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Zhang Y, Mo C, Ai P, He X, Xiao Q, Yang X. Pharmacomicrobiomics: a new field contributing to optimizing drug therapy in Parkinson's disease. Gut Microbes 2025; 17:2454937. [PMID: 39875349 PMCID: PMC11776486 DOI: 10.1080/19490976.2025.2454937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 11/19/2024] [Accepted: 01/13/2025] [Indexed: 01/30/2025] Open
Abstract
Gut microbiota, which act as a determinant of pharmacokinetics, have long been overlooked. In recent years, a growing body of evidence indicates that the gut microbiota influence drug metabolism and efficacy. Conversely, drugs also exert a substantial influence on the function and composition of the gut microbiota. Pharmacomicrobiomics, an emerging field focusing on the interplay of drugs and gut microbiota, provides a potential foundation for making certain advances in personalized medicine. Understanding the communication between gut microbiota and antiparkinsonian drugs is critical for precise treatment of Parkinson's disease. Here, we provide a historical overview of the interplay between gut microbiota and antiparkinsonian drugs. Moreover, we discuss potential mechanistic insights into the complex associations between gut microbiota and drug metabolism. In addition, we also draw attention to microbiota-based biomarkers for predicting antiparkinsonian drug efficacy and examine current state-of-the-art knowledge of microbiota-based strategies to optimize drug therapy in Parkinson's disease.
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Affiliation(s)
- Yi Zhang
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chengjun Mo
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Penghui Ai
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoqin He
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qin Xiao
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaodong Yang
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Li Y, Zhang XH, Wang ZK. Microbiota treatment of functional constipation: Current status and future prospects. World J Hepatol 2024; 16:776-783. [PMID: 38818289 PMCID: PMC11135260 DOI: 10.4254/wjh.v16.i5.776] [Citation(s) in RCA: 1] [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: 12/27/2023] [Revised: 02/05/2024] [Accepted: 04/03/2024] [Indexed: 05/22/2024] Open
Abstract
Functional constipation (FC) is a common disorder that is characterized by difficult stool passage, infrequent bowel movement, or both. FC is highly prevalent, recurs often, accompanies severe diseases, and affects quality of life; therefore, safe and effective therapy with long-term benefits is urgently needed. Microbiota treatment has potential value for FC treatment. Microbiota treatments include modulators such as probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT). Some probiotics and prebiotics have been adopted, and the efficacy of other microbiota modulators is being explored. FMT is considered an emerging field because of its curative effects; nevertheless, substantial work must be performed before clinical implementation.
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Affiliation(s)
- Yan Li
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Xiao-Han Zhang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- Medical School, Nankai University, Tianjin 300071, China
| | - Zi-Kai Wang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China.
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Nita AF, Chanpong A, Nikaki K, Rybak A, Thapar N, Borrelli O. Recent advances in the treatment of gastrointestinal motility disorders in children. Expert Rev Gastroenterol Hepatol 2023; 17:1285-1300. [PMID: 38096022 DOI: 10.1080/17474124.2023.2295495] [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: 04/12/2023] [Accepted: 12/12/2023] [Indexed: 01/12/2024]
Abstract
INTRODUCTION Pediatric gastrointestinal motility disorders represent some of the most challenging clinical conditions with largely undefined pathogenetic pathways and therefore limited therapeutic options. Herein, we provide an overview of the recent advances in treatment options for these disorders and their clinical impact. AREAS COVERED PubMed and Medline databases were searched for relevant articles related to the treatment of achalasia, esophageal atresia, gastroparesis, PIPO and constipation published between 2017 and 2022. In this article, we review and summarize recent advances in management of gastrointestinal motility disorders in children with a particular focus on emerging therapies as well as novel diagnostic modalities that help guide their application or develop new, more targeted treatments. EXPERT OPINION Gastrointestinal motility disorders represent one of the most challenging conundrums in pediatric age and despite significant advances in investigative tools, the palette of treatment options remain limited. Overall, while pharmacological options have failed to bring a curative solution, recent advances in minimal invasive therapeutic and diagnostic techniques have emerged as potential keys to symptom and quality of life improvement, such as ENDOFLIP, POEM, cine-MRI, fecal microbiota transplantation.
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Affiliation(s)
- Andreia Florina Nita
- Department of Pediatric Gastroenterology, Great Ormond Street Hospital, London, UK
| | - Atchariya Chanpong
- Department of Pediatric Gastroenterology, Great Ormond Street Hospital, London, UK
- Division of Gastroenterology and Hepatology, Department of Paediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
- Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, Brisbane, Australia
- Stem Cells and Regenerative Medicine, UCL Institute of Child Health, London, UK
| | - Kornilia Nikaki
- Department of Pediatric Gastroenterology, Great Ormond Street Hospital, London, UK
| | - Anna Rybak
- Department of Pediatric Gastroenterology, Great Ormond Street Hospital, London, UK
| | - Nikhil Thapar
- Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, Brisbane, Australia
- Stem Cells and Regenerative Medicine, UCL Institute of Child Health, London, UK
- School of Medicine, University of Queensland, Brisbane, Australia
- Woolworths Centre for Child Nutrition Research, Queensland University of Technology, Brisbane, Australia
| | - Osvaldo Borrelli
- Department of Pediatric Gastroenterology, Great Ormond Street Hospital, London, UK
- Stem Cells and Regenerative Medicine, UCL Institute of Child Health, London, UK
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Gut microbiota: a new avenue to reveal pathological mechanisms of constipation. Appl Microbiol Biotechnol 2022; 106:6899-6913. [PMID: 36190540 DOI: 10.1007/s00253-022-12197-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 09/19/2022] [Accepted: 09/21/2022] [Indexed: 11/27/2022]
Abstract
Constipation is very pervasive all over the world. It is a common multifactorial gastrointestinal disease, and its etiology and pathomechanism are not completely clear. Now, increasing evidence shows that intestinal flora is closely related to constipation. Intestinal flora is the largest microbiota in the human body and has powerful metabolic functions. Intestinal flora can produce a variety of metabolites, such as bile acids, short-chain fatty acids, tryptophan metabolites, and methane, which have important effects on intestinal motility and secretion. The host can also monitor the intestinal flora and regulate gut dysbacteriosis in constipation. To explore the relationship between intestinal flora and host, the combination of multiomics technology has become the powerful and effective method. Furthermore, the homeostasis restoration of intestinal flora also provides a new strategy for the treatment of constipation. This review aims to explore the interaction between intestinal flora and host in constipation, which contributes to disclose the pathogenesis of constipation and the development of novel drugs for the treatment of constipation from the perspective of intestinal flora. KEY POINTS: • This review highlights the regulation of gut microbiota on the intestinal motility and secretion of host. • The current review gives an insight into the role of the host on the recognition and regulation of intestinal ecology under constipation. • The article also introduces some novel methods of current gut microbiota research and gut microbiota-based constipation therapies.
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Pan R, Wang L, Xu X, Chen Y, Wang H, Wang G, Zhao J, Chen W. Crosstalk between the Gut Microbiome and Colonic Motility in Chronic Constipation: Potential Mechanisms and Microbiota Modulation. Nutrients 2022; 14:nu14183704. [PMID: 36145079 PMCID: PMC9505360 DOI: 10.3390/nu14183704] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 09/05/2022] [Accepted: 09/06/2022] [Indexed: 11/16/2022] Open
Abstract
Chronic constipation (CC) is a highly prevalent and burdensome gastrointestinal disorder. Accumulating evidence highlights the link between imbalances in the gut microbiome and constipation. However, the mechanisms by which the microbiome and microbial metabolites affect gut movement remain poorly understood. In this review, we discuss recent studies on the alteration in the gut microbiota in patients with CC and the effectiveness of probiotics in treating gut motility disorder. We highlight the mechanisms that explain how the gut microbiome and its metabolism are linked to gut movement and how intestinal microecological interventions may counteract these changes based on the enteric nervous system, the central nervous system, the immune function, and the ability to modify intestinal secretion and the hormonal milieu. In particular, microbiota-based approaches that modulate the levels of short-chain fatty acids and tryptophan catabolites or that target the 5-hydroxytryptamine and Toll-like receptor pathways may hold therapeutic promise. Finally, we discuss the existing limitations of microecological management in treating constipation and suggest feasible directions for future research.
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Affiliation(s)
- Ruili Pan
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Linlin Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Xiaopeng Xu
- The Department of Clinical Laboratory, Wuxi Xishan People’s Hospital, Wuxi 214105, China
| | - Ying Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Haojue Wang
- The Department of of Obstetrics and Gynecology, Wuxi Xishan People’s Hospital, Wuxi 214105, China
- Correspondence: (H.W.); (J.Z.); Tel.: +86-510-8240-2084 (H.W.); +86-510-8591-2155 (J.Z.)
| | - Gang Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
- Correspondence: (H.W.); (J.Z.); Tel.: +86-510-8240-2084 (H.W.); +86-510-8591-2155 (J.Z.)
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
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Liu QH, Ke X, Xiao C. Current Applications of Fecal Microbiota Transplantation in Functional Constipation. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:7931730. [PMID: 35873640 PMCID: PMC9300281 DOI: 10.1155/2022/7931730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 06/22/2022] [Indexed: 11/30/2022]
Abstract
Functional constipation (FC) is a common condition that would be hard to treat in clinical practice with a prevalence incidence in the population. Pharmacotherapy is a common treatment modality. However, clinical effects are limited and patients continue to suffer from it. In recent years, with the gradual increase in research on gut microbiota, it is understood that dysbiosis of the gut microbiota is importantly associated with the development of constipation. Recent studies have shown that fecal microbiota transplantation (FMT) is an effective method for restoring gut microbiota, as well as being efficacious in the treatment of FC. This mini review explains the characteristics of gut microbiota in FC patients, the mechanism of action of FMT, treatment modalities, current efficacy, and related problems. The purpose is to provide research directions and references for the future applications of FMT in FC.
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Affiliation(s)
- Qi-Hong Liu
- The Second People's Hospital Affiliated to Fujian University of Chinese Medicine, Fuzhou 350003, China
- Fujian Clinical Medical Research Centre of Chinese Medicine for Spleen and Stomach, Fuzhou 350003, China
| | - Xiao Ke
- The Second People's Hospital Affiliated to Fujian University of Chinese Medicine, Fuzhou 350003, China
- Fujian Clinical Medical Research Centre of Chinese Medicine for Spleen and Stomach, Fuzhou 350003, China
| | - Cenxin Xiao
- The Second People's Hospital Affiliated to Fujian University of Chinese Medicine, Fuzhou 350003, China
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