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4 pages, 213 KiB

Open AccessEditorial

Special Issue “Gut Microbiota, Inflammatory Bowel Diseases, and Therapeutic Targets”

by Eirini Filidou and George Kolios

Pharmaceuticals 2023, 16(5), 714; https://doi.org/10.3390/ph16050714 - 8 May 2023

Viewed by 1563

Abstract

The gut microbiota and its overall genetic composition, the microbiome, have been the subject of extensive research over the last decade within the fields of genomics, transcriptomics and metabolomics, and their role in various other targeted approaches and advanced technologies has been explored [...] Read more.

The gut microbiota and its overall genetic composition, the microbiome, have been the subject of extensive research over the last decade within the fields of genomics, transcriptomics and metabolomics, and their role in various other targeted approaches and advanced technologies has been explored [...] Full article

(This article belongs to the Special Issue Gut Microbiota, Inflammatory Bowel Diseases, and Therapeutic Targets)

Research

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24 pages, 4406 KiB

Open AccessArticle

The Probiotic Strains Bifidοbacterium lactis, Lactobacillus acidophilus, Lactiplantibacillus plantarum and Saccharomyces boulardii Regulate Wound Healing and Chemokine Responses in Human Intestinal Subepithelial Myofibroblasts

by Gesthimani Tarapatzi, Eirini Filidou, Leonidas Kandilogiannakis, Michail Spathakis, Maria Gaitanidou, Konstantinos Arvanitidis, Ioannis Drygiannakis, Vassilis Valatas, Katerina Kotzampassi, Vangelis G. Manolopoulos, George Kolios and Stergios Vradelis

Pharmaceuticals 2022, 15(10), 1293; https://doi.org/10.3390/ph15101293 - 20 Oct 2022

Cited by 19 | Viewed by 4807

Abstract

Bifidobacterium lactis, Lactobacillus acidophilus, Lactiplantibacillus plantarum and Saccharomyces boulardii are common probiotic supplements. Colonic subepithelial myofibroblasts (cSEMFs) are actively involved in mucosal wound healing and inflammation. cSEMFs, isolated from healthy individuals, were stimulated with 10² or 10⁴ cfu/mL of these [...] Read more.

Bifidobacterium lactis, Lactobacillus acidophilus, Lactiplantibacillus plantarum and Saccharomyces boulardii are common probiotic supplements. Colonic subepithelial myofibroblasts (cSEMFs) are actively involved in mucosal wound healing and inflammation. cSEMFs, isolated from healthy individuals, were stimulated with 10² or 10⁴ cfu/mL of these probiotic strains alone and in combination, and their effect on chemokine and wound healing factor expression was assessed by qRT-PCR, ELISA and Sircol Assay, and on cSEMFs migration, by Wound Healing Assay. These strains remained viable and altered cSEMFs’ inflammatory and wound healing behavior, depending on the strain and concentration. cSEMFs treated with a combination of the four probiotics had a moderate, but statistically significant, increase in the mRNA and/or protein expression of chemokines CXCL1, CXCL2, CXCL4, CXCL8, CXCL10, CCL2 and CCL5, and healing factors, collagen type I and III, fibronectin and tissue factor. In contrast, when each strain was administered alone, different effects were observed, with greater increase or decrease in chemokine and healing factor expression, which was balanced by the mixture. Overall, this study highlights that the use of multiple probiotic strains can potentially alert the gut mucosal immune system and promote wound healing, having a better effect on mucosal immunity than the use of single probiotics. Full article

(This article belongs to the Special Issue Gut Microbiota, Inflammatory Bowel Diseases, and Therapeutic Targets)

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15 pages, 3160 KiB

Open AccessArticle

Characterization of the Mucosally-Adherent Duodenal Microbiome in Children with and without Crohn’s Disease

by Kenneth Schmidt, Janelle Noel-MacDonnell, Carrie Vyhlidal, Daniel P. Heruth, Vivekanand Singh, Atif A. Ahmed, Taina Hudson, Veronica Williams and Valentina Shakhnovich

Pharmaceuticals 2022, 15(7), 850; https://doi.org/10.3390/ph15070850 - 11 Jul 2022

Cited by 4 | Viewed by 2451

Abstract

Manipulation of the microbiome is a rational treatment strategy for inflammatory bowel disease (IBD). Compared to the colon and terminal ileum (TI), understanding of the microbial composition in the duodenum is sparse. This gap in knowledge is especially significant for children with Crohn’s [...] Read more.

Manipulation of the microbiome is a rational treatment strategy for inflammatory bowel disease (IBD). Compared to the colon and terminal ileum (TI), understanding of the microbial composition in the duodenum is sparse. This gap in knowledge is especially significant for children with Crohn’s disease (CD) because the prevalence of duodenal CD is higher in children than in adults. Our aim was to characterize the bacterial composition of the mucosally-adherent duodenal microbiome in children with and without CD as a first step toward development of targeted IBD treatment strategies at this disease location. Fresh-frozen mucosal biopsies were obtained from the duodenum and TI of children with treatment-naïve CD and age- and sex-matched controls. Extracted DNA was analyzed for sequence variation in the 16S ribosomal RNA bacterial gene region V4 (Novogene; Beijing, China). Bacterial relative abundance, alpha and beta composition, and diversity, were compared across duodenal and TI samples from the controls and CD groups with and without chronic active inflammation (118 samples from 73 children total; approx. 50% CD), using UniFrac dissimilarity coefficients (α < 0.05), Linear Discriminant Analysis Effect Size (LEfSe) analysis (LDA score ≥ 2), and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) analysis. The relationships between bacterial abundance, sex, age, concomitant medication use, and villous length were assessed. The microbial composition in the duodenum was significantly different from the TI in the control population(R-value = 0.558, p = 0.001) and in children with active CD (R-value = 0.301, p = 0.001). Significant differences in bacterial abundance were noted between the control and CD duodena (LDA > 4). The duodenum of children without CD was characterized by increased abundance in Pseudomonodales, whereas the actively inflamed duodenum in CD was characterized by increased abundance of Bacteroidales, specifically the family Prevotellaceae. This trend is opposite of previously published observations of microbial composition in the TI, where active inflammation was associated with a relative decrease in the abundance of Bacteroidetes and an increase in Proteobacteria, including Pseudomonadales. No statistically significant correlations were noted between abundance and age, sex, concomitant medication use or villous length, except for Bacteroidetes, which significantly decreased in abundance in the TI with age (p = 0.048). The pediatric duodenal microbiome is distinct from the TI and characterized by an increased abundance of Pseudomonodales and Spirochetes in healthy children, and an increased abundance of Bacteroidales in active CD patients. Full article

(This article belongs to the Special Issue Gut Microbiota, Inflammatory Bowel Diseases, and Therapeutic Targets)

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25 pages, 4268 KiB

Open AccessEditor’s ChoiceArticle

A Novel Combination Therapy Using Rosuvastatin and Lactobacillus Combats Dextran Sodium Sulfate-Induced Colitis in High-Fat Diet-Fed Rats by Targeting the TXNIP/NLRP3 Interaction and Influencing Gut Microbiome Composition

by Sameh Saber, Eslam E. Abd El-Fattah, Galal Yahya, Naglaa A. Gobba, Abdalkareem Omar Maghmomeh, Ahmed E. Khodir, Ahmed A. E. Mourad, Ahmed S. Saad, Hager G. Mohammed, Nehal A. Nouh, Ahmed Shata, Noha A. Amin, Magdy Abou El-Rous, Samuel Girgis, Eman El-Ahwany, Eman M. Khalaf, Attalla F. El-Kott and Ahmed M. El-Baz

Pharmaceuticals 2021, 14(4), 341; https://doi.org/10.3390/ph14040341 - 8 Apr 2021

Cited by 47 | Viewed by 5613

Abstract

Inflammasome targeting and controlling dysbiosis are promising therapeutic approaches to control ulcerative colitis. This report is the first to investigate the mechanisms underlying the coloprotective effects of rosuvastatin and Lactobacillus and their combined therapy on dextran sodium sulfate (DSS)-induced colitis in high-fat diet [...] Read more.

Inflammasome targeting and controlling dysbiosis are promising therapeutic approaches to control ulcerative colitis. This report is the first to investigate the mechanisms underlying the coloprotective effects of rosuvastatin and Lactobacillus and their combined therapy on dextran sodium sulfate (DSS)-induced colitis in high-fat diet (HFD)-fed rats. Our results demonstrate the aggravation of intestinal inflammation as a consequence of an HFD following DSS administration. An association between dyslipidemia, LDL oxidation, CD36 expression, ROS generation, thioredoxin-interacting protein (TXNIP) upregulation, and NLRP3 inflammasome activation was demonstrated by DSS exposure in HFD-fed rats. We demonstrated that rosuvastatin/Lactobacillus significantly suppressed the DSS/HFD-induced increase in colon weight/length ratio, DAI, MDI, and myeloperoxidase, as well as corrected dysbiosis and improved histological characteristics. Additionally, caspase-1 activity and IL-1β-driven pyroptotic activity was significantly reduced. Rosuvastatin/Lactobacillus showed prominent anti-inflammatory effects as revealed by the IL-10/IL-12 ratio and the levels of TNF-α and IL-6. These latter effects may be attributed to the inhibition of phosphorylation-induced activation of NF-κB and a concomitant reduction in the expression of NLRP3, pro-IL-1β, and pro-IL-18. Furthermore, rosuvastatin/Lactobacillus reduced Ox-LDL-induced TXNIP and attenuated the inflammatory response by inhibiting NLRP3 inflammasome assembly. To conclude, rosuvastatin/Lactobacillus offers a safe and effective strategy for the management of ulcerative colitis. Full article

(This article belongs to the Special Issue Gut Microbiota, Inflammatory Bowel Diseases, and Therapeutic Targets)

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16 pages, 1839 KiB

Open AccessArticle

Functional Anatomical Changes in Ulcerative Colitis Patients Determine Their Gut Microbiota Composition and Consequently the Possible Treatment Outcome

by Anita Bálint, Klaudia Farkas, Orsolya Méhi, Bálint Kintses, Bálint Márk Vásárhelyi, Eszter Ari, Csaba Pál, Tamara Madácsy, József Maléth, Kata Judit Szántó, István Nagy, Mariann Rutka, Péter Bacsur, Diána Szűcs, Zoltán Szepes, Ferenc Nagy, Anna Fábián, Renáta Bor, Ágnes Milassin and Tamás Molnár

Pharmaceuticals 2020, 13(11), 346; https://doi.org/10.3390/ph13110346 - 28 Oct 2020

Cited by 15 | Viewed by 3164

Abstract

Gut microbial composition alters in some special situations, such as in ulcerative colits (UC) after total proctocolectomy and ileal pouch-anal anastomosis (IPAA) surgery. The aim of our study was to determine the composition of the intestinal microbiome in UC patients after IPAA surgery, [...] Read more.

Gut microbial composition alters in some special situations, such as in ulcerative colits (UC) after total proctocolectomy and ileal pouch-anal anastomosis (IPAA) surgery. The aim of our study was to determine the composition of the intestinal microbiome in UC patients after IPAA surgery, compared with UC patients, familial adenomatous polyposis (FAP) patients after IPAA surgery and healthy controls. Clinical data of patients, blood and faecal samples were collected. Faecal microbiota structure was determined by sequencing the V4 hypervariable region of the 16S rRNA gene. Overall, 56 patients were enrolled. Compared to the Healthy group, both the Pouch active and UC active groups had higher Enterobacteriaceae, Enterococcaceae and Pasteurellaceae abundance. The Pouch and UC groups showed distinct separation based on their alpha and beta bacterial diversities. The UC group had higher Prevotellaceae, Rikenellaceae, Ruminococcaceae abundance compared to the Pouch active group. Pouch and FAP participants showed similar bacterial community composition. There was no significant difference in the bacterial abundance between the active and inactive subgroups of the Pouch or UC groups. Gut microbiome and anatomical status together construct a functional unit that has influence on diversity, in addition to intestinal inflammation that is a part of the pathomechanism in UC. Full article

(This article belongs to the Special Issue Gut Microbiota, Inflammatory Bowel Diseases, and Therapeutic Targets)

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Review

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14 pages, 350 KiB

Open AccessReview

Metabolomics Insights into Inflammatory Bowel Disease: A Comprehensive Review

by Laila Aldars-García, Javier P. Gisbert and María Chaparro

Pharmaceuticals 2021, 14(11), 1190; https://doi.org/10.3390/ph14111190 - 20 Nov 2021

Cited by 38 | Viewed by 4614

Abstract

Inflammatory bowel disease (IBD) is a chronic, complex relapsing disorder characterised by immune dysregulation, gut microbiota alteration, and disturbed intestinal permeability. The diagnosis and the management of IBD are challenging due to the recurrent nature and complex evolution of the disease. Furthermore, the [...] Read more.

Inflammatory bowel disease (IBD) is a chronic, complex relapsing disorder characterised by immune dysregulation, gut microbiota alteration, and disturbed intestinal permeability. The diagnosis and the management of IBD are challenging due to the recurrent nature and complex evolution of the disease. Furthermore, the molecular mechanism underlying the aetiology and pathogenesis of IBD is still poorly understood. There is an unmet need for novel, reliable, and noninvasive tools for diagnosing and monitoring IBD. In addition, metabolomic profiles may provide a priori determination of optimal therapeutics and reveal novel targets for therapies. This review tries to gather scientific evidence to summarise the emerging contribution of metabolomics to elucidate the mechanisms underlying IBD and changes associated with disease phenotype and therapies, as well as to identify biomarkers with metabolic imbalance in those patients. Metabolite changes during health and disease could provide insights into the disease pathogenesis and the discovery of novel indicators for the diagnosis and prognosis assessment of IBD. Metabolomic studies in IBD have shown changes in tricarboxylic acid cycle intermediates, amino-acid and fatty-acid metabolism, and oxidative pathways. Metabolomics has made progress towards identifying metabolic alterations that may provide clinically useful biomarkers and a deeper understanding of the disease. However, at present, there is insufficient evidence evaluating the predictive accuracy of these molecular signatures and their diagnostic ability, which is necessary before metabolomic data can be translated into clinical practice. Full article

(This article belongs to the Special Issue Gut Microbiota, Inflammatory Bowel Diseases, and Therapeutic Targets)

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21 pages, 741 KiB

Open AccessReview

Metabolic Host–Microbiota Interactions in Autophagy and the Pathogenesis of Inflammatory Bowel Disease (IBD)

by Alexander S. Dowdell and Sean P. Colgan

Pharmaceuticals 2021, 14(8), 708; https://doi.org/10.3390/ph14080708 - 22 Jul 2021

Cited by 23 | Viewed by 6173

Abstract

Inflammatory bowel disease (IBD) is a family of conditions characterized by chronic, relapsing inflammation of the gastrointestinal tract. IBD afflicts over 3 million adults in the United States and shows increasing prevalence in the Westernized world. Current IBD treatments center on modulation of [...] Read more.

Inflammatory bowel disease (IBD) is a family of conditions characterized by chronic, relapsing inflammation of the gastrointestinal tract. IBD afflicts over 3 million adults in the United States and shows increasing prevalence in the Westernized world. Current IBD treatments center on modulation of the damaging inflammatory response and carry risks such as immunosuppression, while the development of more effective treatments is hampered by our poor understanding of the molecular mechanisms of IBD pathogenesis. Previous genome-wide association studies (GWAS) have demonstrated that gene variants linked to the cellular response to microorganisms are most strongly associated with an increased risk of IBD. These studies are supported by mechanistic work demonstrating that IBD-associated polymorphisms compromise the intestine’s anti-microbial defense. In this review, we summarize the current knowledge regarding IBD as a disease of defects in host–microbe interactions and discuss potential avenues for targeting this mechanism for future therapeutic development. Full article

(This article belongs to the Special Issue Gut Microbiota, Inflammatory Bowel Diseases, and Therapeutic Targets)

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18 pages, 4004 KiB

Open AccessFeature PaperReview

Potential Modulatory Microbiome Therapies for Prevention or Treatment of Inflammatory Bowel Diseases

by Daan V. Bunt, Adriaan J. Minnaard and Sahar El Aidy

Pharmaceuticals 2021, 14(6), 506; https://doi.org/10.3390/ph14060506 - 26 May 2021

Cited by 10 | Viewed by 4290

Abstract

A disturbed interaction between the gut microbiota and the mucosal immune system plays a pivotal role in the development of inflammatory bowel disease (IBD). Various compounds that are produced by the gut microbiota, from its metabolism of diverse dietary sources, have been found [...] Read more.

A disturbed interaction between the gut microbiota and the mucosal immune system plays a pivotal role in the development of inflammatory bowel disease (IBD). Various compounds that are produced by the gut microbiota, from its metabolism of diverse dietary sources, have been found to possess anti-inflammatory and anti-oxidative properties in in vitro and in vivo models relevant to IBD. These gut microbiota-derived metabolites may have similar, or more potent gut homeostasis-promoting effects compared to the widely-studied short-chain fatty acids (SCFAs). Available data suggest that mainly members of the Firmicutes are responsible for producing metabolites with the aforementioned effects, a phylum that is generally underrepresented in the microbiota of IBD patients. Further efforts aiming at characterizing such metabolites and examining their properties may help to develop novel modulatory microbiome therapies to treat or prevent IBD. Full article

(This article belongs to the Special Issue Gut Microbiota, Inflammatory Bowel Diseases, and Therapeutic Targets)

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