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Ranhotra HS. Discrete interplay of gut microbiota L-tryptophan metabolites in host biology and disease. Mol Cell Biochem 2024; 479:2273-2290. [PMID: 37861881 DOI: 10.1007/s11010-023-04867-0] [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: 06/14/2023] [Accepted: 09/24/2023] [Indexed: 10/21/2023]
Abstract
The gut microbiota and the host maintain a conjoint relationship and together achieve optimal physiology via a multitude of interactive signalling cues. Dietary-derived L-tryptophan (L-trp) is enzymatically metabolized by the resident symbiotic gut microbiota to indole and various indole derivatives. Indole and indole metabolites secreted by the gut bacteria act locally in the intestinal cells as well as distally and modulate tissue-specific functions which are beneficial to the host. Functions attributed to these microbial indole metabolites in the host include regulation of intestinal permeability, immunity and mucosal roles, inflammation, and insulin sensitivity. On the other hand, dysregulation of gut microbiota L-trp metabolism compromises the optimal availability of indole and indole metabolites and can induce the onset of metabolic disorders, inflammation, liver steatosis, and decrease gut barrier integrity. Gut dysbiosis is regarded as one of the prime reasons for this deregulated microbial-derived indole metabolites. A number of indole metabolites from the gut bacteria have been identified recently displaying variable affinity towards xenobiotic nuclear receptors. Microbial metabolite mimicry concept can be used to design and develop novel indole-moiety-containing compounds with higher affinity towards the receptors and efficacy in preclinical studies. Such compounds may serve as therapeutic drugs in clinical trials in the future. In this article, I review L-trp metabolism in the host and gut microbiota and the various physiological functions, patho-physiologies associated with the microbial-released indole metabolites in the host, including the metabolite mimicry-based concept to develop tailored indole-containing novel experimental drugs.
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Affiliation(s)
- Harmit S Ranhotra
- Department of Biochemistry, St. Edmund's College, Shillong, 793 003, India.
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Zhang H, Xia Y, Wang G, Xiong Z, Wei G, Liao Z, Qian Y, Cai Z, Ai L. Lactobacillus plantarum AR495 improves colonic transport hyperactivity in irritable bowel syndrome through tryptophan metabolism. Food Funct 2024; 15:7416-7429. [PMID: 38899520 DOI: 10.1039/d4fo01087f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/21/2024]
Abstract
Lactobacillus plantarum AR495 is a widely used probiotic for the treatment of various digestive diseases, including irritable bowel syndrome (IBS). However, the specific mechanisms of L. plantarum AR495 in alleviating IBS remain unclear. Abnormal intestinal tryptophan metabolism can cause disordered immune responses, gastrointestinal peristalsis, digestion and sensation, which is closely related to IBS pathogenesis. The aim of this study is to explore the effects and mechanisms of L. plantarum AR495 in regulating tryptophan metabolism. Primarily, tryptophan and its related metabolites in patients with IBS and healthy people were analyzed, and an IBS rat model of acetic acid enema plus restraint stress was established to explore the alleviation pathway of L. plantarum AR495 in tryptophan metabolism. It was found that the 5-HT pathway was significantly changed, and the 5-HTP and 5-HT metabolites were significantly increased in the feces of patients with IBS, which were consistent with the results obtained for the IBS rat model. Maladjusted 5-HT could increase intestinal peristalsis and lead to an increase in the fecal water content and shapeless stool in rats. On the contrary, these two metabolites could be restored to normal levels via intragastric administration of L. plantarum AR495. Further study of the metabolic pathway showed that L. plantarum AR495 could effectively reduce the abundance of 5-HT by inhibiting the expression of enterochromaffin cells rather than promoting its decomposition. In addition, the results showed that L. plantarum AR495 did not affect the expression of SERT. To sum up, L. plantarum AR495 could restore the normal levels of 5-HT by inhibiting the abnormal proliferation of enterochromaffin cells and the excessive activation of TPH1 to inhibit the intestinal peristalsis in IBS. These findings provide insights for the use of probiotics in the treatment of IBS and other diarrheal diseases.
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Affiliation(s)
- Hongyun Zhang
- Shanghai Engineering Research Center of Food Microbiology, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
- Business school, University of Shanghai for Science and Technology, Shanghai, 200093, China
| | - Yongjun Xia
- Shanghai Engineering Research Center of Food Microbiology, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
| | - Guangqiang Wang
- Shanghai Engineering Research Center of Food Microbiology, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
| | - Zhiqiang Xiong
- Shanghai Engineering Research Center of Food Microbiology, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
| | - Guoliang Wei
- Business school, University of Shanghai for Science and Technology, Shanghai, 200093, China
| | - Zhuan Liao
- Department of Gastroenterol, Digestive Endoscopy Center, Changhai Hospital, Shanghai, 200433, China
| | - Yangyan Qian
- Department of Gastroenterol, Digestive Endoscopy Center, Changhai Hospital, Shanghai, 200433, China
| | - Zongwei Cai
- State Key Laboratory of Environmental & Biological Analysis, Hong Kong Baptist University, Hong Kong Special Administrative region of China, China
| | - Lianzhong Ai
- Shanghai Engineering Research Center of Food Microbiology, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
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Napolitano M, Fasulo E, Ungaro F, Massimino L, Sinagra E, Danese S, Mandarino FV. Gut Dysbiosis in Irritable Bowel Syndrome: A Narrative Review on Correlation with Disease Subtypes and Novel Therapeutic Implications. Microorganisms 2023; 11:2369. [PMID: 37894027 PMCID: PMC10609453 DOI: 10.3390/microorganisms11102369] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 09/19/2023] [Accepted: 09/20/2023] [Indexed: 10/29/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. It can be subclassified in different subtypes according to the main clinical manifestation: constipation, diarrhea, mixed, and unclassified. Over the past decade, the role of gut microbiota in IBS has garnered significant attention in the scientific community. Emerging research spotlights the intricate involvement of microbiota dysbiosis in IBS pathogenesis. Studies have demonstrated reduced microbial diversity and stability and specific microbial alterations for each disease subgroup. Microbiota-targeted treatments, such as antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and even diet, offer exciting prospects for managing IBS. However, definitive conclusions are hindered by the heterogeneity of these studies. Further research should focus on elucidating the mechanisms, developing microbiome-based diagnostics, and enabling personalized therapies tailored to an individual's microbiome profile. This review takes a deep dive into the microscopic world inhabiting our guts, and its implications for IBS. Our aim is to elucidate the complex interplay between gut microbiota and each IBS subtype, exploring novel microbiota-targeted treatments and providing a comprehensive overview of the current state of knowledge.
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Affiliation(s)
- Maria Napolitano
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
| | - Ernesto Fasulo
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
| | - Federica Ungaro
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
- Division of Immunology, Transplantation and Infectious Disease, IRCCS Ospedale San Raffaele, 20132 Milan, Italy
| | - Luca Massimino
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
- Division of Immunology, Transplantation and Infectious Disease, IRCCS Ospedale San Raffaele, 20132 Milan, Italy
| | - Emanuele Sinagra
- Gastroenterology & Endoscopy Unit, Fondazione Istituto G. Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy;
| | - Silvio Danese
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
- Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Francesco Vito Mandarino
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
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Halkjær SI, Lo B, Cold F, Højer Christensen A, Holster S, König J, Brummer RJ, Aroniadis OC, Lahtinen P, Holvoet T, Gluud LL, Petersen AM. Fecal microbiota transplantation for the treatment of irritable bowel syndrome: A systematic review and meta-analysis. World J Gastroenterol 2023; 29:3185-3202. [PMID: 37346153 PMCID: PMC10280798 DOI: 10.3748/wjg.v29.i20.3185] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/06/2023] [Accepted: 04/18/2023] [Indexed: 05/26/2023] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal disorder in developed countries and reduces patients’ quality of life, hinders their ability to work, and increases health care costs. A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS, also known as ‘gut dysbiosis’. Fecal microbiota transplantation (FMT) has been suggested as a treatment for IBS.
AIM To assess the efficacy and safety of FMT for the treatment of IBS.
METHODS We searched Cochrane Central, MEDLINE, EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials (RCTs) investigating the effectiveness of FMT compared to placebo (including autologous FMT) in treating IBS. The primary outcome was the number of patients with improvements of symptoms measured using a validated, global IBS symptoms score. Secondary outcomes were changes in quality-of-life scores, non-serious and serious adverse events. Risk ratios (RR) and corresponding 95%CI were calculated for dichotomous outcomes, as were the mean differences (MD) and 95%CI for continuous outcomes. The Cochrane risk of bias tool was used to assess the quality of the trials. GRADE criteria were used to assess the overall quality of the evidence.
RESULTS Eight RCTs (484 participants) were included in the review. FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo (RR 1.19, 95%CI: 0.68-2.10). Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group (RR 1.17, 95%CI: 0.63-2.15). One serious adverse event occurred in the FMT group and two in the placebo group (RR 0.42, 95%CI: 0.07-2.60). Endoscopic FMT delivery resulted in a significant improvement in symptoms, while capsules did not. FMT did not improve the quality of life of IBS patients but, instead, appeared to reduce it, albeit non significantly (MD -6.30, 95%CI: -13.39-0.79). The overall quality of the evidence was low due to moderate-high inconsistency, the small number of patients in the studies, and imprecision.
CONCLUSION We found insufficient evidence to support or refute the use of FMT for IBS. Larger trials are needed.
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Affiliation(s)
- Sofie Ingdam Halkjær
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Copenhagen IBD Center, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
| | - Bobby Lo
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Copenhagen IBD Center, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
| | - Frederik Cold
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Copenhagen IBD Center, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
| | | | - Savanne Holster
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro 70362, Sweden
| | - Julia König
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro 70362, Sweden
| | - Robert Jan Brummer
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro 70362, Sweden
| | - Olga C Aroniadis
- Department of Internal Medicine, Division of Gastroenterology, Renaissance School of Medicine, Stony Brook University Hospital, New York, NY 11794-8434, United States
| | - Perttu Lahtinen
- Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti 15850, Finland
- Department of Medicine, University of Helsinki, Helsinki 00014, Finland
| | - Tom Holvoet
- Department of Gastroenterology, University Hospital Ghent, Ghent 9000, Belgium
| | - Lise Lotte Gluud
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen 2200, Denmark
| | - Andreas Munk Petersen
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Copenhagen IBD Center, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen 2200, Denmark
- Department of Clinical Microbiology, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
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Ren Y, Hou S, Sui Y, Chang N, Zhou Y, Sun C. Sonchus arvensis L. water extract attenuates dextran sulfate sodium-induced colitis by adjusting gut microbiota. Heliyon 2023; 9:e14168. [PMID: 36923824 PMCID: PMC10009677 DOI: 10.1016/j.heliyon.2023.e14168] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 02/18/2023] [Accepted: 02/23/2023] [Indexed: 03/06/2023] Open
Abstract
Sonchus arvensisL. (SA) is a traditional Chinese food and medicine termed "Ju Mai Cai". The aim of this study was to investigate the protective effects of an aqueous extract of SA on dextran sulfate sodium (DSS) - induced colitis in mice by adjusting the diversity of gut microbiota. Male C57BL/6 mice were randomly divided into four groups: CL (control group); ML group (DSS only); SA group (SA extract); and MS group (SA extract + DSS). The protective effect of SA on ulcerative disease was estimated by several analyses (i.e., body weight loss, diarrhea, bloody stools, disease activity index scores, and hematoxylin and eosin staining). The effect of SA on gut microbiota was determined by analysis of the 16S ribosomal RNA gene sequences. The results indicated that MS significantly attenuated the body weight loss. The disease activity index scores were markedly lower in the MS group versus in the ML group. Moreover, the length of the colon was significantly improved in the MS groups versus in the ML group. Pathological changes were markedly improved following the administration of SA to mice with DSS-induced ulcerative disease. The results of Beta diversity analysis revealed that the composition of gut microbiota was significantly different between groups. Taken together, the results indicated that SA extract may prevent ulcerative colitis.
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Affiliation(s)
- Yachao Ren
- School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin, 300000, China.,Harbin Medical University-Daqing, Daqing 163319, China
| | - Shenghua Hou
- Harbin Medical University-Daqing, Daqing 163319, China
| | - Yilei Sui
- Harbin Medical University-Daqing, Daqing 163319, China
| | - Naidan Chang
- Harbin Medical University-Daqing, Daqing 163319, China
| | - Yulong Zhou
- College of Animal Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, China
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Dai YX, Tai YH, Chang YT, Chen TJ, Chen MH. Bidirectional association between alopecia areata and irritable bowel syndrome: A nationwide population-based cohort study. Australas J Dermatol 2022; 63:e127-e132. [PMID: 35196396 DOI: 10.1111/ajd.13809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/07/2022] [Accepted: 02/06/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND Alopecia areata (AA) and irritable bowel syndrome (IBS) are two distinct diseases that share a similar pathophysiology; however, the relationship between these two diseases is unknown. This study aimed to investigate the bidirectional relationship between AA and IBS. METHODS Participants were recruited from the National Health Insurance Research Database in Taiwan. We included 5446 patients with AA and 21 784 matched controls to assess the risk of IBS, and 56 429 patients with IBS and 225 716 matched controls to assess the risk of AA. The Cox proportional-hazards regression model was used to calculate the adjusted hazard ratio (aHR). RESULTS After adjustment for potential confounders, patients with AA had an aHR of 5.20 [95% confidence interval (CI) 3.97-6.82] for IBS in comparison with the controls. Furthermore, compared with the controls, IBS patients had an aHR of 5.38 (95% CI 3.95-7.34) for AA. CONCLUSION AA is bidirectionally associated with IBS. Further investigation is needed to elucidate the shared pathogenesis underlying these two diseases.
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Affiliation(s)
- Ying-Xiu Dai
- Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ying-Hsuan Tai
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.,Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yun-Ting Chang
- Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Tzeng-Ji Chen
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Mu-Hong Chen
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
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Zhang X, Liu L, Bai W, Han Y, Hou X. Evolution of Intestinal Microbiota of Asphyxiated Neonates Within 1 Week and Its Relationship With Neural Development at 6 Months. Front Pediatr 2021; 9:690339. [PMID: 34497782 PMCID: PMC8419515 DOI: 10.3389/fped.2021.690339] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 07/22/2021] [Indexed: 12/27/2022] Open
Abstract
Introduction: Asphyxia is an emergent condition in neonates that may influence the function of the nervous system. Research has shown that intestinal microbiota is very important for neurodevelopment. Studies regarding the association between gut microbiota and neurodevelopment outcome in asphyxiated newborns remain scarce. Objective: To study the microbial characteristics of asphyxiated neonates within 1 week of life and to investigate their relationship with neural development at 6 months. Methods: The feces produced on days 1, 3, and 5, and the clinical data of full-term neonates with asphyxia and without asphyxia, delivered from March 2019 to October 2020 at Peking University First Hospital, were collected. We used 16S ribosomal deoxyribonucleic acid amplicon sequencing to detect the intestinal microbiota of asphyxiated neonates and neonates in the control group. We followed up asphyxiated neonates for 6 months and used the Ages and Stages Questionnaires-3 (ASQ-3) to evaluate their development. Results: A total of 45 neonates were enrolled in the study group and 32 were enrolled in the control group. On day 1, the diversity and richness of the microflora of the study group were more than those of the control group. Non-metric multidimensional scaling analysis showed significant differences in the microbiota of the two groups on days 1, 3, and 5. At the phylum level, the main microflora of the two groups were not different. At the genus level, the study group had increased relative abundance of Clostridium_sensu_stricto_1, Lachnoclostridium, Fusicatenibacter, etc. on day 1. On day 3, the relative abundance of Clostridium_sensu_stricto_1, Fusicatenibacter, etc. was still greater than that of the control group, and the relative abundance of Staphylococcus was less than that of the control group. On day 5, the relative abundance of Clostridium_sensu_stricto_1 and Lachnoclostridium was still higher than that of the control group, and the relative abundance of Dubosiella in the study group was significantly increased. At the species level, on day 3, the relative abundance of Staphylococcus caprae in the study group was less than that in the control group. Linear discriminant analysis effect size showed that the microbiota of the study group mainly consisted of Lachnospiraceae and Clostridia on day 1 and Clostridia on day 3. In the control group, Staphylococcus was the dominant bacterium on day 3. Neonates in the study group were followed up for 6 months, and the communication score of ASQ-3 was negatively correlated with the relative abundance of Lachnospiraceae and Clostridia on day 1. Conclusion: The diversity and richness of the microbiota of asphyxiated neonates on the first day of life were significantly increased and mainly consisted of pathogenic flora. Lachnospiraceae and Clostridia found in neonates with asphyxia on day 1 of life may be related to neural development at 6 months.
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Affiliation(s)
| | | | | | - Ying Han
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Xinlin Hou
- Department of Pediatrics, Peking University First Hospital, Beijing, China
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Cheng X, Zheng J, Lin A, Xia H, Zhang Z, Gao Q, Lv W, Liu H. A review: Roles of carbohydrates in human diseases through regulation of imbalanced intestinal microbiota. J Funct Foods 2020. [DOI: 10.1016/j.jff.2020.104197] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Clinical Response and Changes of Cytokines and Zonulin Levels in Patients with Diarrhoea-Predominant Irritable Bowel Syndrome Treated with Bifidobacterium Longum ES1 for 8 or 12 Weeks: A Preliminary Report. J Clin Med 2020; 9:jcm9082353. [PMID: 32717980 PMCID: PMC7464152 DOI: 10.3390/jcm9082353] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 07/21/2020] [Accepted: 07/22/2020] [Indexed: 12/12/2022] Open
Abstract
Bifidobacterium longum (B. longum) ES1 is a probiotic strain capable of modulating microbiome composition, anti-inflammatory activity and intestinal barrier function. We investigated the use of B. Longum ES1 in the treatment of patients with diarrhoea-predominant irritable bowel syndrome (IBS-D). Sixteen patients were treated for 8 or 12 weeks with B. Longum ES1 (1 × 109 CFU/day). Serum zonulin and cytokines were measured at baseline (T0) and at the end of therapy (T1). Clinical response to therapy was assessed by IBS Severity Scoring System. Interleukin (IL)-6, IL-8, IL-12p70 and tumor necrosis factor (TNF) α levels decreased from T0 to T1, irrespective of treatment duration (p < 0.05), while zonulin levels diminished only in patients treated for 12 weeks (p = 0.036). Clinical response was observed in 5/16 patients (31%): 4/8 (50%) treated for 12 weeks and 1/8 (13%) treated for 8 weeks. Abdominal pain improved only in patients treated for 12 weeks (5/8 vs. 0/8, p = 0.025), while stool consistency improved regardless of therapy duration (p < 0.001). In conclusion, the results of this pilot study showed, in IBS-D patients treated for 12 weeks with B. longum ES1, a reduction in the levels of pro-inflammatory cytokines, and intestinal permeability as well as an improvement in gastrointestinal symptoms, but further studies including a placebo-control group are necessary to prove a causal link.
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10
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Halkjaer SI, Lo B, Cold F, Christensen AHH, Gluud LL, Petersen AM. Fecal microbiota transplantation for treatment of irritable bowel syndrome. Hippokratia 2020. [DOI: 10.1002/14651858.cd013602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Sofie I Halkjaer
- Gastrounit, Medical Division; Copenhagen University Hospital Hvidovre; Hvidovre Denmark
| | - Bobby Lo
- Gastrounit, Medical Division; Copenhagen University Hospital Hvidovre; Hvidovre Denmark
| | - Frederik Cold
- Gastrounit, Medical Division; Copenhagen University Hospital Hvidovre; Hvidovre Denmark
- Aleris-Hamlet Hospitals Copenhagen; Søborg Denmark
| | | | - Lise Lotte Gluud
- Gastrounit, Medical Division; Copenhagen University Hospital Hvidovre; Hvidovre Denmark
| | - Andreas M Petersen
- Gastrounit, Medical Division; Copenhagen University Hospital Hvidovre; Hvidovre Denmark
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11
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Meydan C, Afshinnekoo E, Rickard N, Daniels G, Kunces L, Hardy T, Lili L, Pesce S, Jacobson P, Mason CE, Dudley J, Zhang B. Improved gastrointestinal health for irritable bowel syndrome with metagenome-guided interventions. PRECISION CLINICAL MEDICINE 2020; 3:136-146. [PMID: 32685241 PMCID: PMC7327130 DOI: 10.1093/pcmedi/pbaa013] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 04/15/2020] [Accepted: 04/19/2020] [Indexed: 12/13/2022] Open
Abstract
Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder worldwide, and the most common reason for referral to gastroenterology clinics. However, the pathophysiology is still not fully understood and consequently current management guidelines are very symptom-specific, leading to mixed results. Here we present a study of 88 individuals with IBS who had baseline sequencing of their gut microbiome (stool samples), received targeted interventions that included dietary, supplement, prebiotic/probiotic, and lifestyle recommendations for a 30-day period, and a follow-up sequencing of their gut microbiome. The study's objectives were to demonstrate unique metagenomic signatures across the IBS phenotypes and to validate whether metagenomic-guided interventions could lead to improvement of symptom scores in individuals with IBS. Enrolled subjects also completed a baseline and post-intervention questionnaire that assessed their symptom scores. The average symptom score of an individual with IBS at baseline was 160 and at the endpoint of the study the average symptom score of the cohort was 100.9. The mixed IBS subtype showed the most significant reduction in symptom scores across the different subtypes (average decrease by 102 points, P = 0.005). The metagenomics analysis reveals shifts in the microbiome post-intervention that have been cross-validated with the literature as being associated with improvement of IBS symptoms. Given the complex nature of IBS, further studies with larger sample sizes, more targeted analyses, and a broader population cohort are needed to explore these results further.
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Affiliation(s)
- Cem Meydan
- Onegevity Health, 152 W 57th, New York, NY 10019, USA
| | | | - Nate Rickard
- Onegevity Health, 152 W 57th, New York, NY 10019, USA
| | - Guy Daniels
- Onegevity Health, 152 W 57th, New York, NY 10019, USA
| | - Laura Kunces
- Onegevity Health, 152 W 57th, New York, NY 10019, USA
| | - Theresa Hardy
- Onegevity Health, 152 W 57th, New York, NY 10019, USA
| | - Loukia Lili
- Onegevity Health, 152 W 57th, New York, NY 10019, USA
| | - Sarah Pesce
- Onegevity Health, 152 W 57th, New York, NY 10019, USA
| | - Paul Jacobson
- Onegevity Health, 152 W 57th, New York, NY 10019, USA
| | | | - Joel Dudley
- Onegevity Health, 152 W 57th, New York, NY 10019, USA
| | - Bodi Zhang
- Onegevity Health, 152 W 57th, New York, NY 10019, USA
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Does Irritable Bowel Syndrome Exist? Identifiable and Treatable Causes of Associated Symptoms Suggest It May Not. GASTROINTESTINAL DISORDERS 2019. [DOI: 10.3390/gidisord1030027] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Significant shortcomings in irritable bowel syndrome (IBS) diagnosis and treatment may arise from IBS being an “umbrella” diagnosis that clusters several underlying identifiable and treatable causes for the same symptom presentation into one classification. This view is compatible with the emerging understanding that the pathophysiology of IBS is heterogeneous with varied disease mechanisms responsible for the central pathological features. Collectively, these converging views of the pathophysiology, assessment and management of IBS render the traditional diagnosis and treatment of IBS less relevant; in fact, they suggest that IBS is not a disease entity per se and posit the question “does IBS exist?” The aim of this narrative review is to explore identifiable and treatable causes of digestive symptoms, including lifestyle, environmental and nutritional factors, as well as underlying functional imbalances, that may be misinterpreted as being IBS.
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Duan R, Zhu S, Wang B, Duan L. Alterations of Gut Microbiota in Patients With Irritable Bowel Syndrome Based on 16S rRNA-Targeted Sequencing: A Systematic Review. Clin Transl Gastroenterol 2019; 10:e00012. [PMID: 30829919 PMCID: PMC6407812 DOI: 10.14309/ctg.0000000000000012] [Citation(s) in RCA: 105] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Accepted: 01/02/2019] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Alterations of gut microbiota have been thought to be associated with irritable bowel syndrome (IBS). Many studies have reported significant alterations of gut microbiota in patients with IBS based on 16S ribosomal RNA-targeted sequencing. However, results from these studies are inconsistent or even contradictory. We performed a systematic review to explore the alterations of gut microbiota in patients with IBS compared with healthy controls (HCs). METHODS The databases PubMed, Cochrane Library, Web of Science, and Embase were searched for studies published until February 28, 2018, for case-control studies detecting gut microbiota in patients with IBS. Methodological quality was assessed using the Newcastle-Ottawa Scale. The α-diversity and alterations of gut microbiota in patients with IBS compared with HCs were analyzed. RESULTS Sixteen articles involving 777 patients with IBS and 461 HCs were included. Quality assessment scores of the studies ranged from 5 to 7. For most studies, patients with IBS had a lower α-diversity than HCs in both fecal and mucosal samples. Relatively consistent changes in fecal microbiota for patients with IBS included increased Firmicutes, decreased Bacteroidetes, and increased Firmicutes:Bacteroidetes ratio at the phylum level, as well as increased Clostridia and Clostridiales, decreased Bacteroidia and Bacteroidales at lower taxonomic levels. Results for mucosal microbiota were inconsistent. CONCLUSIONS Alterations of gut microbiota exist in patients with IBS and have significant association with the development of IBS. Further studies are needed to draw conclusions about gut microbiota changes in patients with IBS. TRANSLATIONAL IMPACT This knowledge might improve the understanding of microbial signatures in patients with IBS and would guide future therapeutic strategies.
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Affiliation(s)
- Ruqiao Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Shiwei Zhu
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Ben Wang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Liping Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
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Abstract
The gut microbiota is a crucial actor in human physiology. Many of these effects are mediated by metabolites that are either produced by the microbes or derived from the transformation of environmental or host molecules. Among the array of metabolites at the interface between these microorganisms and the host is the essential aromatic amino acid tryptophan (Trp). In the gut, the three major Trp metabolism pathways leading to serotonin (5-hydroxytryptamine), kynurenine (Kyn), and indole derivatives are under the direct or indirect control of the microbiota. In this review, we gather the most recent advances concerning the central role of Trp metabolism in microbiota-host crosstalk in health and disease. Deciphering the complex equilibrium between these pathways will facilitate a better understanding of the pathogenesis of human diseases and open therapeutic opportunities.
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