does bacterial ratio shift impact the immune system, but it also increases the risk of potentially life-threatening disorders. Material and Methods: Therefore, we conducted a narrative mini-review aiming to gather all evidence published between 2018–2022 regarding microflora changes in all three stages of pregnancy. Results: We initially identified 47 potentially eligible studies, from which only 7 strictly report translocations; 3 were conducted on rodent models and 4 on human patients. The remaining studies were divided based on their topic, precisely focused on how probiotics, breastfeeding, diet, antidepressants, exogenous stressors, and plant-derived compounds modulate in a bidirectional way upon behavior and microbiota. Almost imperatively, dysbacteriosis cause cognitive impairments, reflected by abnormal temperament and personality traits that last up until 2 years old. Thankfully, a distinct technique that involves fecal matter transfer between individuals has been perfected over the years and was successfully translated into clinical practice. It proved to be a reliable approach in diminishing functional non- and gastrointestinal deficiencies, but a clear link between depressive women’s gastrointestinal/vaginal microbiota and clinical outcomes following reproductive procedures is yet to be established. Another gut-dysbiosis-driving factor is antibiotics, known for their potential to trigger inflammation. Fortunately, the studies conducted on mice that lack microbiota offer, without a shadow of a doubt, insight. Conclusions: It can be concluded that the microbiota is a powerful organ, and its optimum functionality is crucial, likely being the missing puzzle piece in the etiopathogenesis of psychiatric disorders.
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Affiliation(s)
- Bogdan Doroftei
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, No. 16, 700115 Iasi, Romania; (B.D.); (I.S.); (C.I.)
- Clinical Hospital of Obstetrics and Gynecology “Cuza Voda”, Cuza Voda Street, No. 34, 700038 Iasi, Romania;
- Origyn Fertility Center, Palace Street, No. 3C, 700032 Iasi, Romania
| | - Ovidiu-Dumitru Ilie
- Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University, Carol I Avenue, No. 20A, 700505 Iasi, Romania
- Correspondence:
| | - Roxana Diaconu
- Clinical Hospital of Obstetrics and Gynecology “Cuza Voda”, Cuza Voda Street, No. 34, 700038 Iasi, Romania;
- Origyn Fertility Center, Palace Street, No. 3C, 700032 Iasi, Romania
| | - Delia Hutanu
- Department of Biology, Faculty of Chemistry-Biology-Geography, West University of Timisoara, Vasile Pârvan Avenue, No. 4, 300115 Timisoara, Romania;
| | - Irina Stoian
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, No. 16, 700115 Iasi, Romania; (B.D.); (I.S.); (C.I.)
| | - Ciprian Ilea
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, No. 16, 700115 Iasi, Romania; (B.D.); (I.S.); (C.I.)
- Clinical Hospital of Obstetrics and Gynecology “Cuza Voda”, Cuza Voda Street, No. 34, 700038 Iasi, Romania;
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27
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Dash S, Syed YA, Khan MR. Understanding the Role of the Gut Microbiome in Brain Development and Its Association With Neurodevelopmental Psychiatric Disorders. Front Cell Dev Biol 2022; 10:880544. [PMID: 35493075 PMCID: PMC9048050 DOI: 10.3389/fcell.2022.880544] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 03/28/2022] [Indexed: 12/12/2022] Open
Abstract
The gut microbiome has a tremendous influence on human physiology, including the nervous system. During fetal development, the initial colonization of the microbiome coincides with the development of the nervous system in a timely, coordinated manner. Emerging studies suggest an active involvement of the microbiome and its metabolic by-products in regulating early brain development. However, any disruption during this early developmental process can negatively impact brain functionality, leading to a range of neurodevelopment and neuropsychiatric disorders (NPD). In this review, we summarize recent evidence as to how the gut microbiome can influence the process of early human brain development and its association with major neurodevelopmental psychiatric disorders such as autism spectrum disorders, attention-deficit hyperactivity disorder, and schizophrenia. Further, we discuss how gut microbiome alterations can also play a role in inducing drug resistance in the affected individuals. We propose a model that establishes a direct link of microbiome dysbiosis with the exacerbated inflammatory state, leading to functional brain deficits associated with NPD. Based on the existing research, we discuss a framework whereby early diet intervention can boost mental wellness in the affected subjects and call for further research for a better understanding of mechanisms that govern the gut-brain axis may lead to novel approaches to the study of the pathophysiology and treatment of neuropsychiatric disorders.
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Affiliation(s)
- Somarani Dash
- Life Sciences Division, Institute of Advanced Study in Science and Technology (IASST), Guwahati, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Yasir Ahmed Syed
- School of Biosciences and Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Cardiff, United Kingdom
| | - Mojibur R. Khan
- Life Sciences Division, Institute of Advanced Study in Science and Technology (IASST), Guwahati, India
- *Correspondence: Mojibur R. Khan,
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28
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Donor Screening Revisions of Fecal Microbiota Transplantation in Patients with Ulcerative Colitis. J Clin Med 2022; 11:jcm11041055. [PMID: 35207328 PMCID: PMC8879222 DOI: 10.3390/jcm11041055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 02/14/2022] [Accepted: 02/16/2022] [Indexed: 11/26/2022] Open
Abstract
Fecal microbiota transplantation (FMT) has been recognized as a promising treatment for dysbiosis-related diseases. Since 2014, FMT has been utilized to treat ulcerative colitis (UC) in our clinical studies and has shown efficacy and safety. As donor screening (DS) is the primary step to ensure the safety of FMT, we report our experience with DS and present the screening results to improve the prospective DS criteria and provide references for future studies. The donor candidates were screened according to the DS criteria. The first DS criteria were proposed in June 2014 and revised substantially in May 2018. We further sorted the screening results and costs of laboratory tests. From June 2014 to April 2018, the DS eligibility rate was 50%. The total laboratory testing cost for each candidate was JPY 17,580/USD 160.21. From May 2018 to September 2021, the DS eligibility rate was 25.6%. The total laboratory testing cost for each candidate was JPY 40,740/USD 371.36. The reduction in donor eligibility rates due to more stringent criteria should be considered for cost and safety. Studies must consider the latest updates and make timely modifications in the DS criteria to ensure patient safety.
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29
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Takeuchi H, Yoshikane Y, Takenaka H, Kimura A, Islam JM, Matsuda R, Okamoto A, Hashimoto Y, Yano R, Yamaguchi K, Sato S, Ishizuka S. Health Effects of Drinking Water Produced from Deep Sea Water: A Randomized Double-Blind Controlled Trial. Nutrients 2022; 14:nu14030581. [PMID: 35276942 PMCID: PMC8839038 DOI: 10.3390/nu14030581] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 01/15/2022] [Accepted: 01/20/2022] [Indexed: 02/05/2023] Open
Abstract
Global trends focus on a balanced intake of foods and beverages to maintain health. Drinking water (MIU; hardness = 88) produced from deep sea water (DSW) collected offshore of Muroto, Japan, is considered healthy. We previously reported that the DSW-based drinking water (RDSW; hardness = 1000) improved human gut health. The aim of this randomized double-blind controlled trial was to assess the effects of MIU on human health. Volunteers were assigned to MIU (n = 41) or mineral water (control) groups (n = 41). Participants consumed 1 L of either water type daily for 12 weeks. A self-administered questionnaire was administered, and stool and urine samples were collected throughout the intervention. We measured the fecal biomarkers of nine short-chain fatty acids (SCFAs) and secretory immunoglobulin A (sIgA), as well as urinary isoflavones. In the MIU group, concentrations of three major SCFAs and sIgA increased postintervention. MIU intake significantly affected one SCFA (butyric acid). The metabolic efficiency of daidzein-to-equol conversion was significantly higher in the MIU group than in the control group throughout the intervention. MIU intake reflected the intestinal environment through increased production of three major SCFAs and sIgA, and accelerated daidzein-to-equol metabolic conversion, suggesting the beneficial health effects of MIU.
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Affiliation(s)
- Hiroaki Takeuchi
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, 4-3 Kouzunomori, Narita-City 286-8686, Chiba, Japan; (A.K.); (J.M.I.); (R.M.); (A.O.); (Y.H.); (R.Y.); (K.Y.); (S.S.)
- Correspondence: ; Tel.: +81-476-20-7762
| | - Yu Yoshikane
- Department of Human Living Sciences, Notre Dame Seishin University, 2-16-9 Ifuku-cho, Kita-ku, Okayama-city 700-8516, Okayama, Japan;
| | - Hirotsugu Takenaka
- DyDo-T Beverage Co. Ltd., 1310-1 Hanechou-ko, Muroto-City 781-6741, Kochi, Japan;
| | - Asako Kimura
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, 4-3 Kouzunomori, Narita-City 286-8686, Chiba, Japan; (A.K.); (J.M.I.); (R.M.); (A.O.); (Y.H.); (R.Y.); (K.Y.); (S.S.)
| | - Jahirul Md. Islam
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, 4-3 Kouzunomori, Narita-City 286-8686, Chiba, Japan; (A.K.); (J.M.I.); (R.M.); (A.O.); (Y.H.); (R.Y.); (K.Y.); (S.S.)
| | - Reimi Matsuda
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, 4-3 Kouzunomori, Narita-City 286-8686, Chiba, Japan; (A.K.); (J.M.I.); (R.M.); (A.O.); (Y.H.); (R.Y.); (K.Y.); (S.S.)
| | - Aoi Okamoto
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, 4-3 Kouzunomori, Narita-City 286-8686, Chiba, Japan; (A.K.); (J.M.I.); (R.M.); (A.O.); (Y.H.); (R.Y.); (K.Y.); (S.S.)
| | - Yusuke Hashimoto
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, 4-3 Kouzunomori, Narita-City 286-8686, Chiba, Japan; (A.K.); (J.M.I.); (R.M.); (A.O.); (Y.H.); (R.Y.); (K.Y.); (S.S.)
| | - Rie Yano
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, 4-3 Kouzunomori, Narita-City 286-8686, Chiba, Japan; (A.K.); (J.M.I.); (R.M.); (A.O.); (Y.H.); (R.Y.); (K.Y.); (S.S.)
| | - Koichi Yamaguchi
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, 4-3 Kouzunomori, Narita-City 286-8686, Chiba, Japan; (A.K.); (J.M.I.); (R.M.); (A.O.); (Y.H.); (R.Y.); (K.Y.); (S.S.)
| | - Shouichi Sato
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, 4-3 Kouzunomori, Narita-City 286-8686, Chiba, Japan; (A.K.); (J.M.I.); (R.M.); (A.O.); (Y.H.); (R.Y.); (K.Y.); (S.S.)
| | - Satoshi Ishizuka
- Center for Regional Sustainability and Innovation, Kochi University, 2-17-47 Asakurahonmachi, Kochi-City 780-8073, Kochi, Japan;
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30
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Alharthi A, Alhazmi S, Alburae N, Bahieldin A. The Human Gut Microbiome as a Potential Factor in Autism Spectrum Disorder. Int J Mol Sci 2022; 23:ijms23031363. [PMID: 35163286 PMCID: PMC8835713 DOI: 10.3390/ijms23031363] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 01/18/2022] [Accepted: 01/24/2022] [Indexed: 11/16/2022] Open
Abstract
The high prevalence of gastrointestinal (GI) disorders among autism spectrum disorder (ASD) patients has prompted scientists to look into the gut microbiota as a putative trigger in ASD pathogenesis. Thus, many studies have linked the gut microbial dysbiosis that is frequently observed in ASD patients with the modulation of brain function and social behavior, but little is known about this connection and its contribution to the etiology of ASD. This present review highlights the potential role of the microbiota–gut–brain axis in autism. In particular, it focuses on how gut microbiota dysbiosis may impact gut permeability, immune function, and the microbial metabolites in autistic people. We further discuss recent findings supporting the possible role of the gut microbiome in initiating epigenetic modifications and consider the potential role of this pathway in influencing the severity of ASD. Lastly, we summarize recent updates in microbiota-targeted therapies such as probiotics, prebiotics, dietary supplements, fecal microbiota transplantation, and microbiota transfer therapy. The findings of this paper reveal new insights into possible therapeutic interventions that may be used to reduce and cure ASD-related symptoms. However, well-designed research studies using large sample sizes are still required in this area of study.
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Affiliation(s)
- Amani Alharthi
- Department of Biology, Faculty of Science, Majmaah University, Al Zulfi 11932, Saudi Arabia
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (S.A.); (N.A.)
- Correspondence: (A.A.); (A.B.)
| | - Safiah Alhazmi
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (S.A.); (N.A.)
| | - Najla Alburae
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (S.A.); (N.A.)
| | - Ahmed Bahieldin
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (S.A.); (N.A.)
- Correspondence: (A.A.); (A.B.)
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31
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Servetas SL, Daschner PJ, Guyard C, Thomas V, Affagard H, Sergaki C, Sokol H, Wargo JA, Wu GD, Sabot P. Evolution of FMT – From early clinical to standardized treatments. Biologicals 2022; 76:31-35. [DOI: 10.1016/j.biologicals.2022.01.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 01/09/2022] [Accepted: 01/10/2022] [Indexed: 01/22/2023] Open
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32
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Elhusein AM, Fadlalmola HA. Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome Patients: An Updated Systematic Review and Meta-Analysis. Gastroenterol Nurs 2022; 45:11-20. [PMID: 35108241 DOI: 10.1097/sga.0000000000000652] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 10/13/2021] [Indexed: 12/16/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic gastrointestinal disease characterized by abdominal discomfort and bloating, diarrhea, and/or constipation. Fecal microbiota transplantation (FMT) is transferring the fecal bacteria and other microorganisms from a healthy person to another. We performed this systematic review and meta-analysis to assess the efficacy of FMT in treating IBS patients. We searched Scopus, PubMed, Cochrane, and Web of Science databases through June 2021 using relevant key words. We included 19 studies. Fecal microbiota transplantation was significantly superior to placebo in IBS quality of life after 4 weeks (mean difference [MD] = 7.47, 95% confidence interval [CI]: 2.05-12.89, p = .04), 12 weeks (MD = 9.99, 95% CI: 5.78-14.19, p < .00001), and 24 weeks (MD = 8.49, 95% CI: 0.47-16.52, p = .04), with no difference regarding IBS improvement symptoms and the IBS Severity Scoring System (SSS). Single-arm analysis revealed that the incidence of improvement of IBS symptoms was 57.8% (45.6%-69.9%) with reduction in IBS-SSS (MD = -74, 95% CI: -101.7 to -46.3). Fecal microbiota transplantation was superior to placebo in improving quality of life after 4, 12, and 24 weeks. Also, FMT improved IBS symptoms and reduced the IBS-SSS score. However, no deference was detected between FMT and placebo in IBS-SSS score and IBS symptoms improvement.
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Affiliation(s)
- Amal Mohamed Elhusein
- Amal Mohamed Elhusein, PhD, RN, MCH , is Assistant Professor, College of Applied Medical Science, Nursing Department, Bisha University, Bisha, Saudi Arabia; and Assistant Professor, Faculty of Nursing, Khartoum University, Khartoum, Sudan
- Hammad Ali Fadlalmola, PhD, RN, CHN , is Associate Professor, Department of Community Health Nursing, Taibah University, Nursing College, Almadinah, Saudi Arabia
| | - Hammad Ali Fadlalmola
- Amal Mohamed Elhusein, PhD, RN, MCH , is Assistant Professor, College of Applied Medical Science, Nursing Department, Bisha University, Bisha, Saudi Arabia; and Assistant Professor, Faculty of Nursing, Khartoum University, Khartoum, Sudan
- Hammad Ali Fadlalmola, PhD, RN, CHN , is Associate Professor, Department of Community Health Nursing, Taibah University, Nursing College, Almadinah, Saudi Arabia
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Shah F, Dwivedi M. Pathophysiological Role of Gut Microbiota Affecting Gut–Brain Axis and Intervention of Probiotics and Prebiotics in Autism Spectrum Disorder. PROBIOTIC RESEARCH IN THERAPEUTICS 2022:69-115. [DOI: 10.1007/978-981-16-6760-2_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Ji Y, Tao T, Zhang J, Su A, Zhao L, Chen H, Hu Q. Comparison of effects on colitis-associated tumorigenesis and gut microbiota in mice between Ophiocordyceps sinensis and Cordyceps militaris. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 90:153653. [PMID: 34330600 DOI: 10.1016/j.phymed.2021.153653] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 06/23/2021] [Accepted: 07/02/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Gut microbiota plays an indispensable role in the treatment of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). As traditional medicinal fungi, previous studies have shown that Ophiocordyceps sinensis could better maintain intestinal health via promoting the growth of probiotics in vitro compared with Cordyceps militaris. However, the detailed pharmacological activities and clinical efficacy of O. sinensis and C. militaris are still elusive. PURPOSE We aimed to evaluate the different actions of O. sinensis and C. militaris on colitis-associated tumorigenesis in Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS)-treated mice and explore the potential gut microbiota-dependent mechanisms. METHODS C57BL/6 mice (Male, 4 weeks old) were used to construct the AOM/DSS-induced CAC mice model. The mice were administered with 0.6 mg/g/d O. sinensis or C. militaris for 12 weeks. It's worth noting that fecal microbiota transplantation (FMT) and antibiotic treatment were used to investigated the complex interactions between the medicinal fungi, gut microbiota and colonic tumorigenesis. RESULTS O. sinensis treatment significantly increased the body weight and survival rate, reduced the number of colon tumors, improved the damage of colon epithelial tissue, restored the crypt structure and alleviate the colonic inflammation in AOM/DSS-treated mice. RT-qPCR results indicated that O. sinensis partly regulated the Wnt/β-catenin signaling via alleviating the overexpression of β-catenin, TCF4 and c-Myc genes in adjacent noncancerous tissues. Compared with C. militaris, O. sinensis showed better anti-tumor activity. Gut microbiota analysis revealed that O. sinensis reversed the decline of gut microbiota diversity and the structural disorder induced by AOM/DSS. Spearman's correlation analysis showed that O. sinensis promoted the growth of Parabacteroides goldsteinii and Bifidobacterium pseudolongum PV8-2, which were positively correlated with the anti-tumor activity and the production of SCFAs. FMT combined with antibiotic treatment showed that horizontal fecal transfer derived from O. sinensis-treated mice improved the intestinal inflammation and alleviated the colitis-associated tumorigenesis, which was consistent with the direct ingestion of O. sinensis. CONCLUSION O. sinensis could better attenuate colitis-associated tumorigenesis compared with C. militaris. These effects might be at least partially due to the increased abundance of probiotics, especially P. goldsteinii and B. pseudolongum PV8-2.
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Affiliation(s)
- Yang Ji
- College of Food Science and Engineering, Nanjing University of Finance and Economics, Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China
| | - Tianyi Tao
- College of Food Science and Engineering, Nanjing University of Finance and Economics, Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China
| | - Junmiao Zhang
- College of Food Science and Engineering, Nanjing University of Finance and Economics, Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China
| | - Anxiang Su
- College of Food Science and Engineering, Nanjing University of Finance and Economics, Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China
| | - Liyan Zhao
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Hui Chen
- Jiangsu Alphay Bio-technology Co., Ltd., Nantong 226009, China
| | - Qiuhui Hu
- College of Food Science and Engineering, Nanjing University of Finance and Economics, Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China.
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Zhu F, Ke Y, Luo Y, Wu J, Wu P, Ma F, Liu Y. Effects of Different Treatment of Fecal Microbiota Transplantation Techniques on Treatment of Ulcerative Colitis in Rats. Front Microbiol 2021; 12:683234. [PMID: 34335508 PMCID: PMC8317227 DOI: 10.3389/fmicb.2021.683234] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Accepted: 06/11/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease with abdominal pain, mucus, pus and blood in the stool as the main clinical manifestations. The pathogenesis of UC is still not completely clear, and multiple factors, such as genetic susceptibility, immune response, intestinal microecological changes and environmental factors, together lead to the onset of UC. In recent years, the role of intestinal microbiota disturbances on the pathogenesis of UC has received widespread attention. Therefore, fecal microbiota transplantation (FMT), which changes the intestinal microecological environment of UC patients by transplantation of normal fecal bacteria, has attracted increasing attention from researchers. However, there are no guidelines to recommend fresh FMT or frozen FMT in the treatment of UC, and there are few studies on this. Therefore, the purpose of this study was to explore the effects of fresh and frozen FMT methods on the treatment of experimental UC models in rats. Results: Compared with the model control group, all FMT groups achieved better efficacy, mainly manifested as weight gain by the rats, improvements in fecal characteristics and blood stools, reduced inflammatory factors and normal bacterial microbiota. The efficacy of the frozen FMT group was better than that of the fresh FMT group in terms of behavior and colon length. Conclusion: FMT method supplements the gut microbiota with beneficial bacteria, such as short-chain fatty acid-producing bacteria. These bacteria can regulate intestinal function, protect the mucosal barrier and reduce harmful bacteria, thus mitigating the damage to the intestinal barrier and the associated inflammatory response, resulting in UC remission. FMT is a feasible method for treating UC, with frozen FMT having a superior therapeutic effect than that of fresh FMT.
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Affiliation(s)
- Fangyuan Zhu
- The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yifan Ke
- The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yiting Luo
- The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jiaqian Wu
- The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Pei Wu
- The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Fangxiao Ma
- The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yingchao Liu
- Academic Affairs Office, Zhejiang Chinese Medical University, Hangzhou, China
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Mocanu V, Rajaruban S, Dang J, Kung JY, Deehan EC, Madsen KL. Repeated Fecal Microbial Transplantations and Antibiotic Pre-Treatment Are Linked to Improved Clinical Response and Remission in Inflammatory Bowel Disease: A Systematic Review and Pooled Proportion Meta-Analysis. J Clin Med 2021; 10:959. [PMID: 33804464 PMCID: PMC7957789 DOI: 10.3390/jcm10050959] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 02/17/2021] [Accepted: 02/19/2021] [Indexed: 12/13/2022] Open
Abstract
The response of patients with inflammatory bowel disease (IBD) to fecal microbial transplantation (FMT) has been inconsistent possibly due to variable engraftment of donor microbiota. This failure to engraft has resulted in the use of several different strategies to attempt optimization of the recipient microbiota following FMT. The purpose of our study was to evaluate the effects of two distinct microbial strategies-antibiotic pre-treatment and repeated FMT dosing-on IBD outcomes. A systematic literature review was designed and implemented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A medical librarian conducted comprehensive searches in MEDLINE, Embase, Scopus, Web of Science Core Collection, and Cochrane Library on 25 November 2019 and updated on 29 January 2021. Primary outcomes of interest included comparing relapse and remission rates in patients with IBD for a single FMT dose, repeated FMT dosages, and antibiotic pre-treatment groups. Twenty-eight articles (six randomized trials, 20 cohort trials, two case series) containing 976 patients were identified. Meta-analysis revealed that both repeated FMT and antibiotic pre-treatment strategies demonstrated improvements in pooled response and remission rates. These clinical improvements were associated with increases in fecal microbiota richness and α-diversity, as well as the enrichment of several short-chain fatty acid (SCFA)-producing anaerobes including Bifidobacterium, Roseburia, Lachnospiraceae, Prevotella, Ruminococcus, and Clostridium related species.
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Affiliation(s)
- Valentin Mocanu
- Department of Surgery, University of Alberta Hospital, University of Alberta, 8440 112 Street NW, Edmonton, AB T6G 2B7, Canada;
| | - Sabitha Rajaruban
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB T6G 2E1, Canada; (S.R.); (E.C.D.); (K.L.M.)
| | - Jerry Dang
- Department of Surgery, University of Alberta Hospital, University of Alberta, 8440 112 Street NW, Edmonton, AB T6G 2B7, Canada;
| | - Janice Y. Kung
- John W. Scott Health Sciences Library, University of Alberta, 2K3.28 Walter C. Mackenzie Health Sciences Centre, Edmonton, AB T6G 2R7, Canada;
| | - Edward C. Deehan
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB T6G 2E1, Canada; (S.R.); (E.C.D.); (K.L.M.)
| | - Karen L. Madsen
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB T6G 2E1, Canada; (S.R.); (E.C.D.); (K.L.M.)
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Żebrowska P, Łaczmańska I, Łaczmański Ł. Future Directions in Reducing Gastrointestinal Disorders in Children With ASD Using Fecal Microbiota Transplantation. Front Cell Infect Microbiol 2021; 11:630052. [PMID: 33718277 PMCID: PMC7952982 DOI: 10.3389/fcimb.2021.630052] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 01/22/2021] [Indexed: 12/16/2022] Open
Abstract
Research on the use of fecal microbiota transplantation (FMT) in the treatment of disorders related to digestive system ailments in children with autism spectrum disorders (ASDs) is a new attempt in a therapeutic approach. There are very little scientific evidences available on this emerging alternative method. However, it appears to be interesting not only because of its primary outcome, relieving the gastrointestinal (GI) symptoms, but also secondary therapeutic effect of alleviating autistic behavioral symptoms. FMT seems to be also promising method in the treatment of another group of pediatric patients, children with inflammatory bowel disease (IBD). The aim of this study is to discuss the potential use of FMT and modified protocols (MTT, microbiota transfer therapy) in the treatment of GI disorders in ASD children supported by reports on another disease, IBD concerning pediatric patients. Due to the few reports of the use of FMT in the treatment of children, these two patients groups were selected, although suffering from distant health conditions: neurodevelopmental disorder and gastrointestinal tract diseases, because of the the fact that they seem related in aspects of the presence of GI symptoms, disturbed intestinal microbiota, unexplained etiology of the condition and age range of patients. Although the outcomes for all are promising, this type of therapy is still an under-researched topic, studies in the group of pediatric patients are sparse, also there is a high risk of transmission of infectious and noninfectious elements during the procedure and no long-term effects on global health are known. For those reasons all obtained results should be taken with a great caution. However, in the context of future therapeutic directions for GI observed in neurodevelopmental disorders and neurodegenerative diseases, the topic seems worthy of attention.
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Affiliation(s)
- Paulina Żebrowska
- Laboratory of Genomics and Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | | | - Łukasz Łaczmański
- Laboratory of Genomics and Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
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Xu F, Li N, Wang C, Xing H, Chen D, Wei Y. Clinical efficacy of fecal microbiota transplantation for patients with small intestinal bacterial overgrowth: a randomized, placebo-controlled clinic study. BMC Gastroenterol 2021; 21:54. [PMID: 33549047 PMCID: PMC7866462 DOI: 10.1186/s12876-021-01630-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 01/26/2021] [Indexed: 12/16/2022] Open
Abstract
Background Small intestinal bacterial overgrowth (SIBO) is characterized by the condition that bacteria overgrowth in the small intestine. Fecal microbiota transplantation (FMT) has been applied as an effective tool for reestablishing the structure of gut microbiota. However, whether FMT could be applied as a routine SIBO treatment has not been investigated. Methods In this trial, 55 SIBO patients were enrolled. All participants were randomized in two groups, and were given FMT capsule or placebo capsules once a week for 4 consecutive weeks. Measurements including the lactulose hydrogen breath test gastrointestinal symptoms, as well as fecal microbiota diversity were assessed before and after FMT therapy. Results Gastrointestinal symptoms significantly improved in SIBO patients after treatment with FMT compared to participants in placebo group. The gut microbiota diversity of FMT group had a significant increase, while placebo group showed none. Conclusions This study suggests that applying FMT for patients with SIBO can alleviate gastrointestinal symptoms, indicating that FMT may be a promising and novel therapeutic regimen for SIBO. Trial registry This study was retrospectively registered with the Chinese Clinical Trial registry on 2019.7.10 (ID: ChiCTR1900024409, http://www.chictr.org.cn).
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Affiliation(s)
- Fenghua Xu
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China
| | - Ning Li
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China
| | - Chun Wang
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China
| | - Hanyang Xing
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China
| | - Dongfeng Chen
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China
| | - Yanling Wei
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China.
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Timmis K. Microbiome transplants to save the planetary surface biosphere. ENVIRONMENTAL MICROBIOLOGY REPORTS 2021; 13:50-53. [PMID: 33196144 DOI: 10.1111/1758-2229.12906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 11/11/2020] [Indexed: 06/11/2023]
Affiliation(s)
- Kenneth Timmis
- Institute for Microbiology, Technical University Braunschweig, Germany
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40
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Knežević D, Petković M. Faecal transplantation and Clostridioides difficile infection. SCRIPTA MEDICA 2021. [DOI: 10.5937/scriptamed52-32752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Faecal microbiota transplantation (FMT), known equally well as faecal transplantation or faecal bacteriotherapy, is the process of implanting the faecal suspension containing balanced microbiota from a healthy donor to the colon of a recipient patient. Excessive growth of Clostridioides difficile (C difficile) in the intestinal microbiota resulting from antibiotic consumption is currently a rising threat to public health. FMT is one of the most important, newer approaches to treating C difficile infections. Since C difficile is regarded as an opportunistic bacterium triggering disease in conditions of disturbed homeostasis of the intestinal microbiota, restoration of healthy intestinal microflora facilitates suppression of toxic strain of C difficile by anaerobic bacteria of normal intestinal microflora with concomitant cure. Nurses have important role in caring for patients after faecal transplantation.
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Qi X, Yang M, Stenberg J, Dey R, Fogwe L, Alam MS, Kimchi ET, Staveley-O'Carroll KF, Li G. Gut microbiota mediated molecular events and therapy in liver diseases. World J Gastroenterol 2020; 26:7603-7618. [PMID: 33505139 PMCID: PMC7789060 DOI: 10.3748/wjg.v26.i48.7603] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 11/24/2020] [Accepted: 12/06/2020] [Indexed: 02/06/2023] Open
Abstract
Gut microbiota is a community of microorganisms that reside in the gastrointestinal tract. An increasing number of studies has demonstrated that the gut-liver axis plays a critical role in liver homeostasis. Dysbiosis of gut microbiota can cause liver diseases, including nonalcoholic fatty liver disease and alcoholic liver disease. Preclinical and clinical investigations have substantiated that the metabolites and other molecules derived from gut microbiota and diet interaction function as mediators to cause liver fibrosis, cirrhosis, and final cancer. This effect has been demonstrated to be associated with dysregulation of intrahepatic immunity and liver metabolism. Targeting these findings have led to the development of novel preventive and therapeutic strategies. Here, we review the cellular and molecular mechanisms underlying gut microbiota-mediated impact on liver disease. We also summarize the advancement of gut microbiota-based therapeutic strategies in the control of liver diseases.
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Affiliation(s)
- Xiaoqiang Qi
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
- Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, United States
- VA Hospital, Harry S Truman Memorial VA Hospital, Columbia, MO 65201, United States
| | - Ming Yang
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
- Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, United States
- VA Hospital, Harry S Truman Memorial VA Hospital, Columbia, MO 65201, United States
| | - Joseph Stenberg
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
| | - Rahul Dey
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
| | - Leslie Fogwe
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
| | | | - Eric T Kimchi
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
- Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, United States
- VA Hospital, Harry S Truman Memorial VA Hospital, Columbia, MO 65201, United States
| | - Kevin F Staveley-O'Carroll
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
- Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, United States
- VA Hospital, Harry S Truman Memorial VA Hospital, Columbia, MO 65201, United States
| | - Guangfu Li
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
- Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, United States
- VA Hospital, Harry S Truman Memorial VA Hospital, Columbia, MO 65201, United States
- Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212, United States
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Niina A, Kibe R, Suzuki R, Yuchi Y, Teshima T, Matsumoto H, Kataoka Y, Koyama H. Fecal microbiota transplantation as a new treatment for canine inflammatory bowel disease. BIOSCIENCE OF MICROBIOTA FOOD AND HEALTH 2020; 40:98-104. [PMID: 33996366 PMCID: PMC8099633 DOI: 10.12938/bmfh.2020-049] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 11/10/2020] [Indexed: 12/14/2022]
Abstract
In human medicine, fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection. It has also been tested as a treatment for multiple gastrointestinal diseases, including inflammatory bowel disease (IBD). However, only a few studies have focused on the changes in the microbiome following FMT for canine IBD. Here, we performed FMT in nine dogs with IBD using the fecal matter of healthy dogs and investigated the subsequent changes in the fecal microbiome and clinical signs. In three dogs, the fecal microbiome was examined by 16S rRNA sequencing. Fusobacteria were observed at a low proportion in dogs with IBD. However, the post-FMT microbiome became diverse and showed a significant increase in Fusobacteria proportion. Fusobacterium was detected in the nine dogs by quantitative polymerase chain reaction. The proportion of Fusobacterium in the post-FMT fecal microbiome was significantly increased (p<0.05). The changes in clinical signs (e.g., vomiting, diarrhea, and weight loss) were evaluated according to the canine inflammatory bowel disease activity index. The score of this index significantly decreased in all dogs (p<0.05) with improvements in clinical signs. These improvements were related to the changes in the proportion of microbes, particularly the increase in Fusobacterium. The dogs with IBD showed a lower proportion of Fusobacterium than healthy dogs. This suggests that a low proportion of Fusobacterium is a characteristic feature of canine IBD and that Fusobacterium is involved in this disease. The results of this study may help elucidate the pathogenesis of this disease and its association with Fusobacterium.
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Affiliation(s)
- Ayaka Niina
- Laboratory of Veterinary Internal Medicine, School of Veterinary Medicine, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan
| | - Ryoko Kibe
- Laboratory of Veterinary Microbiology, School of Veterinary Medicine, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan
| | - Ryohei Suzuki
- Laboratory of Veterinary Internal Medicine, School of Veterinary Medicine, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan
| | - Yunosuke Yuchi
- Laboratory of Veterinary Internal Medicine, School of Veterinary Medicine, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan
| | - Takahiro Teshima
- Laboratory of Veterinary Internal Medicine, School of Veterinary Medicine, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan
| | - Hirotaka Matsumoto
- Laboratory of Veterinary Internal Medicine, School of Veterinary Medicine, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan
| | - Yasushi Kataoka
- Laboratory of Veterinary Microbiology, School of Veterinary Medicine, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan
| | - Hidekazu Koyama
- Laboratory of Veterinary Internal Medicine, School of Veterinary Medicine, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan
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Vural M, Gilbert B, Üstün I, Caglar S, Finckh A. Mini-Review: Human Microbiome and Rheumatic Diseases. Front Cell Infect Microbiol 2020; 10:491160. [PMID: 33304855 PMCID: PMC7693548 DOI: 10.3389/fcimb.2020.491160] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 10/14/2020] [Indexed: 12/16/2022] Open
Abstract
Rheumatoid arthritis and spondyloarthropathy are the most common inflammatory rheumatic diseases. As the human microbiome is involved in the immune homeostasis, it has the potential to be a key factor in the development of autoimmune diseases and rheumatic diseases. In this article, we review the role of various human microbiota on the pathogenesis of rheumatic diseases, focusing on spondylarthritis and rheumatoid arthritis.
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Affiliation(s)
- Meltem Vural
- Physical Medicine and Rehabilitation Clinic, University of Health Sciences, Bakırkoy Dr. Sadi Konuk Training Hospital, Istanbul, Turkey
| | - Benoit Gilbert
- Rheumatology Division, Department of Medicine, Geneva University Hospital (HUG), Geneva, Switzerland
| | - Işıl Üstün
- Physical Medicine and Rehabilitation Clinic, University of Health Sciences, Bakırkoy Dr. Sadi Konuk Training Hospital, Istanbul, Turkey
| | - Sibel Caglar
- Physical Medicine and Rehabilitation Clinic, University of Health Sciences, Bakırkoy Dr. Sadi Konuk Training Hospital, Istanbul, Turkey
| | - Axel Finckh
- Rheumatology Division, Department of Medicine, Geneva University Hospital (HUG), Geneva, Switzerland
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Steed DB, Wang T, Raheja D, Waldman AD, Babiker A, Dhere T, Kraft CS, Woodworth MH. Gram-Negative Taxa and Antimicrobial Susceptibility after Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection. mSphere 2020; 5:e00853-20. [PMID: 33055258 PMCID: PMC7565895 DOI: 10.1128/msphere.00853-20] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 09/20/2020] [Indexed: 12/15/2022] Open
Abstract
Fecal microbiota transplantation (FMT) has promising applications in reducing multidrug-resistant organism (MDRO) colonization and antibiotic resistance (AR) gene abundance. However, data on clinical microbiology results after FMT are limited. We examined the changes in antimicrobial susceptibility profiles in patients with Gram-negative infections in the year before and the year after treatment with FMT for recurrent Clostridioides difficile infection (RCDI). We also examined whether a history of FMT changed health care provider behavior with respect to culture ordering and antibiotic prescription. Medical records for RCDI patients who underwent FMT at Emory University between July 2012 and March 2017 were reviewed retrospectively. FMT-treated patients with Gram-negative culture data in the 1-year period preceding and the 1-year period following FMT were included. Demographic and clinical data were abstracted, including CDI history, frequency of Gram-negative cultures, microbiological results, and antibiotic prescription in response to positive cultures in the period following FMT. Twelve patients were included in this case series. We pooled data from infections at all body sites and found a decrease in the number of total and Gram-negative cultures post-FMT. We compared susceptibility profiles across taxa given the potential for horizontal transmission of AR elements and observed increased susceptibility to nitrofurantoin, trimethoprim-sulfamethoxazole, and the aminoglycosides. FMT did not drastically influence health care provider ordering of bacterial cultures or antibiotic prescribing practices. We observed a reduction in Gram-negative cultures and a trend toward increased antimicrobial susceptibility. This study supports further investigation of FMT as a means of improving antimicrobial susceptibility.IMPORTANCE Fecal microbiota transplantation (FMT), which is highly efficacious in treating recurrent C. difficile infection (RCDI), has a promising application in decolonization of multidrug-resistant organisms, reduction of antibiotic resistance gene abundance, and restoration of healthy intestinal microbiota. However, data representing clinical microbiology results after FMT are limited. We sought to characterize the differences in culture positivity and antimicrobial susceptibility profiles in patients with Gram-negative infections in the year before and the year after FMT for RCDI. Drawing on prior studies that had demonstrated the success of FMT in eradicating extraintestinal infections and the occurrence of patient-level interspecies transfer of resistance elements, we employed an agnostic analytic approach of reviewing the data irrespective of body site or species. In a small RCDI population, we observed an improvement in the antimicrobial susceptibility profile of Gram-negative bacteria following FMT, which supports further study of FMT as a strategy to combat antibiotic resistance.
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Affiliation(s)
| | - Tiffany Wang
- Emory University School of Medicine, Atlanta, Georgia, USA
| | | | - Alex D Waldman
- Emory University School of Medicine, Atlanta, Georgia, USA
| | - Ahmed Babiker
- Emory University School of Medicine, Department of Pathology and Laboratory Medicine, Atlanta, Georgia, USA
| | - Tanvi Dhere
- Emory University School of Medicine, Department of Medicine, Division of Digestive Diseases, Atlanta, Georgia, USA
| | - Colleen S Kraft
- Emory University School of Medicine, Department of Pathology and Laboratory Medicine, Atlanta, Georgia, USA
- Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, Georgia, USA
| | - Michael H Woodworth
- Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, Georgia, USA
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Garcia-Gutierrez E, Narbad A, Rodríguez JM. Autism Spectrum Disorder Associated With Gut Microbiota at Immune, Metabolomic, and Neuroactive Level. Front Neurosci 2020; 14:578666. [PMID: 33117122 PMCID: PMC7578228 DOI: 10.3389/fnins.2020.578666] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 09/16/2020] [Indexed: 12/21/2022] Open
Abstract
There is increasing evidence suggesting a link between the autism spectrum disorder (ASD) and the gastrointestinal (GI) microbiome. Experimental and clinical studies have shown that patients diagnosed with ASD display alterations of the gut microbiota. These alterations do not only extend to the gut microbiota composition but also to the metabolites they produce, as a result of its connections with diet and the bidirectional interaction with the host. Thus, production of metabolites and neurotransmitters stimulate the immune system and influence the central nervous system (CNS) by stimulation of the vagal nerve, as an example of the gut-brain axis pathway. In this review we compose an overview of the interconnectivity of the different GI-related elements that have been associated with the development and severity of the ASD in patients and animal models. We review potential biomarkers to be used in future studies to unlock further connections and interventions in the treatment of ASD.
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Affiliation(s)
- Enriqueta Garcia-Gutierrez
- Gut Microbes and Health Institute Strategic Program, Quadram Institute Bioscience, Norwich, United Kingdom
| | - Arjan Narbad
- Gut Microbes and Health Institute Strategic Program, Quadram Institute Bioscience, Norwich, United Kingdom
| | - Juan Miguel Rodríguez
- Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain
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Wang J, Yang HR, Wang DJ, Wang XX. Association between the gut microbiota and patient responses to cancer immune checkpoint inhibitors. Oncol Lett 2020; 20:342. [PMID: 33123253 PMCID: PMC7583737 DOI: 10.3892/ol.2020.12205] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 09/15/2020] [Indexed: 02/07/2023] Open
Abstract
Studies are increasingly investigating the association between the gut microbiota and the outcomes of immunotherapy in patients with cancer. Notably, certain studies have demonstrated that the gut microbiota serves a key role in regulating a patient's response to immunotherapy. In the present review, the potential associations between the gut microbiota, and cancer, host immunity and cancer immunotherapy are reviewed. Furthermore, the effects of fecal microbiota transplantation, antibiotics, probiotics, prebiotics, synbiotics, components of traditional Chinese medicine and various lifestyle factors on the gut microbiota and cancer immunotherapy outcomes are discussed. Certain dominant bacterial groups in the context of cancer immunotherapy and certain effective methods for optimizing immunotherapy by regulating the gut microbiota have been identified. Further investigation may enable the rapid conversion of these discoveries into practical products and clinically applicable methods.
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Affiliation(s)
- Jian Wang
- Department of Oncology, Luzhou People's Hospital, Luzhou, Sichuan 646000, P.R. China
| | - Hong-Ru Yang
- Department of Oncology, Luzhou People's Hospital, Luzhou, Sichuan 646000, P.R. China
| | - Dai-Jie Wang
- Department of Oncology, Luzhou People's Hospital, Luzhou, Sichuan 646000, P.R. China
| | - Xing-Xia Wang
- Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
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Terra DADA, Vilela EG, Silva ROS, LeÃo LA, Lima KS, Passos RIFÂ, Diniz AN, Coelho LGV. STRUCTURING A FECAL MICROBIOTA TRANSPLANTATION CENTER IN A UNIVERSITY HOSPITAL IN BRAZIL. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:434-458. [PMID: 33331486 DOI: 10.1590/s0004-2803.202000000-79] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 06/30/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) is an important therapeutic option for recurrent or refractory Clostridioides difficile infection, being a safe and effective method. Initial results suggest that FMT also plays an important role in other conditions whose pathogenesis involves alteration of the intestinal microbiota. However, its systematized use is not widespread, especially in Brazil. In the last decade, multiple reports and several cases emerged using different protocols for FMT, without standardization of methods and with variable response rates. In Brazil, few isolated cases of FMT have been reported without the implantation of a Fecal Microbiota Transplantation Center (FMTC). OBJECTIVE The main objective of this study is to describe the process of implanting a FMTC with a stool bank, in a Brazilian university hospital for treatment of recurrent and refractory C. difficile infection. METHODS The center was structured within the criteria required by international organizations such as the Food and Drug Administration, the European Fecal Microbiota Transplant Group and in line with national epidemiological and regulatory aspects. RESULTS A whole platform involved in structuring a transplant center with stool bank was established. The criteria for donor selection, processing and storage of samples, handling of recipients before and after the procedure, routes of administration, short and long-term follow-up of transplant patients were determined. Donor selection was conducted in three stages: pre-screening, clinical evaluation and laboratory screening. Most of the candidates were excluded in the first (75.4%) and second stage (72.7%). The main clinical exclusion criteria were: recent acute diarrhea, overweight (body mass index ≥25 kg/m2) and chronic gastrointestinal disorders. Four of the 134 candidates were selected after full screening, with a donor detection rate of 3%. CONCLUSION The implantation of a transplant center, unprecedented in our country, allows the access of patients with recurrent or refractory C. difficile infection to innovative, safe treatment, with a high success rate and little available in Brazil. Proper selection of qualified donors is vital in the process of implementing a FMTC. The rigorous clinical evaluation of donors allowed the rational use of resources. A transplant center enables treatment on demand, on a larger scale, less personalized, with more security and traceability. This protocol provides subsidies for conducting FMT in emerging countries.
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Affiliation(s)
| | - Eduardo Garcia Vilela
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas / EBSERH, Universidade Federal de Mina Gerais, Belo Horizonte, MG, Brasil
| | | | - Laiane Alves LeÃo
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas / EBSERH, Universidade Federal de Mina Gerais, Belo Horizonte, MG, Brasil
| | - Karine Sampaio Lima
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas / EBSERH, Universidade Federal de Mina Gerais, Belo Horizonte, MG, Brasil
| | | | - Amanda Nádia Diniz
- Universidade Federal de Minas Gerais, Escola de Veterinária, Belo Horizonte, MG, Brasil
| | - Luiz Gonzaga Vaz Coelho
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas / EBSERH, Universidade Federal de Mina Gerais, Belo Horizonte, MG, Brasil
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Takeuchi H, Higuchi K, Yoshikane Y, Takagi R, Tokuhiro S, Takenaka K, Oboshi W, Kimura A, Islam JM, Kaneko A, Sato S, Ishizuka S. Drinking Refined Deep-Sea Water Improves the Gut Ecosystem with Beneficial Effects on Intestinal Health in Humans: A Randomized Double-Blind Controlled Trial. Nutrients 2020; 12:nu12092646. [PMID: 32878045 PMCID: PMC7551512 DOI: 10.3390/nu12092646] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 08/27/2020] [Accepted: 08/27/2020] [Indexed: 12/13/2022] Open
Abstract
World health trends are focusing on a balanced food and beverage intake for healthy life. Refined deep-sea water (RDSW), obtained from deep-sea water collected offshore in Muroto (Japan), is mineral-rich drinking water. We previously reported that drinking RDSW improves human gut health. Here, we analyzed the effect of drinking RDSW on the gut ecosystem to understand this effect. This was a randomized double-blind controlled trial. Ninety-eight healthy adults were divided into two groups: RDSW or mineral water (control). The participants consumed 1 L of either water type daily for 12 weeks. A self-administered questionnaire and stool and urine samples were collected through the intervention. The following were determined: fecal biomarkers of secretory immunoglobulin A (sIgA), five putrefactive products, and nine short-chain-fatty-acids (SCFAs) as the primary outcomes; and three urinary isoflavones and the questionnaire as secondary outcomes. In post-intervention in the RDSW group, we found increased concentrations of five SCFAs and decreased concentrations of phenol and sIgA (p < 0.05). The multiple logistic analysis demonstrated that RDSW significantly affected two biomarkers (acetic and 3-methylbutanoic acids) of the five SCFAs mentioned above (p < 0.05). Similarly, the concentrations of urinary isoflavones tended to increase in post-intervention in the RDSW group. Constipation was significantly alleviated in the RDSW group (94%) compared with the control group (60%). Drinking RDSW improves the intestinal environment, increasing fecal SCFAs and urinary isoflavones, which leads to broad beneficial effects in human.
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Affiliation(s)
- Hiroaki Takeuchi
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, 4-3 Kouzunomori, Narita-City 286-8686, Chiba, Japan; (W.O.); (A.K.); (J.M.I.); (A.K.); (S.S.)
- Department of Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku-City 783-8505, Kochi, Japan; (R.T.); (S.T.)
- Correspondence: ; Tel.: +81-476-20-7762
| | - Keiro Higuchi
- Center for Regional Collaboration, Kochi University, 2-17-47 Asakurahonmachi, Kochi-City 780-8073, Kochi, Japan; (K.H.); (S.I.)
| | - Yu Yoshikane
- Department of Human Living Sciences, Notre Dame Seishin University, 2-16-9 Ifuku-cho, Kita-ku, Okayama-City 700-8516, Okayama, Japan;
| | - Ryo Takagi
- Department of Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku-City 783-8505, Kochi, Japan; (R.T.); (S.T.)
| | - Shinji Tokuhiro
- Department of Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku-City 783-8505, Kochi, Japan; (R.T.); (S.T.)
| | - Koichi Takenaka
- DyDo-T Beverage Co. Ltd., 1310-1 Hanechou-ko, Muroto-City 781-6741, Kochi, Japan;
| | - Wataru Oboshi
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, 4-3 Kouzunomori, Narita-City 286-8686, Chiba, Japan; (W.O.); (A.K.); (J.M.I.); (A.K.); (S.S.)
| | - Asako Kimura
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, 4-3 Kouzunomori, Narita-City 286-8686, Chiba, Japan; (W.O.); (A.K.); (J.M.I.); (A.K.); (S.S.)
| | - Jahirul Md. Islam
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, 4-3 Kouzunomori, Narita-City 286-8686, Chiba, Japan; (W.O.); (A.K.); (J.M.I.); (A.K.); (S.S.)
| | - Ayami Kaneko
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, 4-3 Kouzunomori, Narita-City 286-8686, Chiba, Japan; (W.O.); (A.K.); (J.M.I.); (A.K.); (S.S.)
| | - Shouichi Sato
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, 4-3 Kouzunomori, Narita-City 286-8686, Chiba, Japan; (W.O.); (A.K.); (J.M.I.); (A.K.); (S.S.)
| | - Satoshi Ishizuka
- Center for Regional Collaboration, Kochi University, 2-17-47 Asakurahonmachi, Kochi-City 780-8073, Kochi, Japan; (K.H.); (S.I.)
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The Effectiveness of Multi-Session FMT Treatment in Active Ulcerative Colitis Patients: A Pilot Study. Biomedicines 2020; 8:biomedicines8080268. [PMID: 32756350 PMCID: PMC7459721 DOI: 10.3390/biomedicines8080268] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 07/27/2020] [Accepted: 07/29/2020] [Indexed: 12/12/2022] Open
Abstract
The modification of the microbiome through fecal microbiota transplantation (FMT) is becoming a very promising therapeutic option for inflammatory bowel disease (IBD) patients. Our pilot study aimed to assess the effectiveness of multi-session FMT treatment in active ulcerative colitis (UC) patients. Ten patients with UC were treated with multi-session FMT (200 mL) from healthy donors, via colonoscopy/gastroscopy. Patients were evaluated as follows: at baseline, at week 7, and after 6 months, routine blood tests (including C reactive protein (CRP) and calprotectin) were performed. 16S rRNA gene (V3V4) sequencing was used for metagenomic analysis. The severity of UC was classified based on the Truelove–Witts index. The assessment of microbial diversity showed significant differences between recipients and healthy donors. FMT contributed to long-term, significant clinical and biochemical improvement. Metagenomic analysis revealed an increase in the amount of Lactobacillaceaea, Micrococcaceae, Prevotellaceae, and TM7 phylumsp.oral clone EW055 during FMT, whereas Staphylococcaceae and Bacillaceae declined significantly. A positive increase in the proportion of the genera Bifidobacterium, Lactobacillus, Rothia, Streptococcus, and Veillonella and a decrease in Bacillus, Bacteroides, and Staphylococcus were observed based on the correlation between calprotectin and Bacillus and Staphylococcus; ferritin and Lactobacillus, Veillonella, and Bifidobacterium abundance was indicated. A positive change in the abundance of Firmicutes was observed during FMT and after 6 months. The application of multi-session FMT led to the restoration of recipients’ microbiota and resulted in the remission of patients with active UC.
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Okahara K, Ishikawa D, Nomura K, Ito S, Haga K, Takahashi M, Shibuya T, Osada T, Nagahara A. Matching between Donors and Ulcerative Colitis Patients Is Important for Long-Term Maintenance after Fecal Microbiota Transplantation. J Clin Med 2020; 9:jcm9061650. [PMID: 32486476 PMCID: PMC7355579 DOI: 10.3390/jcm9061650] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 05/27/2020] [Accepted: 05/28/2020] [Indexed: 12/11/2022] Open
Abstract
We previously demonstrated that fresh fecal microbiota transplantation (FMT) following triple antibiotic therapy (amoxicillin, fosfomycin, metronidazole (AFM); A-FMT) resulted in effective colonization of Bacteroidetes species, leading to short-term clinical response in ulcerative colitis (UC). Its long-term efficacy and criteria for donor selection are unknown. Here, we analyzed the long-term efficacy of A-FMT compared to AFM monotherapy (mono-AFM). AFM was administered to patients with mild to severe UC for 2 weeks until 2 days before fresh FMT. Clinical response and efficacy maintenance were defined by the decrease and no exacerbation in clinical activity index. The population for intention-to-treat analysis comprised 92 patients (A-FMT, n = 55; mono-AFM, n = 37). Clinical response was observed at 4 weeks post-treatment (A-FMT, 56.3%; mono-AFM, 48.6%). Maintenance rate of responders at 24 months post-treatment was significantly higher with A-FMT than mono-AFM (p = 0.034). Significant differences in maintenance rate according to the age difference between donors and patients were observed. Additionally, sibling FMT had a significantly higher maintenance rate than parent–child FMT. Microbial analysis of patients who achieved long-term maintenance showed that some exhibited similarity to their donors, particularly Bacteroidetes species. Thus, A-FMT exhibited long-term efficacy. Therefore, matching between donors and UC patients may be helpful in effectively planning the FMT regimen.
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Affiliation(s)
| | - Dai Ishikawa
- Correspondence: ; Tel.: +81-(0)3-5802-1060; Fax: +81-(0)3-3813-8862
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