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Chen Y, Wu N, Yan X, Kang L, Ou G, Zhou Z, Xu C, Feng J, Shi T. Impact of gut microbiota on colorectal anastomotic healing (Review). Mol Clin Oncol 2025; 22:52. [PMID: 40297498 PMCID: PMC12035527 DOI: 10.3892/mco.2025.2847] [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: 12/20/2024] [Accepted: 03/27/2025] [Indexed: 04/30/2025] Open
Abstract
Intestinal anastomosis is a critical procedure in both emergency and elective surgeries to maintain intestinal continuity. However, the incidence of anastomotic leakage (AL) has recently increased, reaching up to 20%, imposing major clinical and economic burdens. Substantial perioperative alterations in the intestinal microbiota composition may contribute to AL, particularly due to disruptions in key microbial populations essential for intestinal health and healing. The intricate interplay between the intestinal microbiota and the host immune system, along with microbial changes before and during surgery, significantly influences anastomotic integrity. Notably, specific pathogens such as Enterococcus and Pseudomonas aeruginosa have been implicated in AL pathogenesis. Preventive strategies including dietary regulation, personalized intestinal preparation, microbiota restoration and enhanced recovery after surgery protocols, may mitigate AL risks. Future research should focus on elucidating the precise mechanisms linking intestinal microbiota alterations to anastomotic healing and developing targeted interventions to improve surgical outcomes.
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Affiliation(s)
- Yangyang Chen
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Nian Wu
- Clinical Medical College, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
| | - Xin Yan
- Anesthesia Operating Room, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Liping Kang
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Guoyong Ou
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Zhenlin Zhou
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Changbo Xu
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Jiayi Feng
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Tou Shi
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
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El Jaddaoui I, Sehli S, Al Idrissi N, Bakri Y, Belyamani L, Ghazal H. The Gut Mycobiome for Precision Medicine. J Fungi (Basel) 2025; 11:279. [PMID: 40278100 PMCID: PMC12028274 DOI: 10.3390/jof11040279] [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: 03/08/2025] [Revised: 03/29/2025] [Accepted: 03/31/2025] [Indexed: 04/26/2025] Open
Abstract
The human gastrointestinal tract harbors a vast array of microorganisms, which play essential roles in maintaining metabolic balance and immune function. While bacteria dominate the gut microbiome, fungi represent a much smaller, often overlooked fraction. Despite their relatively low abundance, fungi may significantly influence both health and disease. Advances in next-generation sequencing, metagenomics, metatranscriptomics, metaproteomics, metabolomics, and computational biology have provided novel opportunities to study the gut mycobiome, shedding light on its composition, functional genes, and metabolite interactions. Emerging evidence links fungal dysbiosis to various diseases, including inflammatory bowel disease, colorectal cancer, metabolic disorders, and neurological conditions. The gut mycobiome also presents a promising avenue for precision medicine, particularly in biomarker discovery, disease diagnostics, and targeted therapeutics. Nonetheless, significant challenges remain in effectively integrating gut mycobiome knowledge into clinical practice. This review examines gut fungal microbiota, highlighting analytical methods, associations with human diseases, and its potential role in precision medicine. It also discusses pathways for clinical translation, particularly in diagnosis and treatment, while addressing key barriers to implementation.
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Affiliation(s)
- Islam El Jaddaoui
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, University Mohammed V, Rabat 10000, Morocco; (I.E.J.); (Y.B.)
- Genomic Center of Human Pathologies, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat 10000, Morocco
- Laboratory of Precision Medicine & One Health (MedPreOne), School of Medicine, Mohammed VI University of Sciences & Health, Casablanca 82403, Morocco; (S.S.); (N.A.I.)
| | - Sofia Sehli
- Laboratory of Precision Medicine & One Health (MedPreOne), School of Medicine, Mohammed VI University of Sciences & Health, Casablanca 82403, Morocco; (S.S.); (N.A.I.)
| | - Najib Al Idrissi
- Laboratory of Precision Medicine & One Health (MedPreOne), School of Medicine, Mohammed VI University of Sciences & Health, Casablanca 82403, Morocco; (S.S.); (N.A.I.)
| | - Youssef Bakri
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, University Mohammed V, Rabat 10000, Morocco; (I.E.J.); (Y.B.)
- Genomic Center of Human Pathologies, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat 10000, Morocco
| | - Lahcen Belyamani
- School of Medicine, Mohammed VI University of Sciences & Health, Casablanca 82403, Morocco;
| | - Hassan Ghazal
- Laboratory of Precision Medicine & One Health (MedPreOne), School of Medicine, Mohammed VI University of Sciences & Health, Casablanca 82403, Morocco; (S.S.); (N.A.I.)
- Laboratory of Sports Sciences and Performance Optimization, Royal Institute of Executive Management, Salé 10102, Morocco
- National Center for Scientific and Technical Research, Rabat 10102, Morocco
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Hao Z, Lu Y, Hao Y, Luo Y, Wu K, Zhu C, Shi P, Zhu F, Lin Y, Zeng X. Fungal mycobiome dysbiosis in choledocholithiasis concurrent with cholangitis. J Gastroenterol 2025; 60:340-355. [PMID: 39604579 DOI: 10.1007/s00535-024-02183-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 11/11/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND The gut mycobiome might have an important influence on the pathogenesis of choledocholithiasis concurrent with cholangitis (CC). The aim of this study was to characterize the fungal mycobiome profiles, explore the correlation and equilibrium of gut interkingdom network among bacteria-fungi-metabolites triangle in CCs. METHODS In a retrospective case-control study, we recruited patients with CC (n = 25) and healthy controls (HCs) (n = 25) respectively to analyze the gut fungal dysbiosis. Metagenomic sequencing was employed to characterize the gut mycobiome profiles, and liquid chromatography/mass spectrometry (LC/MS) analysis was used to quantify the metabolites composition. RESULTS The Shannon index displayed a reduction in fungal α-diversity in CCs compared to HCs (p = 0.041), and the overall fungal composition differed significantly between two groups. The dominant 7 fungi species with the remarkable altered abundance were identified (LDA score > 3.0, p < 0.05), including CC-enriched Aspergillus_niger and CC-depleted fungi Saccharomyces_boulardii. In addition, the correlations between CC-related fungi and clinical variables in CCs were analyzed. Moreover, the increased abundance ratio of Basidiomycota-to-Ascomycota and a dense linkage of bacteria-fungi interkingdom network in CCs were demonstrated. Finally, we identified 30 markedly altered metabolites in CCs (VIP > 1.0 and p < 0.05), including low level of acetate and butyrate, and the deeper understanding on the complexity of bacteria-fungi-metabolites triangle involving bile inflammation was verified. CONCLUSION Our investigation demonstrated a distinct gut fungal dysbiosis in CCs and proposed that, beyond bacteria, the more attention should be paid to significantly potential influence of fungi and bacteria-fungi-metabolites triangle interkingdom interactions on pathogenesis of CC.
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Affiliation(s)
- Zhiyuan Hao
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China
| | - Yiting Lu
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China
| | - Yarong Hao
- Department of Gastroenterology, Shanghai Changzheng Hospital, Navy Military Medical University, 415 Fengyang Road, Shanghai, 200003, China
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China
| | - Yuanyuan Luo
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China
| | - Kaiming Wu
- Department of Gastroenterology, Shanghai Changzheng Hospital, Navy Military Medical University, 415 Fengyang Road, Shanghai, 200003, China
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China
| | - Changpeng Zhu
- Department of Gastroenterology, Shanghai Changzheng Hospital, Navy Military Medical University, 415 Fengyang Road, Shanghai, 200003, China
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China
| | - Peimei Shi
- Department of Gastroenterology, Shanghai Changzheng Hospital, Navy Military Medical University, 415 Fengyang Road, Shanghai, 200003, China
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China
| | - Feng Zhu
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China
| | - Yong Lin
- Department of Gastroenterology, Shanghai Changzheng Hospital, Navy Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China.
| | - Xin Zeng
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China.
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China.
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Guglietta S, Li X, Saxena D. Role of Fungi in Tumorigenesis: Promises and Challenges. ANNUAL REVIEW OF PATHOLOGY 2025; 20:459-482. [PMID: 39854185 DOI: 10.1146/annurev-pathmechdis-111523-023524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/26/2025]
Abstract
The mycobiome plays a key role in the host immune responses in homeostasis and inflammation. Recent studies suggest that an imbalance in the gut's fungi contributes to chronic, noninfectious diseases such as obesity, metabolic disorders, and cancers. Pathogenic fungi can colonize specific organs, and the gut mycobiome has been linked to the development and progression of various cancers, including colorectal, breast, head and neck, and pancreatic cancers. Some fungal species can promote tumorigenesis by triggering the complement system. However, in immunocompromised patients, fungi can also inhibit this activation and establish life-threatening infections. Interestingly, the interaction of the fungi and bacteria can also induce unique host immune responses. Recent breakthroughs and advancements in high-throughput sequencing of the gut and tumor mycobiomes are highlighting novel diagnostic and therapeutic opportunities for cancer. We discuss the latest developments in the field of cancer and the mycobiome and the potential benefits and challenges of antifungal therapies.
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Affiliation(s)
- Silvia Guglietta
- Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina, USA
- Hollings Cancer Center, Charleston, South Carolina, USA
| | - Xin Li
- Department of Molecular Pathobiology, NYU College of Dentistry, New York, NY, USA;
- Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY, USA
- Department of Urology, NYU Grossman School of Medicine, New York, NY, USA
| | - Deepak Saxena
- Department of Molecular Pathobiology, NYU College of Dentistry, New York, NY, USA;
- Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY, USA
- Department of Surgery, NYU Grossman School of Medicine, New York, NY, USA
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Lianos GD, Frountzas M, Kyrochristou ID, Sakarellos P, Tatsis V, Kyrochristou GD, Bali CD, Gazouli M, Mitsis M, Schizas D. What Is the Role of the Gut Microbiota in Anastomotic Leakage After Colorectal Resection? A Scoping Review of Clinical and Experimental Studies. J Clin Med 2024; 13:6634. [PMID: 39597778 PMCID: PMC11594793 DOI: 10.3390/jcm13226634] [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: 10/20/2024] [Revised: 11/03/2024] [Accepted: 11/04/2024] [Indexed: 11/29/2024] Open
Abstract
Background: Anastomotic leakage (AL) still remains a common complication after colorectal anastomosis that leads to increased morbidity and mortality. The gut microbiota has been hypothesized as one of the risk factors associated with anastomotic leakage. The aim of the present study was to summarize all existing clinical and experimental studies that evaluate the impact of intestinal microbiota on anastomotic leakage after colorectal resection. Methods: The present scoping review was designed according to PRISMA recommendations and a systematic search in Medline, Scopus, EMBASE, Clinicaltrials.gov, Google Scholar, and CENTRAL was conducted until September 2024. Results: Overall, 7 clinical and 5 experimental studies were included. A diminished α-diversity of the gut microbiota in patients suffering from AL was demonstrated. Specific microbe genera, such as Lachnospiraceae, Bacteroidaceae, Bifidobacterium, Acinetobacter, Fusobacterium, Dielma, Elusimicronium, Prevotella, and Faecalibacterium, seem to be associated with AL. However, specific genera, like Prevotella, Streptococcus, Eubacterium, Enterobacteriaceae, Klebsiella, Actinobacteria, Gordonibacter, Phocaeicola, and Ruminococcus2, seem to be protective against AL. Experimental studies highlighted that the Western diet seems to affect microbiota diversity and increases the AL rate, whereas anastomotic healing seems to be impaired by high metalloproteinase production and increased collagenase activity. Conclusions: The intestinal microbiota seems to play an important role in anastomotic leakage after colorectal resection. Specific interventions targeting the microbiota's composition and the pathophysiological mechanisms by which it impairs anastomotic healing could diminish the risk for anastomotic leakage and improve clinical outcomes. However, future studies should be based on prospective design and eliminate heterogeneity.
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Affiliation(s)
- Georgios D. Lianos
- Department of Surgery, University Hospital of Ioannina, 45110 Ioannina, Greece; (G.D.L.); (I.D.K.); (V.T.); (G.D.K.); (C.D.B.); (M.M.)
| | - Maximos Frountzas
- First Propaedeutic Department of Surgery, Hippocration General Hospital, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Ilektra D. Kyrochristou
- Department of Surgery, University Hospital of Ioannina, 45110 Ioannina, Greece; (G.D.L.); (I.D.K.); (V.T.); (G.D.K.); (C.D.B.); (M.M.)
| | - Panagiotis Sakarellos
- First Department of Surgery, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece; (P.S.); (D.S.)
| | - Vasileios Tatsis
- Department of Surgery, University Hospital of Ioannina, 45110 Ioannina, Greece; (G.D.L.); (I.D.K.); (V.T.); (G.D.K.); (C.D.B.); (M.M.)
| | - Gerasimia D. Kyrochristou
- Department of Surgery, University Hospital of Ioannina, 45110 Ioannina, Greece; (G.D.L.); (I.D.K.); (V.T.); (G.D.K.); (C.D.B.); (M.M.)
| | - Christina D. Bali
- Department of Surgery, University Hospital of Ioannina, 45110 Ioannina, Greece; (G.D.L.); (I.D.K.); (V.T.); (G.D.K.); (C.D.B.); (M.M.)
| | - Maria Gazouli
- Laboratory of Biology, Department of Basic Medical Sciences, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece;
| | - Michail Mitsis
- Department of Surgery, University Hospital of Ioannina, 45110 Ioannina, Greece; (G.D.L.); (I.D.K.); (V.T.); (G.D.K.); (C.D.B.); (M.M.)
| | - Dimitrios Schizas
- First Department of Surgery, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece; (P.S.); (D.S.)
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Youn HY, Kim HJ, Kim H, Seo KH. A comparative evaluation of the kefir yeast Kluyveromyces marxianus A4 and sulfasalazine in ulcerative colitis: anti-inflammatory impact and gut microbiota modulation. Food Funct 2024; 15:6717-6730. [PMID: 38833212 DOI: 10.1039/d4fo00427b] [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: 06/06/2024]
Abstract
Although only Saccharomyces boulardii has been studied for ulcerative colitis (UC), probiotic yeasts have immense therapeutic potential. Herein, we evaluated the kefir yeast Kluyveromyces marxianus A4 (Km A4) and its anti-inflammatory effect with sulfasalazine in BALB/c mice with dextran sulfate sodium (DSS)-induced colitis. Oral administration continued for 7 days after the mice were randomly divided into seven groups: control (CON, normal mice administered with saline), DSS-induced colitis mice administered saline (DSS), and DSS-induced colitis mice administered sulfasalazine only (S), Km A4 only (A4), Km A4 plus sulfasalazine (A4 + S), S. boulardii ATCC MYA-796 (Sb MYA-796) only (Sb), and Sb MYA-796 plus sulfasalazine (Sb + S). The β-glucan content of Km A4 was significantly higher than that of Sb MYA-796 (P < 0.05). Body weight gain (BWG) significantly correlated with colon length, cyclooxygenase-2 (Cox-2) levels, and Bacteroides abundance (P < 0.05). In colitis-induced mice, the A4 + S group had the lowest histological score (6.00) compared to the DSS group (12.67), indicating the anti-inflammatory effects of this combination. The A4 + S group showed significantly downregulated expression of interleukin (Il)-6, tumor necrosis factor-α (Tnf-α), and Cox-2 and upregulated expression of Il-10 and occludin (Ocln) compared to the DSS group. Mice treated with A4 + S had enhanced Bacteroides abundance in their gut microbiota compared with the DSS group (P < 0.05). Bacteroides were significantly correlated with all colitis biomarkers (BWG, colon length, Il-6, Tnf-α, Il-10, Cox-2, and Ocln; P < 0.05). The anti-inflammatory effects of Km A4 could be attributed to high β-glucan content and gut microbiota modulation. Thus, treatment with Km A4 and sulfasalazine could alleviate UC.
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Affiliation(s)
- Hye-Young Youn
- Center for One Health, Department of Veterinary Public Health, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, South Korea
| | - Hyeon-Jin Kim
- Center for One Health, Department of Veterinary Public Health, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, South Korea
| | - Hyunsook Kim
- Department of Food & Nutrition, College of Human Ecology, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, South Korea
| | - Kun-Ho Seo
- Center for One Health, Department of Veterinary Public Health, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, South Korea
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D'Antongiovanni V, Antonioli L, Benvenuti L, Pellegrini C, Di Salvo C, Calvigioni M, Panattoni A, Ryskalin L, Natale G, Banni S, Carta G, Ghelardi E, Fornai M. Use of Saccharomyces boulardii CNCM I-745 as therapeutic strategy for prevention of nonsteroidal anti-inflammatory drug-induced intestinal injury. Br J Pharmacol 2023; 180:3215-3233. [PMID: 37519261 DOI: 10.1111/bph.16200] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 02/21/2023] [Accepted: 03/28/2023] [Indexed: 08/01/2023] Open
Abstract
BACKGROUND AND PURPOSE Nonsteroidal anti-inflammatory drugs (NSAIDs) can be associated with severe adverse digestive effects. This study examined the protective effects of the probiotic Saccharomyces boulardii CNCM I-745 in a rat model of diclofenac-induced enteropathy. EXPERIMENTAL APPROACH Enteropathy was induced in 40-week-old male rats by intragastric diclofenac (4 mg·kg-1 BID for 14 days). S. boulardii CNCM I-745 (3 g·kg-1 BID by oral gavage) was administered starting 14 days before (preventive protocol) or along with (curative protocol) diclofenac administration. Ileal damage, inflammation, barrier integrity, gut microbiota composition and toll-like receptors (TLRs)-nuclear factor κB (NF-κB) pathway were evaluated. KEY RESULTS Diclofenac elicited intestinal damage, along with increments of myeloperoxidase, malondialdehyde, tumour necrosis factor and interleukin-1β, overexpression of TLR2/4, myeloid differentiation primary response 88 (Myd88) and NF-κB p65, increased faecal calprotectin and butyrate levels, and decreased blood haemoglobin levels, occludin and butyrate transporter monocarboxylate transporter 1 (MCT1) expression. In addition, diclofenac provoked a shift of bacterial taxa in both faecal and ileal samples. Treatment with S. boulardii CNCM I-745, in both preventive and curative protocols, counteracted the majority of these deleterious changes. Only preventive administration of the probiotic counteracted NSAID-induced decreased expression of MCT1 and increase in faecal butyrate levels. Occludin expression, after probiotic treatment, did not significantly change. CONCLUSIONS AND IMPLICATIONS Treatment with S. boulardii CNCM I-745 prevents diclofenac-induced enteropathy through anti-inflammatory and antioxidant activities. Such effects are likely to be related to increased tissue butyrate bioavailability, through an improvement of butyrate uptake by the enteric mucosa.
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Affiliation(s)
| | - Luca Antonioli
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Laura Benvenuti
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Carolina Pellegrini
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Clelia Di Salvo
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Marco Calvigioni
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Adelaide Panattoni
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Larisa Ryskalin
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Gianfranco Natale
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Sebastiano Banni
- Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
| | - Gianfranca Carta
- Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
| | - Emilia Ghelardi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Matteo Fornai
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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Lopes SA, Roque-Borda CA, Duarte JL, Di Filippo LD, Borges Cardoso VM, Pavan FR, Chorilli M, Meneguin AB. Delivery Strategies of Probiotics from Nano- and Microparticles: Trends in the Treatment of Inflammatory Bowel Disease-An Overview. Pharmaceutics 2023; 15:2600. [PMID: 38004578 PMCID: PMC10674632 DOI: 10.3390/pharmaceutics15112600] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 10/24/2023] [Accepted: 10/27/2023] [Indexed: 11/26/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, most known as ulcerative colitis (UC) and Crohn's disease (CD), that affects the gastrointestinal tract (GIT), causing considerable symptoms to millions of people around the world. Conventional therapeutic strategies have limitations and side effects, prompting the exploration of innovative approaches. Probiotics, known for their potential to restore gut homeostasis, have emerged as promising candidates for IBD management. Probiotics have been shown to minimize disease symptoms, particularly in patients affected by UC, opening important opportunities to better treat this disease. However, they exhibit limitations in terms of stability and targeted delivery. As several studies demonstrate, the encapsulation of the probiotics, as well as the synthetic drug, into micro- and nanoparticles of organic materials offers great potential to solve this problem. They resist the harsh conditions of the upper GIT portions and, thus, protect the probiotic and drug inside, allowing for the delivery of adequate amounts directly into the colon. An overview of UC and CD, the benefits of the use of probiotics, and the potential of micro- and nanoencapsulation technologies to improve IBD treatment are presented. This review sheds light on the remarkable potential of nano- and microparticles loaded with probiotics as a novel and efficient strategy for managing IBD. Nonetheless, further investigations and clinical trials are warranted to validate their long-term safety and efficacy, paving the way for a new era in IBD therapeutics.
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Affiliation(s)
- Sílvio André Lopes
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, Sao Paulo State University (UNESP), Araraquara 14800-903, Brazil; (S.A.L.); (J.L.D.); (L.D.D.F.); (V.M.B.C.); (F.R.P.); (M.C.)
| | | | - Jonatas Lobato Duarte
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, Sao Paulo State University (UNESP), Araraquara 14800-903, Brazil; (S.A.L.); (J.L.D.); (L.D.D.F.); (V.M.B.C.); (F.R.P.); (M.C.)
| | - Leonardo Delello Di Filippo
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, Sao Paulo State University (UNESP), Araraquara 14800-903, Brazil; (S.A.L.); (J.L.D.); (L.D.D.F.); (V.M.B.C.); (F.R.P.); (M.C.)
| | - Vinícius Martinho Borges Cardoso
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, Sao Paulo State University (UNESP), Araraquara 14800-903, Brazil; (S.A.L.); (J.L.D.); (L.D.D.F.); (V.M.B.C.); (F.R.P.); (M.C.)
| | - Fernando Rogério Pavan
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, Sao Paulo State University (UNESP), Araraquara 14800-903, Brazil; (S.A.L.); (J.L.D.); (L.D.D.F.); (V.M.B.C.); (F.R.P.); (M.C.)
| | - Marlus Chorilli
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, Sao Paulo State University (UNESP), Araraquara 14800-903, Brazil; (S.A.L.); (J.L.D.); (L.D.D.F.); (V.M.B.C.); (F.R.P.); (M.C.)
| | - Andréia Bagliotti Meneguin
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, Sao Paulo State University (UNESP), Araraquara 14800-903, Brazil; (S.A.L.); (J.L.D.); (L.D.D.F.); (V.M.B.C.); (F.R.P.); (M.C.)
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Menni A, Moysidis M, Tzikos G, Stavrou G, Tsetis JK, Shrewsbury AD, Filidou E, Kotzampassi K. Looking for the Ideal Probiotic Healing Regime. Nutrients 2023; 15:3055. [PMID: 37447381 PMCID: PMC10346906 DOI: 10.3390/nu15133055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 06/30/2023] [Accepted: 07/05/2023] [Indexed: 07/15/2023] Open
Abstract
Wound healing is a multi-factorial response to tissue injury, aiming to restore tissue continuity. Numerous recent experimental and clinical studies clearly indicate that probiotics are applied topically to promote the wound-healing process. However, the precise mechanism by which they contribute to healing is not yet clear. Each strain appears to exert a distinctive, even multi-factorial action on different phases of the healing process. Given that a multi-probiotic formula exerts better results than a single strain, the pharmaceutical industry has embarked on a race for the production of a formulation containing a combination of probiotics capable of playing a role in all the phases of the healing process. Hence, the object of this review is to describe what is known to date of the distinctive mechanisms of each of the most studied probiotic strains in order to further facilitate research toward the development of combinations of strains and doses, covering the whole spectrum of healing. Eleven probiotic species have been analyzed, the only criterion of inclusion being a minimum of two published research articles.
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Affiliation(s)
- Alexandra Menni
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece (M.M.); (G.T.); (A.D.S.)
| | - Moysis Moysidis
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece (M.M.); (G.T.); (A.D.S.)
| | - Georgios Tzikos
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece (M.M.); (G.T.); (A.D.S.)
| | - George Stavrou
- Department of Colorectal Surgery, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK;
| | | | - Anne D. Shrewsbury
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece (M.M.); (G.T.); (A.D.S.)
| | - Eirini Filidou
- Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece;
| | - Katerina Kotzampassi
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece (M.M.); (G.T.); (A.D.S.)
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10
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Cela L, Brindisi G, Gravina A, Pastore F, Semeraro A, Bringheli I, Marchetti L, Morelli R, Cinicola B, Capponi M, Gori A, Pignataro E, Piccioni MG, Zicari AM, Anania C. Molecular Mechanism and Clinical Effects of Probiotics in the Management of Cow's Milk Protein Allergy. Int J Mol Sci 2023; 24:9781. [PMID: 37372929 DOI: 10.3390/ijms24129781] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 05/23/2023] [Accepted: 05/31/2023] [Indexed: 06/29/2023] Open
Abstract
Cow's milk protein allergy (CMPA) is the most common food allergy (FA) in infancy, affecting approximately 2% of children under 4 years of age. According to recent studies, the increasing prevalence of FAs can be associated with changes in composition and function of gut microbiota or "dysbiosis". Gut microbiota regulation, mediated by probiotics, may modulate the systemic inflammatory and immune responses, influencing the development of allergies, with possible clinical benefits. This narrative review collects the actual evidence of probiotics' efficacy in the management of pediatric CMPA, with a specific focus on the molecular mechanisms of action. Most studies included in this review have shown a beneficial effect of probiotics in CMPA patients, especially in terms of achieving tolerance and improving symptoms.
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Affiliation(s)
- Ludovica Cela
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Giulia Brindisi
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Alessandro Gravina
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Francesca Pastore
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Antonio Semeraro
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Ivana Bringheli
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Lavinia Marchetti
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Rebecca Morelli
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Bianca Cinicola
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Martina Capponi
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Alessandra Gori
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Elia Pignataro
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Maria Grazia Piccioni
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Anna Maria Zicari
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Caterina Anania
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
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11
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Abstract
The microbiome may impact cancer development, progression and treatment responsiveness, but its fungal components remain insufficiently studied in this context. In this review, we highlight accumulating evidence suggesting a possible involvement of commensal and pathogenic fungi in modulation of cancer-related processes. We discuss the mechanisms by which fungi can influence tumour biology, locally by activity exerted within the tumour microenvironment, or remotely through secretion of bioactive metabolites, modulation of host immunity and communications with neighbouring bacterial commensals. We examine prospects of utilising fungi-related molecular signatures in cancer diagnosis, patient stratification and assessment of treatment responsiveness, while highlighting challenges and limitations faced in performing such research. In all, we demonstrate that fungi likely constitute important members of mucosal and tumour-residing microbiomes. Exploration of fungal inter-kingdom interactions with the bacterial microbiome and the host and decoding of their causal impacts on tumour biology may enable their harnessing into cancer diagnosis and treatment.
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Affiliation(s)
- Aurelia Saftien
- Microbiome and Cancer Division, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Faculty of Biosciences, Heidelberg University, Heidelberg, Germany
| | - Jens Puschhof
- Microbiome and Cancer Division, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Eran Elinav
- Microbiome and Cancer Division, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel
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12
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Xu X, Wu J, Jin Y, Huang K, Zhang Y, Liang Z. Both Saccharomyces boulardii and Its Postbiotics Alleviate Dextran Sulfate Sodium-Induced Colitis in Mice, Association with Modulating Inflammation and Intestinal Microbiota. Nutrients 2023; 15:nu15061484. [PMID: 36986214 PMCID: PMC10055518 DOI: 10.3390/nu15061484] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 03/09/2023] [Accepted: 03/13/2023] [Indexed: 03/30/2023] Open
Abstract
OBJECTIVE To investigate the effect of Saccharomyces boulardii and its freeze-dried and spray-dried postbiotics on the intervention and potential mechanism of dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. [Methods] After the acclimation period of C67BL/6J mice, a colitis model was constructed by applying 2% DSS for 7 d, followed by 7 d of intervention. Subsequently, the disease activity index (DAI), organ index, colon length, colon HE staining of pathological sections, ELISA for blood inflammatory factors (Interleukin (IL)-1β, IL-6, IL-10, Tumor necrosis factor (TNF)-α), Real time quantitative polymerase chain reaction (RT-qPCR) to determine the levels of colonic inflammatory factors (IL-1β, IL-6, IL-10, TNF-α), Occludin gene expression, and intestinal flora were assessed to evaluate the protective effects of S. boulardii and its postbiotics on colitis in mice. RESULTS Compared with the DSS group, S. boulardii and the postbiotics interventions effectively improved colonic shortening and tissue damage, increased the expression of intestinal tight junction protein, reduced the secretion of pro-inflammatory factors, increased the secretion of anti-inflammatory factors, and maintained the homeostasis of intestinal microorganisms. Postbiotics intervention is better than probiotics. CONCLUSIONS S. boulardii and its postbiotics can effectively alleviate DSS-induced colitis in mice through modulating host immunity and maintaining intestinal homeostasis. Postbiotics are promising next-generation biotherapeutics for ulcerative colitis treatment.
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Affiliation(s)
- Xinge Xu
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Jingwei Wu
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Yuxin Jin
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Kunlun Huang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Yuanyuan Zhang
- Beijing Key Laboratory of Zoo Captive Wildlife Technology, Beijing 100044, China
| | - Zhihong Liang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
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13
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Liu Y, Li B, Wei Y. New understanding of gut microbiota and colorectal anastomosis leak: A collaborative review of the current concepts. Front Cell Infect Microbiol 2022; 12:1022603. [PMID: 36389160 PMCID: PMC9663802 DOI: 10.3389/fcimb.2022.1022603] [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: 08/18/2022] [Accepted: 10/06/2022] [Indexed: 01/24/2023] Open
Abstract
Anastomotic leak (AL) is a life-threatening postoperative complication following colorectal surgery, which has not decreased over time. Until now, no specific risk factors or surgical technique could be targeted to improve anastomotic healing. In the past decade, gut microbiota dysbiosis has been recognized to contribute to AL, but the exact effects are still vague. In this context, interpretation of the mechanisms underlying how the gut microbiota contributes to AL is significant for improving patients' outcomes. This review concentrates on novel findings to explain how the gut microbiota of patients with AL are altered, how the AL-specific pathogen colonizes and is enriched on the anastomosis site, and how these pathogens conduct their tissue breakdown effects. We build up a framework between the gut microbiota and AL on three levels. Firstly, factors that shape the gut microbiota profiles in patients who developed AL after colorectal surgery include preoperative intervention and surgical factors. Secondly, AL-specific pathogenic or collagenase bacteria adhere to the intestinal mucosa and defend against host clearance, including the interaction between bacterial adhesion and host extracellular matrix (ECM), the biofilm formation, and the weakened host commercial bacterial resistance. Thirdly, we interpret the potential mechanisms of pathogen-induced poor anastomotic healing.
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Affiliation(s)
- Yang Liu
- Pancreatic and Gastrointestinal Surgery Division, HwaMei Hospital, University of Chinese Academy of Science, Ningbo, China,Ningbo Clinical Research Center for Digestive System Tumors, Ningbo, China
| | - Bowen Li
- Pancreatic and Gastrointestinal Surgery Division, HwaMei Hospital, University of Chinese Academy of Science, Ningbo, China,Department of Oncology and Laparoscopy Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yunwei Wei
- Pancreatic and Gastrointestinal Surgery Division, HwaMei Hospital, University of Chinese Academy of Science, Ningbo, China,Ningbo Clinical Research Center for Digestive System Tumors, Ningbo, China,*Correspondence: Yunwei Wei,
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14
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Gamal A, Elshaer M, Alabdely M, Kadry A, McCormick TS, Ghannoum M. The Mycobiome: Cancer Pathogenesis, Diagnosis, and Therapy. Cancers (Basel) 2022; 14:2875. [PMID: 35740541 PMCID: PMC9221014 DOI: 10.3390/cancers14122875] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/06/2022] [Accepted: 06/08/2022] [Indexed: 02/01/2023] Open
Abstract
Cancer is among the leading causes of death globally. Despite advances in cancer research, a full understanding of the exact cause has not been established. Recent data have shown that the microbiome has an important relationship with cancer on various levels, including cancer pathogenesis, diagnosis and prognosis, and treatment. Since most studies have focused only on the role of bacteria in this process, in this article we review the role of fungi-another important group of the microbiome, the totality of which is referred to as the "mycobiome"-in the development of cancer and how it can impact responses to anticancer medications. Furthermore, we provide recent evidence that shows how the different microbial communities interact and affect each other at gastrointestinal and non-gastrointestinal sites, including the skin, thereby emphasizing the importance of investigating the microbiome beyond bacteria.
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Affiliation(s)
- Ahmed Gamal
- Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, USA; (A.G.); (M.E.); (A.K.); (T.S.M.)
| | - Mohammed Elshaer
- Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, USA; (A.G.); (M.E.); (A.K.); (T.S.M.)
- Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Mayyadah Alabdely
- Department of Internal Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA;
| | - Ahmed Kadry
- Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, USA; (A.G.); (M.E.); (A.K.); (T.S.M.)
- Department of Dermatology and Venereology, Al-Azhar University, Cairo 11651, Egypt
| | - Thomas S. McCormick
- Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, USA; (A.G.); (M.E.); (A.K.); (T.S.M.)
| | - Mahmoud Ghannoum
- Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, USA; (A.G.); (M.E.); (A.K.); (T.S.M.)
- Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
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15
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Li M, Zhang R, Li J, Li J. The Role of C-Type Lectin Receptor Signaling in the Intestinal Microbiota-Inflammation-Cancer Axis. Front Immunol 2022; 13:894445. [PMID: 35619716 PMCID: PMC9127077 DOI: 10.3389/fimmu.2022.894445] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 04/04/2022] [Indexed: 12/13/2022] Open
Abstract
As a subset of pattern recognition receptors (PRRs), C-type lectin-like receptors (CLRs) are mainly expressed by myeloid cells as both transmembrane and soluble forms. CLRs recognize not only pathogen associated molecular patterns (PAMPs), but also damage-associated molecular patterns (DAMPs) to promote innate immune responses and affect adaptive immune responses. Upon engagement by PAMPs or DAMPs, CLR signaling initiates various biological activities in vivo, such as cytokine secretion and immune cell recruitment. Recently, several CLRs have been implicated as contributory to the pathogenesis of intestinal inflammation, which represents a prominent risk factor for colorectal cancer (CRC). CLRs function as an interface among microbiota, intestinal epithelial barrier and immune system, so we firstly discussed the relationship between dysbiosis caused by microbiota alteration and inflammatory bowel disease (IBD), then focused on the role of CLRs signaling in pathogenesis of IBD (including Mincle, Dectin-3, Dectin-1, DCIR, DC-SIGN, LOX-1 and their downstream CARD9). Given that CLRs mediate intricate inflammatory signals and inflammation plays a significant role in tumorigenesis, we finally highlight the specific effects of CLRs on CRC, especially colitis-associated cancer (CAC), hoping to open new horizons on pathogenesis and therapeutics of IBD and CAC.
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Affiliation(s)
- Muhan Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Gut Microbiota Translational Medicine Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Runfeng Zhang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Gut Microbiota Translational Medicine Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ji Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Gut Microbiota Translational Medicine Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jingnan Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Gut Microbiota Translational Medicine Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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16
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Ali MA, Kamal MM, Rahman MH, Siddiqui MN, Haque MA, Saha KK, Rahman MA. Functional dairy products as a source of bioactive peptides and probiotics: current trends and future prospectives. JOURNAL OF FOOD SCIENCE AND TECHNOLOGY 2022; 59:1263-1279. [PMID: 35250052 PMCID: PMC8882518 DOI: 10.1007/s13197-021-05091-8] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Revised: 02/23/2021] [Accepted: 04/04/2021] [Indexed: 12/31/2022]
Abstract
Milk is an incredibly healthy food world-wide. However, the 'lactase deficient' individuals cannot digest milk's carbohydrate lactose. A large part of the world population is depriving of highly beneficial milk proteins like casein, lactoalbumin, lactoglobulin, etc. due to lactose intolerance. Production of functional foods and bioactive peptides from milk with natural antioxidants and the addition of probiotics could be the best alternative to extend the use of milk functionalities. Among different probiotics, the lactic acid bacteria (LAB) like Lactobacillus delbrueckii sub sp. bulgaricus, Streptococcus thermophilus and some species of Bifidobacteria and their metabolites (paraprobiotics and postbiotics) have been given more preference to add in milk-derived functional foods. These species are generally considered as heat-tolerant, highly proteolytic, and peptidolytic towards milk proteins and they liberate smaller molecules of bioactive peptides during fermentation and other processes that stimulate the enzyme lactase to help people in digestion of milk carbohydrate lactose. Moreover, the incorporation of natural antioxidants in yoghurt and other dairy products prevents the rancidity of milk fat. The level of bioactive peptides produced in milk-derived functional foods can be determined by capillary zone electrophoresis, mass spectrometry, fractionation, and other modern assessment techniques. Commercial production of functional probiotic products with bioactive peptides could significantly contribute to reduce milk spoilage, enhance health benefits as well as the growth of the agro-processing industry.
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Affiliation(s)
- Md. Aslam Ali
- Department of Agro-Processing, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, 1706 Bangladesh
| | - Md. Mostafa Kamal
- Department of Food Processing and Preservation, Hajee Mohammad Danesh Science and Technology University, Dinajpur, 5200 Bangladesh
| | - Md. Hafizur Rahman
- Laboratory of Food Chemistry and Nutrition Science, Institute of Food Science and Technology, Chinese Academy of Agricultural Science, Beijing, China
| | - Md. Nurealam Siddiqui
- Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, 1706 Bangladesh
| | - Md. Azizul Haque
- Faculty of Science and Technology, Free University of Bozen-Bolzano, Piazza Università 1, 39100 Bolzano, Italy
| | - Khokan Kumar Saha
- Department of Agricultural Engineering, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, 1706 Bangladesh
| | - Md. Atikur Rahman
- Department of Food Processing and Preservation, Hajee Mohammad Danesh Science and Technology University, Dinajpur, 5200 Bangladesh
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17
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Xie AX, Iguchi N, Clarkson TC, Malykhina AP. Pharmacogenetic inhibition of lumbosacral sensory neurons alleviates visceral hypersensitivity in a mouse model of chronic pelvic pain. PLoS One 2022; 17:e0262769. [PMID: 35077502 PMCID: PMC8789164 DOI: 10.1371/journal.pone.0262769] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 01/04/2022] [Indexed: 12/12/2022] Open
Abstract
The study investigated the cellular and molecular mechanisms in the peripheral nervous system (PNS) underlying the symptoms of urologic chronic pelvic pain syndrome (UCPPS) in mice. This work also aimed to test the feasibility of reversing peripheral sensitization in vivo in alleviating UCPPS symptoms. Intravesical instillation of vascular endothelial growth factor A (VEGFA) was used to induce UCPPS-like symptoms in mice. Spontaneous voiding spot assays and manual Von Frey tests were used to evaluate the severity of lower urinary tract symptoms (LUTS) and visceral hypersensitivity in VEGFA-instilled mice. Bladder smooth muscle strip contractility recordings (BSMSC) were used to identify the potential changes in myogenic and neurogenic detrusor muscle contractility at the tissue-level. Quantitative real-time PCR (qPCR) and fluorescent immunohistochemistry were performed to compare the expression levels of VEGF receptors and nociceptors in lumbosacral dorsal root ganglia (DRG) between VEGFA-instilled mice and saline-instilled controls. To manipulate primary afferent activity, Gi-coupled Designer Receptors Exclusively Activated by Designer Drugs (Gi-DREADD) were expressed in lumbosacral DRG neurons of TRPV1-Cre-ZGreen mice via targeted adeno-associated viral vector (AAVs) injections. A small molecule agonist of Gi-DREADD, clozapine-N-oxide (CNO), was injected into the peritoneum (i. p.) in awake animals to silence TRPV1 expressing sensory neurons in vivo during physiological and behavioral recordings of bladder function. Intravesical instillation of VEGFA in the urinary bladders increased visceral mechanical sensitivity and enhanced RTX-sensitive detrusor contractility. Sex differences were identified in the baseline detrusor contractility responses and VEGF-induced visceral hypersensitivity. VEGFA instillations in the urinary bladder led to significant increases in the mRNA and protein expression of transient receptor potential cation channel subfamily A member 1 (TRPA1) in lumbosacral DRG, whereas the expression levels of transient receptor potential cation channel subfamily V member 1 (TRPV1) and VEGF receptors (VEGFR1 and VEGFR2) remained unchanged when compared to saline-instilled animals. Importantly, the VEGFA-induced visceral hypersensitivity was reversed by Gi-DREADD-mediated neuronal silencing in lumbosacral sensory neurons. Activation of bladder VEGF signaling causes sensory neural plasticity and visceral hypersensitivity in mice, confirming its role of an UCPPS biomarker as identified by the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research studies. Pharmacogenetic inhibition of lumbosacral sensory neurons in vivo completely reversed VEGFA-induced pelvic hypersensitivity in mice, suggesting the strong therapeutic potential for decreasing primary afferent activity in the treatment of pain severity in UCPPS patients.
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Affiliation(s)
- Alison Xiaoqiao Xie
- Department of Surgery, School of Medicine, Anschutz Medical Campus, University of Colorado, Denver, Colorado, United States of America
| | - Nao Iguchi
- Department of Surgery, School of Medicine, Anschutz Medical Campus, University of Colorado, Denver, Colorado, United States of America
| | - Taylor C. Clarkson
- Department of Surgery, School of Medicine, Anschutz Medical Campus, University of Colorado, Denver, Colorado, United States of America
| | - Anna P. Malykhina
- Department of Surgery, School of Medicine, Anschutz Medical Campus, University of Colorado, Denver, Colorado, United States of America
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18
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Song X, Li F, Zhang M, Xia Y, Ai L, Wang G. Effect of D-Ala-Ended Peptidoglycan Precursors on the Immune Regulation of Lactobacillus plantarum Strains. Front Immunol 2022; 12:825825. [PMID: 35126378 PMCID: PMC8807649 DOI: 10.3389/fimmu.2021.825825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 12/20/2021] [Indexed: 11/21/2022] Open
Abstract
The resistance of Lactobacillus plantarum to vancomycin depends on its peptidoglycan composition. Vancomycin has poor binding affinity with peptidoglycan precursors ending in D-alanyl-D-lactate (D-Ala-D-Lac) but binds strongly to peptidoglycan precursors ending in D-alanyl-D-alanine (D-Ala-D-Ala), resulting in resistance and sensitivity, respectively. The ligase Ddl, which generates D-Ala-D-Lac or D-Ala-D-Ala incorporated into the peptidoglycan precursor chain, is responsible for this specificity. To study the effect of peptidoglycan precursors on immunity, we constructed several strains of L. plantarum expressing the ddl gene of Lactococcus lactis to change their peptidoglycan precursors. The change in the termini of the peptidoglycan precursors was determined by the sensitivity of the strains to vancomycin. The overexpression of ddl increased the susceptibility of the strains to vancomycin. We further explored the regulation of the macrophage inflammatory response pathway by the wild-type and constructed strains, and found that these strains induced the MyD88-dependent TRAF6/MAPK pathway, and the increase in D-Ala L. plantarum peptidoglycan precursors increased the secretion of the inflammatory factors IL-6, IL-1β and TNF-α. These results indicate that D-Ala-ended peptidoglycan precursors play a central role in the variable immunomodulatory ability of L. plantarum.
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19
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Singh RP, Shadan A, Ma Y. Biotechnological Applications of Probiotics: A Multifarious Weapon to Disease and Metabolic Abnormality. Probiotics Antimicrob Proteins 2022; 14:1184-1210. [PMID: 36121610 PMCID: PMC9483357 DOI: 10.1007/s12602-022-09992-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/30/2022] [Indexed: 12/25/2022]
Abstract
Consumption of live microorganisms "Probiotics" for health benefits and well-being is increasing worldwide. Their use as a therapeutic approach to confer health benefits has fascinated humans for centuries; however, its conceptuality gradually evolved with methodological advancement, thereby improving our understanding of probiotics-host interaction. However, the emerging concern regarding safety aspects of live microbial is enhancing the interest in non-viable or microbial cell extracts, as they could reduce the risks of microbial translocation and infection. Due to technical limitations in the production and formulation of traditionally used probiotics, the scientific community has been focusing on discovering new microbes to be used as probiotics. In many scientific studies, probiotics have been shown as potential tools to treat metabolic disorders such as obesity, type-2 diabetes, non-alcoholic fatty liver disease, digestive disorders (e.g., acute and antibiotic-associated diarrhea), and allergic disorders (e.g., eczema) in infants. However, the mechanistic insight of strain-specific probiotic action is still unknown. In the present review, we analyzed the scientific state-of-the-art regarding the mechanisms of probiotic action, its physiological and immuno-modulation on the host, and new direction regarding the development of next-generation probiotics. We discuss the use of recently discovered genetic tools and their applications for engineering the probiotic bacteria for various applications including food, biomedical applications, and other health benefits. Finally, the review addresses the future development of biological techniques in combination with clinical and preclinical studies to explain the molecular mechanism of action, and discover an ideal multifunctional probiotic bacterium.
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Affiliation(s)
- Rajnish Prakash Singh
- Department of Bioengineering and Biotechnology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand India
| | - Afreen Shadan
- Dr. Shyama Prasad Mukherjee University, Ranchi, Jharkhand India
| | - Ying Ma
- College of Resource and Environment, Southwest University, Chongqing, China
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Manzoor S, Wani SM, Mir SA, Rizwan D. Role of probiotics and prebiotics in mitigation of different diseases. Nutrition 2022; 96:111602. [PMID: 35182833 DOI: 10.1016/j.nut.2022.111602] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 11/30/2021] [Accepted: 01/13/2022] [Indexed: 11/15/2022]
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Waziri A, Bharti C, Aslam M, Jamil P, Mirza MA, Javed MN, Pottoo U, Ahmadi A, Alam MS. Probiotics for the Chemoprotective Role against the Toxic Effect of Cancer Chemotherapy. Anticancer Agents Med Chem 2022; 22:654-667. [PMID: 33992067 DOI: 10.2174/1871520621666210514000615] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 11/10/2020] [Accepted: 01/05/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Chemo- and radiation therapy-based clinical management of different types of cancers is associated with toxicity and several side effects. Therefore, there is always an unmet need to explore agents that reduce such risk factors. Among these, natural products have attracted much attention because of their potent antioxidant and antitumor effects. In the past, some breakthrough outcomes established that various bacteria in the human intestinal gut are bearing growth-promoting attributes and suppressing the conversion of pro-carcinogens into carcinogens. Hence probiotics integrated approaches are nowadays being explored as rationalized therapeutics in the clinical management of cancer. METHODS Here, published literature was explored to review chemoprotective roles of probiotics against toxic and side effects of chemotherapeutics. RESULTS Apart from excellent anti-cancer abilities, probiotics alleviate toxicity & side effects of chemotherapeutics, with a high degree of safety and efficiency. CONCLUSION Preclinical and clinical evidence suggests that due to the chemoprotective roles of probiotics against side effects and toxicity of chemotherapeutics, their integration in chemotherapy would be a judicious approach.
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Affiliation(s)
- Aafrin Waziri
- University School of Biotechnology, Guru Gobind Singh Indraprastha University, Delhi, India
| | - Charu Bharti
- School of Medical and Allied Sciences, K.R. Mangalam University, Sohna Road, Gurgaon, Haryana-122103, India
| | - Mohammed Aslam
- Faculty of Pharmacy, AL Hawash Private University, Homs, Syria
| | - Parween Jamil
- Faculty of Dentistry, Jamia Millia Islamia, New Delhi, India
| | - Mohd Aamir Mirza
- Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
| | - Md Noushad Javed
- Department of Pharmacy, SMAS, KR Mangalam University, Gurugram, India
- Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
| | - Uzma Pottoo
- Department of Food Science & Technology, School of Applied Sciences & Technology, University of Kashmir, J.K., India
| | - Amirhossein Ahmadi
- Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Md Sabir Alam
- NIMS Institute of Pharmacy, NIMS University, NH-11C, Delhi - Jaipur Expy, Shobha Nagar, Jaipur, Rajasthan India
- SGT College of Pharmacy, SGT University, Gurgaon-Badli Road Chandu, Budhera, Gurugram, Haryana 122505, India
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Taibbi G, Young M, Vyas RJ, Murray MC, Lim S, Predovic M, Jacobs NM, Askin KN, Mason SS, Zanello SB, Vizzeri G, Theriot CA, Parsons-Wingerter P. Opposite response of blood vessels in the retina to 6° head-down tilt and long-duration microgravity. NPJ Microgravity 2021; 7:38. [PMID: 34650071 PMCID: PMC8516890 DOI: 10.1038/s41526-021-00165-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 08/19/2021] [Indexed: 01/13/2023] Open
Abstract
The Spaceflight Associated Neuro-ocular Syndrome (SANS), associated with the headward fluid shifts incurred in microgravity during long-duration missions, remains a high-priority health and performance risk for human space exploration. To help characterize the pathophysiology of SANS, NASA's VESsel GENeration Analysis (VESGEN) software was used to map and quantify vascular adaptations in the retina before and after 70 days of bed rest at 6-degree Head-Down Tilt (HDT), a well-studied microgravity analog. Results were compared to the retinal vascular response of astronauts following 6-month missions to the International Space Station (ISS). By mixed effects modeling, the trends of vascular response were opposite. Vascular density decreased significantly in the 16 retinas of eight astronauts and in contrast, increased slightly in the ten retinas of five subjects after HDT (although with limited significance). The one astronaut retina diagnosed with SANS displayed the greatest vascular loss. Results suggest that microgravity is a major variable in the retinal mediation of fluid shifts that is not reproduced in this HDT bed rest model.
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Affiliation(s)
- Giovanni Taibbi
- Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch at Galveston, Galveston, TX, USA
| | | | - Ruchi J Vyas
- Mori Associates, Ames Research Center, NASA, Moffett Field, Mountain View, CA, USA
| | - Matthew C Murray
- Blue Marble Space Institute of Science, Space Biology Division, Space Technology Mission Directorate, Ames Research Center, NASA, Moffett Field, Mountain View, CA, USA
| | - Shiyin Lim
- Blue Marble Space Institute of Science, Space Biology Division, Space Technology Mission Directorate, Ames Research Center, NASA, Moffett Field, Mountain View, CA, USA
| | - Marina Predovic
- Blue Marble Space Institute of Science, Space Biology Division, Space Technology Mission Directorate, Ames Research Center, NASA, Moffett Field, Mountain View, CA, USA
| | - Nicole M Jacobs
- Blue Marble Space Institute of Science, Space Biology Division, Space Technology Mission Directorate, Ames Research Center, NASA, Moffett Field, Mountain View, CA, USA
| | - Kayleigh N Askin
- National Space Biomedical Research Institute, Ames Research Center, NASA, Moffett Field, Mountain View, CA, USA
| | | | | | - Gianmarco Vizzeri
- Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch at Galveston, Galveston, TX, USA
| | - Corey A Theriot
- KBR, NASA Johnson Space Center, Houston, TX, USA
- Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX, USA
| | - Patricia Parsons-Wingerter
- Low Gravity Exploration Technology, Research and Engineering Directorate, John Glenn Research Center, NASA, Cleveland, OH, USA.
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Vallianou N, Kounatidis D, Christodoulatos GS, Panagopoulos F, Karampela I, Dalamaga M. Mycobiome and Cancer: What Is the Evidence? Cancers (Basel) 2021; 13:cancers13133149. [PMID: 34202433 PMCID: PMC8269322 DOI: 10.3390/cancers13133149] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 06/21/2021] [Accepted: 06/23/2021] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Although comprising a much smaller proportion of the human microbiome, the fungal community has gained much more attention lately due to its multiple and yet undiscovered interactions with the human bacteriome and the host. Head and neck cancer carcinoma, colorectal carcinoma, and pancreatic ductal adenocarcinoma have been associated with dissimilarities in the composition of the mycobiome between cases with cancer and non-cancer subjects. In particular, an abundance of Malassezia has been associated with the onset and progression of colorectal carcinoma and pancreatic adenocarcinoma, while the genera Schizophyllum, a member of the oral mycobiome, is suggested to exhibit anti-cancer potential. The use of multi-omics will further assist in establishing whether alterations in the human mycobiome are causal or a consequence of specific types of cancers. Abstract Background: To date, most researchhas focused on the bacterial composition of the human microbiota. In this review, we synopsize recent data on the human mycobiome and cancer, highlighting specific cancer types based on current available evidence, presenting interesting perspectives and limitations of studies and laboratory methodologies. Recent findings: Head and neck cancer carcinoma (HNCC), colorectal carcinoma (CRC) and pancreatic ductal adenocarcinoma (PDA) have been associated with dissimilarities in the composition of mycobiota between cancer cases and non-cancer participants. Overall, fungal dysbiosis with decreased fungal richness and diversity was common in cancer patients; however, a specific mycobiotic signature in HNSCC or CRC has not emerged. Different strains of Candida albicans have been identified among cases with HNCC, whilst Lichtheimia corymbifera, a member of the Mucoraceae family, has been shown to predominate among patients with oral tongue cancer. Virulence factors of Candida spp. include the formation of biofilm and filamentation, and the secretion of toxins and metabolites. CRC patients present a dysregulated ratio of Basidiomycota/Ascomycota. Abundance of Malassezia has been linked to the occurrence and progression of CRC and PDA, particularly in animal models of PDA. Interestingly, Schizophyllum, a component of the oral mycobiome, may exhibit anti-cancer potential. Conclusion: The human mycobiome, per se, along with its interactions with the human bacteriome and the host, may be implicated in the promotion and progression of carcinogenesis. Fungi may be used as diagnostic and prognostic/predictive tools or treatment targets for cancer in the coming years. More large-scale, prospective, multicentric and longitudinal studies with an integrative multi-omics methodology are required to examine the precise contribution of the mycobiome in the etiopathogenesis of cancer, and to delineate whether changes that occur in the mycobiome are causal or consequent of cancer.
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Affiliation(s)
- Natalia Vallianou
- First Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou Str., 10676 Athens, Greece; (D.K.); (F.P.)
- Correspondence: (N.V.); (M.D.)
| | - Dimitris Kounatidis
- First Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou Str., 10676 Athens, Greece; (D.K.); (F.P.)
| | - Gerasimos Socrates Christodoulatos
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527 Athens, Greece;
| | - Fotis Panagopoulos
- First Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou Str., 10676 Athens, Greece; (D.K.); (F.P.)
| | - Irene Karampela
- Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini St, Haidari, 12462 Athens, Greece;
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527 Athens, Greece;
- Correspondence: (N.V.); (M.D.)
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Lagatuz M, Vyas RJ, Predovic M, Lim S, Jacobs N, Martinho M, Valizadegan H, Kao D, Oza N, Theriot CA, Zanello SB, Taibbi G, Vizzeri G, Dupont M, Grant MB, Lindner DJ, Reinecker HC, Pinhas A, Chui TY, Rosen RB, Moldovan N, Vickerman MB, Radhakrishnan K, Parsons-Wingerter P. Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis. J Vasc Res 2021; 58:207-230. [PMID: 33839725 PMCID: PMC9903340 DOI: 10.1159/000514211] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 12/23/2020] [Indexed: 11/19/2022] Open
Abstract
The molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA's globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic fibroblast growth factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique "fingerprint" or "biomarker" vascular patterns that integrate dominant signaling with physiological response. In vivo experimental examples described here include vascular response to keratinocyte growth factor, a novel vessel tortuosity factor; angiogenic inhibition in humanized tumor xenografts by the anti-angiogenesis drug leronlimab; intestinal vascular inflammation with probiotic protection by Saccharomyces boulardii, and a workflow programming of vascular architecture for 3D bioprinting of regenerative tissues from 2D images. Microvascular remodeling in the human retina is described for astronaut risks in microgravity, vessel tortuosity in diabetic retinopathy, and venous occlusive disease.
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Affiliation(s)
- Mark Lagatuz
- Redline Performance Solutions, Ames Research Center, National Aeronautics and Space Administration, Moffett Field CA, USA
| | - Ruchi J. Vyas
- Mori Associates, Space Biology Division, Ames Research Center, National Aeronautics and Space Administration, Moffett Field CA, USA
| | - Marina Predovic
- Blue Marble Space Institute of Science, Space Biology Division, Ames Research Center, National Aeronautics and Space Administration, Moffett Field CA, USA
| | - Shiyin Lim
- Blue Marble Space Institute of Science, Space Biology Division, Ames Research Center, National Aeronautics and Space Administration, Moffett Field CA, USA
| | - Nicole Jacobs
- Blue Marble Space Institute of Science, Space Biology Division, Ames Research Center, National Aeronautics and Space Administration, Moffett Field CA, USA
| | - Miguel Martinho
- Universities Space Research Association, Intelligent Systems Division, Exploration Technology Directorate, Ames Research Center, National Aeronautics and Space Administration, Moffett Field CA, USA
| | - Hamed Valizadegan
- Universities Space Research Association, Intelligent Systems Division, Exploration Technology Directorate, Ames Research Center, National Aeronautics and Space Administration, Moffett Field CA, USA
| | - David Kao
- Advanced Supercomputing & Intelligent Systems Divisions, Exploration Technology Directorate, Ames Research Center, National Aeronautics and Space Administration, Moffett Field CA, USA
| | - Nikunj Oza
- Advanced Supercomputing & Intelligent Systems Divisions, Exploration Technology Directorate, Ames Research Center, National Aeronautics and Space Administration, Moffett Field CA, USA
| | - Corey A. Theriot
- Department of Preventive Medicine and Community Health, The University of Texas Medical Branch at Galveston, Galveston, TX, USA
- KBRWyle, Johnson Space Center, National Aeronautics and Space Administration, Houston, TX, USA
| | - Susana B. Zanello
- KBRWyle, Johnson Space Center, National Aeronautics and Space Administration, Houston, TX, USA
| | - Giovanni Taibbi
- Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch at Galveston, Galveston, TX, USA
| | - Gianmarco Vizzeri
- Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch at Galveston, Galveston, TX, USA
| | - Mariana Dupont
- Department of Ophthalmology and Visual Sciences, School of Medicine, University of Alabama, Birmingham AL, USA
| | - Maria B. Grant
- Department of Ophthalmology and Visual Sciences, School of Medicine, University of Alabama, Birmingham AL, USA
| | - Daniel J. Lindner
- Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland OH, USA
| | - Hans-Christian Reinecker
- Departments of Medicine and Immunology, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Alexander Pinhas
- Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York, NY, USA
| | - Toco Y. Chui
- Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York, NY, USA
| | - Richard B. Rosen
- Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York, NY, USA
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Nicanor Moldovan
- Department of Ophthalmology, Indiana University School of Medicine and Indiana University Purdue University at Indianapolis IN, USA
- Richard L. Roudebush VA Medical Center, Veteran’s Administration, Indianapolis IN, USA
| | - Mary B. Vickerman
- Data Systems Branch, John Glenn Research Center, National Aeronautics and Space Administration, Cleveland, OH, USA (retired)
| | - Krishnan Radhakrishnan
- Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration, U.S. Department of Health and Human Services, Rockville, MD, USA
- College of Medicine, University of Kentucky, Lexington, KY, USA
| | - Patricia Parsons-Wingerter
- Space Biology Division, Space Technology Mission Directorate, Ames Research Center, National Aeronautics and Space Administration, Moffett Field, CA, USA
- Low Gravity Exploration Technology, Research and Engineering Directorate, John Glenn Research Center, National Aeronautics and Space Administration, Cleveland, OH, USA
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Recent advances in the application of probiotic yeasts, particularly Saccharomyces, as an adjuvant therapy in the management of cancer with focus on colorectal cancer. Mol Biol Rep 2021; 48:951-960. [PMID: 33389533 PMCID: PMC7778720 DOI: 10.1007/s11033-020-06110-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 12/18/2020] [Indexed: 01/31/2023]
Abstract
Today, the increasing rate of cancer-related mortality, has rendered cancer a major global challenge, and the second leading cause of death worldwide. Conventional approaches in the treatment of cancer mainly include chemotherapy, surgery, immunotherapy, and radiotherapy. However, these approaches still come with certain disadvantages, including drug resistance, and different side effects such as gastrointestinal (GI) irritation (e.g., diarrhea, mucositis). This has encouraged scientists to look for alternative therapeutic methods and adjuvant therapies for a more proper treatment of malignancies. Application of probiotics as an adjuvant therapy in the clinical management of cancer appears to be a promising strategy, with several notable advantages, e.g., increased safety, higher tolerance, and negligible GI side effects. Both in vivo and in vitro analyses have indicated the active role of yeast probiotics in mitigating the rate of cancer cell proliferation, and the induction of apoptosis through regulating the expression of cancer-related genes and cellular pathways. Strain-specific anti-cancer activities of yeast probiotics strongly suggest that their administration along with the current cancer therapies may be an efficient method to reduce the side effects of these approaches. The main purpose of this article is to evaluate the efficacy of yeast probiotics in alleviating the adverse effects associated with cancer therapies.
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Vyas RJ, Young M, Murray MC, Predovic M, Lim S, Jacobs NM, Mason SS, Zanello SB, Taibbi G, Vizzeri G, Parsons-Wingerter P. Decreased Vascular Patterning in the Retinas of Astronaut Crew Members as New Measure of Ocular Damage in Spaceflight-Associated Neuro-ocular Syndrome. Invest Ophthalmol Vis Sci 2020; 61:34. [PMID: 33372980 PMCID: PMC7774106 DOI: 10.1167/iovs.61.14.34] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 11/11/2020] [Indexed: 02/04/2023] Open
Abstract
Purpose Ocular structural and functional changes, collectively termed spaceflight-associated neuro-ocular syndrome (SANS), have been described in astronauts undergoing long-duration missions in the microgravity environment of the International Space Station. We tested the hypothesis that retinal vascular remodeling, particularly by smaller vessels, mediates the chronic headward fluid shifts associated with SANS. Methods As a retrospective study, arterial and venous patterns extracted from 30° infrared Heidelberg Spectralis retinal images of eight crew members acquired before and after six-month missions were analyzed with NASA's recently released VESsel GENeration Analysis (VESGEN) software. Output parameters included the fractal dimension and overall vessel length density that was further classified into large and small vascular branching generations. Vascular results were compared with SANS-associated clinical ocular measures. Results Significant postflight decreases in Df, Lv, and in smaller but not larger vessels were quantified in 11 of 16 retinas for arteries and veins (P value for Df, Lv, and smaller vessels in all 16 retinas were ≤0.033). The greatest vascular decreases occurred in the only retina displaying clinical evidence of SANS by choroidal folds and optic disc edema. In the remaining 15 retinas, decreases in vascular density from Df and Lv ranged from minimal to high by a custom Subclinical Vascular Pathology Index. Conclusions Together with VESGEN, the Subclinical Vascular Pathology Index may represent a new, useful SANS biomarker for advancing the understanding of SANS etiology and developing successful countermeasures for long duration space exploration in microgravity, although further research is required to better characterize retinal microvascular adaptations.
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Affiliation(s)
- Ruchi J. Vyas
- SGT Incorporated, NASA Ames Research Center, Mountain View, California, United States
| | | | - Matthew C. Murray
- Ames Blue Marble Space Institute of Science, NASA Ames Research Center, Mountain View, California, United States
| | - Marina Predovic
- Ames Blue Marble Space Institute of Science, NASA Ames Research Center, Mountain View, California, United States
| | - Shiyin Lim
- Ames Blue Marble Space Institute of Science, NASA Ames Research Center, Mountain View, California, United States
| | - Nicole M. Jacobs
- Ames Blue Marble Space Institute of Science, NASA Ames Research Center, Mountain View, California, United States
| | - Sara S. Mason
- MEI Technologies, NASA Johnson Space Center, Houston, Texas, United States
| | | | - Giovanni Taibbi
- Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
| | - Gianmarco Vizzeri
- Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
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Zommiti M, Feuilloley MGJ, Connil N. Update of Probiotics in Human World: A Nonstop Source of Benefactions till the End of Time. Microorganisms 2020; 8:E1907. [PMID: 33266303 PMCID: PMC7760123 DOI: 10.3390/microorganisms8121907] [Citation(s) in RCA: 97] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 11/23/2020] [Accepted: 11/23/2020] [Indexed: 02/06/2023] Open
Abstract
Lactic acid bacteria (LAB) are known for their biotechnological potential. Moreover, LAB are distinguished by amazing criteria: Adjusting the intestinal environment, inhibiting pathogenic microbes in the gastrointestinal tract, ability to reduce pathogen adhesion activity, improving the balance of the microbiota inside the intestine, capabilities of regulating intestinal mucosal immunity, and maintaining intestinal barrier function. The escalating number of research and studies about beneficial microorganisms and their impact on promoting health has attracted a big interest in the last decades. Since antiquity, various based fermented products of different kinds have been utilized as potential probiotic products. Nevertheless, the current upsurge in consumers' interest in bioalternatives has opened new horizons for the probiotic field in terms of research and development. The present review aims at shedding light on the world of probiotics, a continuous story of astonishing success in various fields, in particular, the biomedical sector and pharmaceutical industry, as well as to display the importance of probiotics and their therapeutic potential in purpose to compete for sturdy pathogens and to struggle against diseases and acute infections. Shadows and future trends of probiotics use are also discussed.
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Affiliation(s)
- Mohamed Zommiti
- Unité de Protéomique Fonctionnelle et Potentiel Nutraceutique de la Biodiversité de Tunisie, Institut Supérieur des Sciences Biologiques Appliquées de Tunis, Université Tunis El-Manar, Tunis 1006, Tunisia
| | - Marc G. J. Feuilloley
- Laboratoire de Microbiologie Signaux et Microenvironnement (LMSM) EA 4312, Université de Rouen Normandie, Normandie Université, F-27000 Evreux, France; (M.G.J.F.); (N.C.)
| | - Nathalie Connil
- Laboratoire de Microbiologie Signaux et Microenvironnement (LMSM) EA 4312, Université de Rouen Normandie, Normandie Université, F-27000 Evreux, France; (M.G.J.F.); (N.C.)
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Abstract
Probiotics and prebiotics are microbiota-management instruments for improving human health once they may be beneficial for maintaining a healthy community of gut microbiota and bowel function. Probiotic’s main target is the gut, via the gastrointestinal tract, although direct application to other body zones such as the vaginal tract, the oral cavity, and skin have been studied. The major source of probiotics is fermented dairy products, however, currently, there is a need for novel and non-dairy probiotics, due to the increasing number of lactose-intolerant persons in the world population, tied with the adverse effect of cholesterol contained in fermented dairy foods as well as the increasing number of strict vegetarians. In this review, we describe gut-derived effects in humans of possible microorganisms isolated from wine, such as Saccharomyces and non-Saccharomyces yeasts and bacteria, and other non-dairy fermented beverages. Those microorganisms can be grown and consumed as recommended probiotics, moreover, wine, and other beverages may also be a source of prebiotics such as polyphenols.
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29
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Wang X, Bove AM, Simone G, Ma B. Molecular Bases of VEGFR-2-Mediated Physiological Function and Pathological Role. Front Cell Dev Biol 2020; 8:599281. [PMID: 33304904 PMCID: PMC7701214 DOI: 10.3389/fcell.2020.599281] [Citation(s) in RCA: 189] [Impact Index Per Article: 37.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 10/21/2020] [Indexed: 12/16/2022] Open
Abstract
The vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) play crucial roles in vasculogenesis and angiogenesis. Angiogenesis is an important mechanism in many physiological and pathological processes, and is involved in endothelial cell proliferation, migration, and survival, then leads to further tubulogenesis, and finally promotes formation of vessels. This series of signaling cascade pathways are precisely mediated by VEGF/VEGFR-2 system. The VEGF binding to the IgD2 and IgD3 of VEGFR-2 induces the dimerization of the receptor, subsequently the activation and trans-autophosphorylation of the tyrosine kinase, and then the initiation of the intracellular signaling cascades. Finally the VEGF-activated VEGFR-2 stimulates and mediates variety of signaling transduction, biological responses, and pathological processes in angiogenesis. Several crucial phosphorylated sites Tyr801, Try951, Try1175, and Try1214 in the VEGFR-2 intracellular domains mediate several key signaling processes including PLCγ-PKC, TSAd-Src-PI3K-Akt, SHB-FAK-paxillin, SHB-PI3K-Akt, and NCK-p38-MAPKAPK2/3 pathways. Based on the molecular structure and signaling pathways of VEGFR-2, the strategy of the VEGFR-2-targeted therapy should be considered to employ in the treatment of the VEGF/VEGFR-2-associated diseases by blocking the VEGF/VEGFR-2 signaling pathway, inhibiting VEGF and VEGFR-2 gene expression, blocking the binding of VEGF and VEGFR-2, and preventing the proliferation, migration, and survival of vascular endothelial cells expressing VEGFR-2.
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Affiliation(s)
- Xinrong Wang
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China
| | | | | | - Binyun Ma
- Department of Medicine/Hematology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States
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30
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Xie YH, Chen YX, Fang JY. Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct Target Ther 2020; 5:22. [PMID: 32296018 PMCID: PMC7082344 DOI: 10.1038/s41392-020-0116-z] [Citation(s) in RCA: 1001] [Impact Index Per Article: 200.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 12/24/2019] [Accepted: 12/31/2019] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in the world and was responsible for nearly 881,000 cancer-related deaths in 2018. Surgery and chemotherapy have long been the first choices for cancer patients. However, the prognosis of CRC has never been satisfying, especially for patients with metastatic lesions. Targeted therapy is a new optional approach that has successfully prolonged overall survival for CRC patients. Following successes with the anti-EGFR (epidermal growth factor receptor) agent cetuximab and the anti-angiogenesis agent bevacizumab, new agents blocking different critical pathways as well as immune checkpoints are emerging at an unprecedented rate. Guidelines worldwide are currently updating the recommended targeted drugs on the basis of the increasing number of high-quality clinical trials. This review provides an overview of existing CRC-targeted agents and their underlying mechanisms, as well as a discussion of their limitations and future trends.
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Affiliation(s)
- Yuan-Hong Xie
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China
| | - Ying-Xuan Chen
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.
| | - Jing-Yuan Fang
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.
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Shamekhi S, Lotfi H, Abdolalizadeh J, Bonabi E, Zarghami N. An overview of yeast probiotics as cancer biotherapeutics: possible clinical application in colorectal cancer. Clin Transl Oncol 2020; 22:1227-1239. [PMID: 31919760 DOI: 10.1007/s12094-019-02270-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2019] [Accepted: 12/08/2019] [Indexed: 02/07/2023]
Abstract
The previous reports have established a strong link between diet, lifestyle, and gut microbiota population with the onset of the colorectal cancer (CRC). Administration of probiotics has become a particular interest in prevention and treatment of CRC. As potential dietary complements, probiotics might be able to lower the risk of CRC and manage the safety of traditional cancer therapies such as surgery, radiation therapy, and chemotherapy. This review investigates the promising effects of probiotics as biotherapeutics, with due attention to possible clinical application of yeast probiotics in prevention and treatment of CRC. In addition, various underlying anti-cancer mechanisms are covered here based on scientific evidence and findings from numerous experimental studies. Application of probiotics as biotherapeutics in CRC, however, needs to be approved by human clinical trials. It is of prime concern, to find potential probiotic strains, effective doses for administrations and regimes, and molecular mechanisms involved in prevention and treatment.
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Affiliation(s)
- S Shamekhi
- Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - H Lotfi
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - J Abdolalizadeh
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - E Bonabi
- Department of Medical Microbiology, Faculty of Medicine, Istanbul Aydin University, Istanbul, Turkey
| | - N Zarghami
- Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. .,Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. .,Department of Clinical Biochemistry and Laboratory Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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32
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Yang K, Dong W. Perspectives on Probiotics and Bronchopulmonary Dysplasia. Front Pediatr 2020; 8:570247. [PMID: 33194897 PMCID: PMC7649774 DOI: 10.3389/fped.2020.570247] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Accepted: 08/13/2020] [Indexed: 02/06/2023] Open
Abstract
Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease of preterm infants, associated with high morbidity and hospitalization expenses. With the revolutionary advances in microbiological analysis technology, increasing evidence indicates that children with BPD are affected by lung microbiota dysbiosis, which may be related to the illness occurrence and progression. However, dysbiosis treatment in BPD patients has not been fully investigated. Probiotics are living microorganisms known to improve human health for their anti-inflammatory and anti-tumor effects, and particularly by balancing gut microbiota composition, which promotes gut-lung axis recovery. The aim of the present review is to examine current evidence of lung microbiota dysbiosis and explore potential applications of probiotics in BPD, which may provide new insights into treatment strategies of this disease.
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Affiliation(s)
- Kun Yang
- Department of Newborn Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Wenbin Dong
- Department of Newborn Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China
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33
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Lam S, Zuo T, Ho M, Chan FKL, Chan PKS, Ng SC. Review article: fungal alterations in inflammatory bowel diseases. Aliment Pharmacol Ther 2019; 50:1159-1171. [PMID: 31648369 DOI: 10.1111/apt.15523] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 05/08/2019] [Accepted: 09/11/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Emerging data suggest that alterations in gut fungi may be associated with the pathogenesis of inflammatory bowel disease (IBD). In healthy individuals, gut commensal fungi act synergistically with other members of the microbiota to maintain homeostasis but their role in IBD is less clear. AIM To review the role of gut fungi and their trans-kingdom interactions with bacteria in IBD METHODS: A literature search was conducted on Ovid and Pubmed to select relevant animal and human studies that have reported fungi and IBD. RESULTS There is an increased total fungal load particularly of Candida and Malassezia species in the faeces and mucosa of Crohn's disease patients, and a lower fungal diversity in the faeces of ulcerative colitis patients. Caspase recruitment domain-containing protein (CARD)-9 polymorphism in Crohn's disease patients favours Malassezia colonisation that worsens gut inflammation. Diet high in carbohydrates increased the total abundance of Candida species, whereas protein-rich diet had the opposite effect. Anti-fungal therapies are mostly used to treat Candida albicans or Histoplasma capsulatum infections in IBD, whereas pilot studies of supplementing fungal probiotics Saccharomycopsis fibuligera, Saccharomyces boulardii and Saccharomyces cerevisiae CNCM I-3856 strain showed therapeutic effects in IBD. CONCLUSIONS Gut fungi are altered in patients with Crohn's disease and ulcerative colitis. Modulation of the fungal microbiota can be considered as a therapeutic approach for IBD. Future research should focus on understanding how the fungal microbiota interacts with other components of the gut microbiota in association with the pathogenesis and development of IBD.
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Affiliation(s)
- Siu Lam
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China.,Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, China
| | - Tao Zuo
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
| | - Martin Ho
- Department of Life Sciences, Imperial College London, London, UK
| | - Francis K L Chan
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
| | - Paul K S Chan
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, China
| | - Siew C Ng
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
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34
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Tooke K, Girard B, Vizzard MA. Functional effects of blocking VEGF/VEGFR2 signaling in the rat urinary bladder in acute and chronic CYP-induced cystitis. Am J Physiol Renal Physiol 2019; 317:F43-F51. [PMID: 30995112 DOI: 10.1152/ajprenal.00083.2019] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
High expression of VEGF is associated with immature angiogenesis within the urinary bladder wall and bladder afferent nerve sensitization, leading to visceral hyperalgesia and pelvic pain. Research suggests a shift in VEGF alternative splice variant (VEGF-Axxxa and VEGF-Axxxb) expression with several pathologies (e.g., neuropathic pain and inflammation) as well as differing effects on pain. Translational studies have also demonstrated increased total VEGF expression in the bladders of women with interstitial cystitis/bladder pain syndrome. In the present study, we quantified VEGF alternative splice variant expression in lower urinary tract tissues under control conditions and with cyclophosphamide (CYP)-induced cystitis. Using conscious cystometry and intravesical instillation of a potent and selective VEGF receptor 2 (VEGFR2) tyrosine kinase inhibitor (Ki-8751, 1 mg/kg) in Wistar rats (male and female) with acute and chronic CYP-induced cystitis and control (no CYP) rats, we further determined the functional effects of VEGFR2 blockade on bladder function. With VEGFR2 blockade, bladder capacity increased (P ≤ 0.01) in male and female control rats as well as in male and female rats with acute (P ≤ 0.05) or chronic (P ≤ 0.01 or P ≤ 0.05, respectively) CYP-induced cystitis. Void volume also increased in female control rats (P ≤ 0.01) and female rats with acute (P ≤ 0.05) or chronic (P ≤ 0.05) CYP-induced cystitis as well as in male control rats (P ≤ 0.05) and male rats with chronic CYP-induced cystitis (P ≤ 0.01). These data suggest that VEGF may be a biomarker for interstitial cystitis/bladder pain syndrome and that targeting VEGF/VEGFR2 signaling may be an effective treatment.
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Affiliation(s)
- Katharine Tooke
- Department of Neurological Sciences, Larner College of Medicine, University of Vermont , Burlington, Vermont
| | - Beatrice Girard
- Department of Neurological Sciences, Larner College of Medicine, University of Vermont , Burlington, Vermont
| | - Margaret A Vizzard
- Department of Neurological Sciences, Larner College of Medicine, University of Vermont , Burlington, Vermont
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35
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The STAT3 inhibitor S3I-201 suppresses fibrogenesis and angiogenesis in liver fibrosis. J Transl Med 2018; 98:1600-1613. [PMID: 30206312 DOI: 10.1038/s41374-018-0127-3] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Revised: 08/03/2018] [Accepted: 08/03/2018] [Indexed: 02/07/2023] Open
Abstract
Liver fibrosis is a common pathological response to chronic hepatic injury. STAT3 is actively involved in the fibrogenesis and angiogenesis seen in liver fibrosis. S3I-201 (NSC 74859) is a chemical inhibitor of STAT3 activity, which blocks the dimerization of STAT3, STAT3-DNA binding and transcription activity. This study evaluated the effects of S3I-201 against liver fibrosis. S3I-201 inhibited the proliferation, migration, and actin filament formation in primary human hepatic stellate cells (HSCs), as well as the expression of α-SMA, collagen I and TIMP1 in both primary HSC and in a CCl4-induced fibrosis mouse model. S3I-201 induced both apoptosis and cell cycle arrest in the HSC cell line (LX-2). S3I-201 inhibited the expression of fibrogenesis factors TGFβ1 and TGFβRII, as well as the downstream phosphorylation of Smad2, Smad3, Akt and ERK induced by TGFβ1. In addition to fibrogenesis, both in vitro and in vivo assays showed that S3I-201 inhibited angiogenesis through expression suppression of VEGF and VEGFR2. Moreover, S3I-201 also had a synergistic effect with sorafenib, an FDA approved liver cancer drug, in the proliferation, apoptosis, angiogenesis and fibrogenesis of HSC. S3I-201 suppressed liver fibrosis through multiple mechanisms, and combined with sorafenib, S3I-201 could be a potentially effective antifibrotic agent.
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36
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Szulińska M, Łoniewski I, Skrypnik K, Sobieska M, Korybalska K, Suliburska J, Bogdański P. Multispecies Probiotic Supplementation Favorably Affects Vascular Function and Reduces Arterial Stiffness in Obese Postmenopausal Women-A 12-Week Placebo-Controlled and Randomized Clinical Study. Nutrients 2018; 10:E1672. [PMID: 30400570 PMCID: PMC6265939 DOI: 10.3390/nu10111672] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 10/19/2018] [Accepted: 10/29/2018] [Indexed: 12/22/2022] Open
Abstract
Obesity in the postmenopausal period is associated with an increased risk of cardiovascular diseases in women. One of the key drivers of cardiovascular risk is endothelial dysfunction; thus, this is also a crucial point for studies on new therapeutic methods of cardioprotective properties. The aim of the current study was to evaluate the effect of two doses of multispecies probiotic Ecologic® Barrier supplement on functional (primary endpoint) and biochemical parameters (secondary endpoint) of endothelial dysfunction in obese postmenopausal women in a 12-week randomized, placebo-controlled clinical trial. A total of 81 obese Caucasian women participated in the trial. The subjects were randomly assigned to three groups that received a placebo, a low dose (LD) (2.5 × 10⁸ colony forming units (CFU) per day), or a high dose (HD) (1 × 1010 CFU per day) of lyophilisate powder containing live multispecies probiotic bacteria. The probiotic supplement was administered each day for 12 weeks in two equal portions. A high dose probiotic supplementation for 12 weeks decreased systolic blood pressure, vascular endothelial growth factor, pulse wave analysis systolic pressure, pulse wave analysis pulse pressure, pulse wave analysis augmentation index, pulse wave velocity, interleukin-6, tumor necrosis factor alpha, and thrombomodulin. Low doses of probiotic supplementation decreased the systolic blood pressure and interleukin-6 levels. The mean changes in the estimated parameters, compared among the three groups, revealed significant differences in the vascular endothelial growth factor, the pulse wave analysis systolic pressure, the pulse wave analysis augmentation index, the pulse wave velocity, the tumor necrosis factor alpha, and thrombomodulin. The post hoc tests showed significant differences for all parameters between HD and the placebo group, and HD and LD (besides pulse wave analysis augmentation index). We show for the first time that supplementation with multispecies probiotic Ecologic® Barrier favorably modifies both functional and biochemical markers of vascular dysfunction in obese postmenopausal women.
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Affiliation(s)
- Monika Szulińska
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, University of Medical Sciences in Poznań, Szamarzewskiego Str. 84, 60-569 Poznań, Poland.
| | - Igor Łoniewski
- Department of Biochemistry and Human Nutrition, Pomeranian Medical University in Szczecin, Broniewskiego 24, 71-460 Szczecin, Poland.
| | - Katarzyna Skrypnik
- Institute of Human Nutrition and Dietetics, Poznan University of Life Sciences, Wojska Polskiego St. 31, 60-624 Poznań, Poland.
| | - Magdalena Sobieska
- Department of Rheumatology and Rehabilitation, Poznan University of Medical Sciences, 28. Czerwca 1956r 135/147, 61-55 Poznań, Poland.
| | - Katarzyna Korybalska
- Department of Pathophysiology, Poznan University of Medical Sciences, Rokietnicka 8, 60-806 Poznan, Poland.
| | - Joanna Suliburska
- Institute of Human Nutrition and Dietetics, Poznan University of Life Sciences, Wojska Polskiego St. 31, 60-624 Poznań, Poland.
| | - Paweł Bogdański
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, University of Medical Sciences in Poznań, Szamarzewskiego Str. 84, 60-569 Poznań, Poland.
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Zhou H, Zhang HJ, Guan L, Zhang YN, Li Y, Sun MJ. Mechanism and therapeutic effects of Saccharomyces boulardii on experimental colitis in mice. Mol Med Rep 2018; 18:5652-5662. [PMID: 30387820 PMCID: PMC6236308 DOI: 10.3892/mmr.2018.9612] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Accepted: 10/10/2018] [Indexed: 12/26/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a type of chronic inflammatory disturbance that affects a number of individuals worldwide; the precise mechanism is unclear and treatment is frequently insufficient to maintain patients in remission. Saccharomyces boulardii is a thermophilic, non‑pathogenic yeast that may be administered for prophylaxis and treatment of a variety of diarrheal diseases. Recent clinical studies have demonstrated that it may have a role in IBD; however, the mechanism of action is unclear. The hypoxia‑inducible factors (HIFs) are ubiquitously expressed regulators of cellular adaptation to hypoxia and are central to the adaptive and inflammatory responses of cells of the intestinal mucosa in patients with IBD. The present study aimed to investigate the effects of S. boulardii on dextran sulfate sodium (DSS)‑induced colitis in mice and the effects of S. boulardii on HIFs. Mice were divided into five groups (n=10 mice/group): i) Control; ii) DSS; iii) S. boulardii (Sb) + DSS; iv) normal saline (NS) + DSS; and v) Sb. For 14 consecutive days, mice from the Sb+DSS and Sb groups were given S. boulardii suspension in saline (150 mg/kg/day; final volume 0.2 ml) by oral gavage. The NS+DSS group received the same volume of NS by gavage. The Control mice received water only. From day 8 to day 14, 3.5% DSS was added to the drinking water of the DSS, Sb+DSS and NS+DSS groups to induce acute colitis. Body weight decreased and disease activity index and histological score increased in mice with DSS‑induced colitis. Oral administration of S. boulardii reduced DSS‑induced weight loss, ameliorated the histological damage and protected the colon barrier in mice with DSS‑induced colitis. The expression of HIF‑1α and HIF‑2α in colon tissues was measured by reverse transcription‑quantitative polymerase chain reaction, immunoblotting and immunohistochemistry. The increase in HIFs in the colon induced by DSS was significantly inhibited by S. boulardii treatment. The expression levels of several epithelial‑mesenchymal transition (EMT) markers and of vascular endothelial growth factor (VEGF) that are regulated by HIFs were measured. S. boulardii reduced EMT and decreased expression of VEGF that was induced by DSS treatment. These results indicated that treatment with S. boulardii ameliorated DSS‑induced colitis, partly through downregulation of HIF‑1α and HIF‑2α.
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Affiliation(s)
- Huan Zhou
- Department of Gastroenterology and Endoscopy, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 11000, P.R. China
| | - Hui-Jing Zhang
- Department of Gastroenterology and Endoscopy, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 11000, P.R. China
| | - Lin Guan
- Department of Gastroenterology and Endoscopy, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 11000, P.R. China
| | - Yi-Ning Zhang
- Department of Gastroenterology and Endoscopy, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 11000, P.R. China
| | - Yue Li
- Department of Gastroenterology and Endoscopy, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 11000, P.R. China
| | - Ming-Jun Sun
- Department of Gastroenterology and Endoscopy, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 11000, P.R. China
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Azad MAK, Sarker M, Wan D. Immunomodulatory Effects of Probiotics on Cytokine Profiles. BIOMED RESEARCH INTERNATIONAL 2018; 2018:8063647. [PMID: 30426014 PMCID: PMC6218795 DOI: 10.1155/2018/8063647] [Citation(s) in RCA: 271] [Impact Index Per Article: 38.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2018] [Accepted: 10/08/2018] [Indexed: 12/15/2022]
Abstract
Probiotics confer immunological protection to the host through the regulation, stimulation, and modulation of immune responses. Researchers have shifted their attention to better understand the immunomodulatory effects of probiotics, which have the potential to prevent or alleviate certain pathologies for which proper medical treatment is as yet unavailable. It has been scientifically established that immune cells (T- and B-cells) mediate adaptive immunity and confer immunological protection by developing pathogen-specific memory. However, this review is intended to present the recent studies on immunomodulatory effects of probiotics. In the early section of this review, concepts of probiotics and common probiotic strains are focused on. On a priority basis, the immune system, along with mucosal immunity in the human body, is discussed in this study. It has been summarized that a number of species of Lactobacillus and Bifidobacterium exert vital roles in innate immunity by increasing the cytotoxicity of natural killer cells and phagocytosis of macrophages and mediate adaptive immunity by interacting with enterocytes and dendritic, Th1, Th2, and Treg cells. Finally, immunomodulatory effects of probiotics on proinflammatory and anti-inflammatory cytokine production in different animal models have been extensively reviewed in this paper. Therefore, isolating new probiotic strains and investigating their immunomodulatory effects on cytokine profiles in humans remain a topical issue.
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Affiliation(s)
- Md. Abul Kalam Azad
- Hunan Province Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agroecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, Hunan 410125, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Manobendro Sarker
- Biomass Energy Engineering Research Centre, School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
- Key Laboratory of Urban Agriculture (South), Ministry of Agriculture, 800 Dongchuan Road, Shanghai 200240, China
- Department of Food Engineering and Technology, State University of Bangladesh, Dhaka 1205, Bangladesh
| | - Dan Wan
- Hunan Province Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agroecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, Hunan 410125, China
- Academician Workstation of Hunan Baodong Farming Co., Ltd., Hunan 422001, China
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Abstract
In the 21st century, urbanization represents a major demographic shift in developed and developing countries. Rapid urbanization in the developing world has been associated with an increasing incidence of several autoimmune diseases, including IBD. Patients with IBD exhibit a decrease in the diversity and richness of the gut microbiota, while urbanization attenuates the gut microbial diversity and might have a role in the pathogenesis of IBD. Environmental exposures during urbanization, including Westernization of diet, increased antibiotic use, pollution, improved hygiene status and early-life microbial exposure, have been shown to affect the gut microbiota. The disparate patterns of the gut microbiota composition in rural and urban areas offer an opportunity to understand the contribution of a 'rural microbiome' in potentially protecting against the development of IBD. This Perspective discusses the effect of urbanization and its surrogates on the gut microbiome (bacteriome, virome, mycobiome and helminths) in both human health and IBD and how such changes might be associated with the development of IBD.
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40
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Sivananthan K, Petersen AM. Review ofSaccharomyces boulardiias a treatment option in IBD. Immunopharmacol Immunotoxicol 2018; 40:465-475. [DOI: 10.1080/08923973.2018.1469143] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- Kavitha Sivananthan
- Department of Gastroenterology, Copenhagen University Hospital, Hvidovre, Denmark
- Department of Microbiology, Copenhagen University Hospital, Hvidovre, Denmark
| | - Andreas Munk Petersen
- Department of Gastroenterology, Copenhagen University Hospital, Hvidovre, Denmark
- Department of Microbiology, Copenhagen University Hospital, Hvidovre, Denmark
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41
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Basson AR, Lam M, Cominelli F. Complementary and Alternative Medicine Strategies for Therapeutic Gut Microbiota Modulation in Inflammatory Bowel Disease and their Next-Generation Approaches. Gastroenterol Clin North Am 2017; 46:689-729. [PMID: 29173517 PMCID: PMC5909826 DOI: 10.1016/j.gtc.2017.08.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The human gut microbiome exerts a major impact on human health and disease, and therapeutic gut microbiota modulation is now a well-advocated strategy in the management of many diseases, including inflammatory bowel disease (IBD). Scientific and clinical evidence in support of complementary and alternative medicine, in targeting intestinal dysbiosis among patients with IBD, or other disorders, has increased dramatically over the past years. Delivery of "artificial" stool replacements for fecal microbiota transplantation (FMT) could provide an effective, safer alternative to that of human donor stool. Nevertheless, optimum timing of FMT administration in IBD remains unexplored, and future investigations are essential.
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Affiliation(s)
- Abigail R Basson
- Digestive Health Research Institute, Case Western Reserve University, Cleveland, OH, USA; Department of Medicine, Case Western Reserve University, Cleveland, OH, USA
| | - Minh Lam
- Digestive Health Research Institute, Case Western Reserve University, Cleveland, OH, USA; Department of Medicine, Case Western Reserve University, Cleveland, OH, USA
| | - Fabio Cominelli
- Digestive Health Research Institute, Case Western Reserve University, Cleveland, OH, USA; Department of Medicine, Case Western Reserve University, Cleveland, OH, USA; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
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Sokol H, Leducq V, Aschard H, Pham HP, Jegou S, Landman C, Cohen D, Liguori G, Bourrier A, Nion-Larmurier I, Cosnes J, Seksik P, Langella P, Skurnik D, Richard ML, Beaugerie L. Fungal microbiota dysbiosis in IBD. Gut 2017; 66:1039-1048. [PMID: 26843508 PMCID: PMC5532459 DOI: 10.1136/gutjnl-2015-310746] [Citation(s) in RCA: 874] [Impact Index Per Article: 109.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Revised: 01/12/2016] [Accepted: 01/14/2016] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD. DESIGN Bacterial and fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects (HS) was determined using 16S and ITS2 sequencing, respectively. The obtained sequences were analysed using the Qiime pipeline to assess composition and diversity. Bacterial and fungal taxa associated with clinical parameters were identified using multivariate association with linear models. Correlation between bacterial and fungal microbiota was investigated using Spearman's test and distance correlation. RESULTS We observed that fungal microbiota is skewed in IBD, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with HS. We also identified disease-specific alterations in diversity, indicating that a Crohn's disease-specific gut environment may favour fungi at the expense of bacteria. The concomitant analysis of bacterial and fungal microbiota showed a dense and homogenous correlation network in HS but a dramatically unbalanced network in IBD, suggesting the existence of disease-specific inter-kingdom alterations. CONCLUSIONS Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis.
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Affiliation(s)
- Harry Sokol
- Sorbonne University—UPMC Univ Paris 06, INSERM ERL 1157, Avenir Team Gut Microbiota and Immunity, UMR 7203, Saint-Antoine Hospital, AP-HP, UPMC Univ Paris 06, Paris, France,Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France,Department of Gastroenterology, Saint Antoine Hospital, Paris, France,Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
| | - Valentin Leducq
- Sorbonne University—UPMC Univ Paris 06, INSERM ERL 1157, Avenir Team Gut Microbiota and Immunity, UMR 7203, Saint-Antoine Hospital, AP-HP, UPMC Univ Paris 06, Paris, France,Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
| | - Hugues Aschard
- Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
| | - Hang-Phuong Pham
- ILTOO Pharma, iPEPS ICM, Hôpital Pitié Salpêtrière, Paris, France
| | - Sarah Jegou
- Sorbonne University—UPMC Univ Paris 06, INSERM ERL 1157, Avenir Team Gut Microbiota and Immunity, UMR 7203, Saint-Antoine Hospital, AP-HP, UPMC Univ Paris 06, Paris, France,Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
| | - Cecilia Landman
- Department of Gastroenterology, Saint Antoine Hospital, Paris, France,Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
| | - David Cohen
- Sorbonne University—UPMC Univ Paris 06, INSERM ERL 1157, Avenir Team Gut Microbiota and Immunity, UMR 7203, Saint-Antoine Hospital, AP-HP, UPMC Univ Paris 06, Paris, France,Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France
| | - Giuseppina Liguori
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Anne Bourrier
- Department of Gastroenterology, Saint Antoine Hospital, Paris, France,Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
| | - Isabelle Nion-Larmurier
- Department of Gastroenterology, Saint Antoine Hospital, Paris, France,Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
| | - Jacques Cosnes
- Department of Gastroenterology, Saint Antoine Hospital, Paris, France,Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
| | - Philippe Seksik
- Department of Gastroenterology, Saint Antoine Hospital, Paris, France,Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
| | - Philippe Langella
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France,Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
| | - David Skurnik
- Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA,Massachusetts Technology and Analytics, Brookline, Massachusetts, USA
| | - Mathias L Richard
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France,Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
| | - Laurent Beaugerie
- Department of Gastroenterology, Saint Antoine Hospital, Paris, France,Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
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Saber A, Alipour B, Faghfoori Z, Yari Khosroushahi A. Cellular and molecular effects of yeast probiotics on cancer. Crit Rev Microbiol 2016; 43:96-115. [PMID: 27561003 DOI: 10.1080/1040841x.2016.1179622] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The cancer is one of the main causes of human deaths worldwide. The exact mechanisms of initiation and progression of malignancies are not clear yet, but there is a common agreement about the role of colonic microbiota in the etiology of different cancers. Probiotics have been examined for their anti-cancer effects, and different mechanisms have been suggested about their antitumor functions. Nonpathogenic yeasts, as members of probiotics family, can be effective on gut microbiota dysbiosis. Generally safe yeasts have shown so many beneficial effects on human health. Probiotic yeasts influence physiology, metabolism, and immune homeostasis in the colon and contribute to cancer treatment due to possessing anti-inflammatory, anti-proliferative and anti-cancer properties. This study reviews some of the health-beneficial effects of probiotic yeasts and their biological substances like folic acid and β-glucan on cancer and focuses on the possible cellular and molecular mechanisms of probiotic yeasts such as influencing pathogenic bacteria, inactivation of carcinogenic compounds, especially those derived from food, improvement of intestinal barrier function, modulation of immune responses, antitoxic function, apoptosis, and anti-proliferative effects.
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Affiliation(s)
- Amir Saber
- a Biotechnology Research Center, Faculty of Nutrition, Tabriz University of Medical Sciences , Tabriz , Iran.,b Student Research Committee, Faculty of Nutrition, Tabriz University of Medical Sciences , Tabriz , Iran.,c Department of Biochemistry and Diet Therapy , Faculty of Nutrition, Tabriz University of Medical Sciences , Tabriz , Iran
| | - Beitollah Alipour
- c Department of Biochemistry and Diet Therapy , Faculty of Nutrition, Tabriz University of Medical Sciences , Tabriz , Iran.,d Nutrition Research Center, Faculty of Nutrition, Tabriz University of Medical Sciences , Tabriz , Iran
| | - Zeinab Faghfoori
- e Faculty of Medicine, Semnan University of Medical Sciences , Semnan , Iran
| | - Ahmad Yari Khosroushahi
- f Drug Applied Research Center, Faculty of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran.,g Department of Pharmacognosy , Faculty of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran
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44
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Angiogenesis in Inflammatory Bowel Disease. Int J Inflam 2015; 2015:970890. [PMID: 26839731 PMCID: PMC4709626 DOI: 10.1155/2015/970890] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Revised: 12/07/2015] [Accepted: 12/08/2015] [Indexed: 12/24/2022] Open
Abstract
Angiogenesis is an important component of pathogenesis of inflammatory bowel disease (IBD). Chronic inflammation and angiogenesis are two closely related processes. Chronic intestinal inflammation is dependent on angiogenesis and this angiogenesis is modulated by immune system in IBD. Angiogenesis is a very complex process which includes multiple cell types, growth factors, cytokines, adhesion molecules, and signal transduction. Lymphangiogenesis is a new research area in the pathogenesis of IBD. While angiogenesis supports inflammation via leukocyte migration, carrying oxygen and nutrients, on the other hand, it has a major role in wound healing. Angiogenic molecules look like perfect targets for the treatment of IBD, but they have risk for serious side effects because of their nature.
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Hoffmann TW, Pham HP, Bridonneau C, Aubry C, Lamas B, Martin-Gallausiaux C, Moroldo M, Rainteau D, Lapaque N, Six A, Richard ML, Fargier E, Le Guern ME, Langella P, Sokol H. Microorganisms linked to inflammatory bowel disease-associated dysbiosis differentially impact host physiology in gnotobiotic mice. ISME JOURNAL 2015. [PMID: 26218241 DOI: 10.1038/ismej.2015.127] [Citation(s) in RCA: 96] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Studying host-microbiota interactions are fundamental to understanding the mechanisms involved in intestinal homeostasis and inflammation. In this work, we analyzed these interactions in mice that were mono-associated with six microorganisms that are representative of inflammatory bowel disease (IBD)-associated dysbiosis: the bacteria Bacteroides thetaiotaomicron, adhesive-invasive Escherichia coli (AIEC), Ruminococcus gnavus and Roseburia intestinalis; a yeast used as a probiotic drug, Saccharomyces boulardii CNCM I-745; and another yeast, Candida albicans. Extensive ex vivo analyses including colon transcriptomics, histology, immune response, bile acid metabolism and short-chain fatty acid production were studied. We showed that B. thetaiotaomicron had the highest impact on the immune system because it was almost able to recapitulate the effects of the entire conventional microbiota and notably induced Treg pathways. Furthermore, these analyses uncovered the effects of E. coli AIEC LF82 on indoleamine 2,3-dioxygenase expression and of S. boulardii CNCM I-745 on angiogenesis. These results were confirmed in vitro in human cell lines. Finally, our results suggested that R. gnavus has major effects on metabolism, and notably on tryptophan metabolism. This work therefore reveals that microorganisms with a potential role in intestinal homeostasis and inflammation have specific impacts on the host, and it suggests several tracks to follow to understand intestinal homeostasis and IBD pathogenesis better, providing new insights to identify novel therapeutic targets.
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Affiliation(s)
- Thomas W Hoffmann
- INRA, UMR1319 MICALIS, Jouy en Josas, France.,AgroParisTech, UMR1319 MICALIS, Jouy en Josas, France
| | - Hang-Phuong Pham
- ILTOO Pharma, Institut du Cerveau et de Moelle Epinière, Hôpital Pitié Salpêtrière, Paris, France
| | - Chantal Bridonneau
- INRA, UMR1319 MICALIS, Jouy en Josas, France.,AgroParisTech, UMR1319 MICALIS, Jouy en Josas, France
| | - Camille Aubry
- INRA, UMR1319 MICALIS, Jouy en Josas, France.,AgroParisTech, UMR1319 MICALIS, Jouy en Josas, France
| | - Bruno Lamas
- ERL INSERM U 1157/UMR7203, Faculté de Médecine Saint-Antoine, Université Pierre et Marie Curie (UPMC), Paris, France
| | | | - Marco Moroldo
- INRA, UMR1313 GABI/CRB GADIE, Jouy en Josas, France.,AgroParisTech, UMR1313 GABI, Jouy en Josas, France
| | - Dominique Rainteau
- ERL INSERM U 1157/UMR7203, Faculté de Médecine Saint-Antoine, Université Pierre et Marie Curie (UPMC), Paris, France
| | - Nicolas Lapaque
- INRA, UMR1319 MICALIS, Jouy en Josas, France.,AgroParisTech, UMR1319 MICALIS, Jouy en Josas, France
| | - Adrien Six
- Sorbonne Universités, UPMC Université Paris 06, INSERM UMR_S 959, CNRS FRE 3632, Immunology, Immunopathology, Immunotherapy (I3), Paris, France
| | - Mathias L Richard
- INRA, UMR1319 MICALIS, Jouy en Josas, France.,AgroParisTech, UMR1319 MICALIS, Jouy en Josas, France
| | - Emilie Fargier
- Biocodex, Centre Recherche et Développement, Compiègne, France
| | | | - Philippe Langella
- INRA, UMR1319 MICALIS, Jouy en Josas, France.,AgroParisTech, UMR1319 MICALIS, Jouy en Josas, France
| | - Harry Sokol
- INRA, UMR1319 MICALIS, Jouy en Josas, France.,AgroParisTech, UMR1319 MICALIS, Jouy en Josas, France.,ERL INSERM U 1157/UMR7203, Faculté de Médecine Saint-Antoine, Université Pierre et Marie Curie (UPMC), Paris, France.,AgroParisTech, UMR1313 GABI, Jouy en Josas, France.,Service de Gastroentérologie et Nutrition, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris et Université Paris 6, Paris, France
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Inhibition of Janus kinase-2 signalling pathway ameliorates portal hypertensive syndrome in partial portal hypertensive and liver cirrhosis rats. Dig Liver Dis 2015; 47:315-23. [PMID: 25637451 DOI: 10.1016/j.dld.2014.12.017] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2014] [Revised: 12/17/2014] [Accepted: 12/31/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS JAK2/STAT3 signalling promotes fibrosis, angiogenesis and inflammation in many diseases; however, the role of this pathway in portal hypertension remains obscure. This study aimed to explore the function of JAK2/STAT3 signalling in portal hypertension and estimate the potential therapeutic effect of treatment with the specific inhibitor AG490. METHODS Rats induced by partial portal vein ligation and common bile duct ligation were treated with AG490 for two weeks. Haemodynamic parameters were assessed. The levels of phospho-STAT3 protein and related cytokines were detected by western blotting of splanchnic organs. Liver, spleen and intestine characterization was performed using histological analyses. Peripheral blood cell counts were also detected. RESULTS High levels of phospho-STAT3 protein were detected in portal hypertensive rats. AG490 effectively inhibited JAK2/STAT3 signalling and its downstream cytokines and provided protective effects by decreasing splanchnic neovascularization and inflammation and by attenuating portal pressure and hyperdynamic splanchnic circulation. In cirrhosis rats, AG490 inhibited intrahepatic fibrosis, angiogenesis and inflammation. AG490 improved the peripheral blood cell counts and the splenomegaly observed in these rats. CONCLUSIONS JAK2/STAT3 signalling is essential in portal hypertension, and targeting JAK2/STAT3 may be a promising therapy to treat this condition.
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Abstract
The prevalence of inflammatory bowel diseases (IBD) has been steadily increasing since 1960. They are widespread throughout Europe, North America, China, and Japan and are emerging as a global disease. The equilibrium among epithelial cells, the immune system, and the related microbiota seems to be paramount in ensuring the absence of these IBD. The role of bacteria in the setting of the gut microbiota has been thoroughly documented, but the role of fungi, which are less abundant, needs to be investigated. Our understanding of the fungal microbiota composition and its impact on IBD has greatly increased in the past 8 years. In this review, we compiled data obtained for the composition of fungal gut microbiota. Special attention was paid to the various effects of this microbial community on the IBD, i.e., the mechanisms and immune pathways involved in these interactions.
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Takata K, Tomita T, Okuno T, Kinoshita M, Koda T, Honorat JA, Takei M, Hagihara K, Sugimoto T, Mochizuki H, Sakoda S, Nakatsuji Y. Dietary Yeasts Reduce Inflammation in Central Nerve System via Microflora. Ann Clin Transl Neurol 2014; 2:56-66. [PMID: 25642435 PMCID: PMC4301675 DOI: 10.1002/acn3.153] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2014] [Revised: 10/28/2014] [Accepted: 11/02/2014] [Indexed: 12/20/2022] Open
Abstract
Objectives The intestinal microflora affects the pathogenesis of several autoimmune diseases by influencing immune system function. Some bacteria, such as lactic acid bacteria, have been reported to have beneficial effects on immune function. However, little is known about the effects of yeasts. Here, we aimed to investigate the effects of various dietary yeasts contained in fermented foods on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), and to elucidate the mechanisms underlying these effects. Methods The effects of eight yeasts selected from 18 types of yeasts contained in fermented foods were examined using an EAE model. Of these, Candida kefyr was investigated by analyzing the intestinal microflora and its effects on intestinal and systemic immune states. Results Administration of C. kefyr ameliorated the severity of EAE. Reduced numbers of Th17 cells, suppressed interleukin (IL)-6 production by intestinal explants, and increased Tregs and CD103-positive regulatory dendritic cells in mesenteric lymph nodes (MLNs) were observed. Analysis of 16s-rDNA from feces of C. kefyr-treated mice demonstrated increased Lactobacillales and decreased Bacteroides compared to control flora. Transfer of intestinal microbiota also resulted in decreased Bacteroides and ameliorated symptoms of EAE. Thus, oral administration of C. kefyr ameliorated EAE by altering the microflora, accompanied by increased Tregs and CD103-positive regulatory dendritic cells in MLNs and decreased Th17 cells in the intestinal lamina propria. Interpretation Oral ingestion of C. kefyr may have beneficial effects on MS by modifying microflora. In addition, our findings also suggested the potential health benefits of dietary yeasts.
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Affiliation(s)
- Kazushiro Takata
- Department of Neurology, Osaka University Graduate School of Medicine D4 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Takayuki Tomita
- Discovery Research Laboratories, Kyorin Pharmaceutical Co., ltd. 2399-1, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi, 329-0114, Japan
| | - Tatsusada Okuno
- Department of Neurology, Osaka University Graduate School of Medicine D4 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Makoto Kinoshita
- Laboratory of Immune Regulation, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine C6 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Toru Koda
- Department of Neurology, Osaka University Graduate School of Medicine D4 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Josephe A Honorat
- Department of Neurology, Osaka University Graduate School of Medicine D4 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Masaya Takei
- Discovery Research Laboratories, Kyorin Pharmaceutical Co., ltd. 2399-1, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi, 329-0114, Japan
| | - Kouichiro Hagihara
- Discovery Research Laboratories, Kyorin Pharmaceutical Co., ltd. 2399-1, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi, 329-0114, Japan
| | - Tomoyuki Sugimoto
- Research Division, Hirosaki University Graduate School of Science and Technology 3-bunkyocho, Hirosaki, Aomori, 036-8560, Japan
| | - Hideki Mochizuki
- Department of Neurology, Osaka University Graduate School of Medicine D4 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Saburo Sakoda
- Department of Neurology, National Hospital Organization Toneyama 5-5-1 Toneyama, Toyonaka, Osaka, 560-8552, Japan
| | - Yuji Nakatsuji
- Department of Neurology, Osaka University Graduate School of Medicine D4 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan
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Plaza-Diaz J, Gomez-Llorente C, Fontana L, Gil A. Modulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver by probiotics. World J Gastroenterol 2014; 20:15632-15649. [PMID: 25400447 PMCID: PMC4229528 DOI: 10.3748/wjg.v20.i42.15632] [Citation(s) in RCA: 132] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 05/04/2014] [Accepted: 06/21/2014] [Indexed: 02/06/2023] Open
Abstract
The potential for the positive manipulation of the gut microbiome through the introduction of beneficial microbes, as also known as probiotics, is currently an active area of investigation. The FAO/WHO define probiotics as live microorganisms that confer a health benefit to the host when administered in adequate amounts. However, dead bacteria and bacterial molecular components may also exhibit probiotic properties. The results of clinical studies have demonstrated the clinical potential of probiotics in many pathologies, such as allergic diseases, diarrhea, inflammatory bowel disease and viral infection. Several mechanisms have been proposed to explain the beneficial effects of probiotics, most of which involve gene expression regulation in specific tissues, particularly the intestine and liver. Therefore, the modulation of gene expression mediated by probiotics is an important issue that warrants further investigation. In the present paper, we performed a systematic review of the probiotic-mediated modulation of gene expression that is associated with the immune system and inflammation. Between January 1990 to February 2014, PubMed was searched for articles that were published in English using the MeSH terms "probiotics" and "gene expression" combined with "intestines", "liver", "enterocytes", "antigen-presenting cells", "dendritic cells", "immune system", and "inflammation". Two hundred and five original articles matching these criteria were initially selected, although only those articles that included specific gene expression results (77) were later considered for this review and separated into three major topics: the regulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver. Particular strains of Bifidobacteria, Lactobacilli, Escherichia coli, Propionibacterium, Bacillus and Saccharomyces influence the gene expression of mucins, Toll-like receptors, caspases, nuclear factor-κB, and interleukins and lead mainly to an anti-inflammatory response in cultured enterocytes. In addition, the interaction of commensal bacteria and probiotics with the surface of antigen-presenting cells in vitro results in the downregulation of pro-inflammatory genes that are linked to inflammatory signaling pathways, whereas other anti-inflammatory genes are upregulated. The effects of probiotics have been extensively investigated in animal models ranging from fish to mice, rats and piglets. These bacteria induce a tolerogenic and hyporesponsive immune response in which many genes that are related to the immune system, in particular those genes expressing anti-inflammatory cytokines, are upregulated. By contrast, information related to gene expression in human intestinal cells mediated by the action of probiotics is scarce. There is a need for further clinical studies that evaluate the mechanism of action of probiotics both in healthy humans and in patients with chronic diseases. These types of clinical studies are necessary for addressing the influence of these microorganisms in gene expression for different pathways, particularly those that are associated with the immune response, and to better understand the role that probiotics might have in the prevention and treatment of disease.
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50
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Abstract
Inflammatory bowel diseases (IBD) are chronic, progressive diseases characterized by aberrant immune responses to environmental and gut microbial triggers in genetically susceptible hosts. Clinical, genetic, and experimental data support the role of gut microbes in causing and sustaining these diseases. Our understanding of IBD has changed dramatically as the result of advances in cultivation-independent approaches and computational platforms for the analysis of large data sets. However, investigations relevant to clinical observations and the natural history of the diseases will be essential for the development of microbial, genetic, and biological metrics that may be used to individualize assessment of risk and improve clinical outcomes in IBD.
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