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1.
Front Cell Infect Microbiol ; 12: 854904, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35521214

RESUMO

In recent years, the role of gastric and duodenal microbiota has acquired increasing importance in the homeostasis of the host, although, to date, most evidence concern the faecal microbiota. Indeed, the gastric, and duodenal microbiota are challenging to study, due to gastric acid, bile, digestive enzymes, and rapid transit time. Specifically, the gastric acid environment may influence their bacterial composition since the acid barrier protects against orally ingested microorganisms and leads to their inactivation before reaching the intestine. The aim of this study was to assess a correlation between intragastric pH and gastric as well as intestinal microbiota of patients with histologic gastric alterations. pH was measured in the gastric juice and the bacterial composition in gastric and duodenal biopsies and faecal samples, was investigated via 16s rRNA gene sequencing. The main result is the direct correlation of duodenal microbiota biodiversity, via alpha diversity measures, with intragastric pH values. In particular, patients with hypochlorhydria showed increased duodenal microbiota biodiversity, higher intragastric pH values being prevalent in patients with chronic atrophic gastritis. Lastly, the latter was also strongly associated to the presence of oral bacteria, like Rothia mucilaginosa, Streptococcus salivarius and Granulicatella adiacens, in the duodenal microbiota. In conclusions, our results suggest a low-acid gastric environment as a contributive factor for duodenal dysbiosis, potentially leading to the development of pathological conditions of the gastrointestinal tract.


Assuntos
Acloridria , Infecções por Helicobacter , Helicobacter pylori , Acloridria/patologia , Disbiose/microbiologia , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , RNA Ribossômico 16S/genética
2.
Front Cell Infect Microbiol ; 12: 780354, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493740

RESUMO

Mucous Membrane Pemphigoid is an orphan multi-system autoimmune scarring disease involving mucosal sites, including the ocular surface (OcMMP) and gut. Loss of tolerance to epithelial basement membrane proteins and generation of autoreactive T cell and/or autoantibodies are central to the disease process. The gut microbiome plays a critical role in the development of the immune system. Alteration in the gut microbiome (gut dysbiosis) affects the generation of autoreactive T cells and B cell autoantibody repertoire in several autoimmune conditions. This study examines the relationship between gut microbiome diversity and ocular inflammation in patients with OcMMP by comparing OcMMP gut microbiome profiles with healthy controls. DNA was extracted from faecal samples (49 OcMMP patients, 40 healthy controls), amplified for the V4 region of the 16S rRNA gene and sequenced using Illumina Miseq platform. Sequencing reads were processed using the bioinformatics pipeline available in the mothur v.1.44.1 software. After adjusting for participant factors in the multivariable model (age, gender, BMI, diet, proton pump inhibitor use), OcMMP cohort was found to be associated with lower number of operational taxonomic units (OTUs) and Shannon Diversity Index when compared to healthy controls. Within the OcMMP cohort, the number of OTUs were found to be significantly correlated with both the bulbar conjunctival inflammation score (p=0.03) and the current use of systemic immunotherapy (p=0.02). The linear discriminant analysis effect size scores indicated that Streptococcus and Lachnoclostridium were enriched in OcMMP patients whilst Oxalobacter, Clostridia uncultured genus-level group (UCG) 014, Christensenellaceae R-7 group and butyrate-producing bacteria such as Ruminococcus, Lachnospiraceae, Coprococcus, Roseburia, Oscillospiraceae UCG 003, 005, NK4A214 group were enriched in healthy controls (Log10 LDA score < 2, FDR-adjusted p <0.05). In conclusion, OcMMP patients have gut dysbiosis correlating with bulbar conjunctival inflammation and the use of systemic immunotherapies. This provides a framework for future longitudinal deep phenotyping studies on the role of the gut microbiome in the pathogenesis of OcMMP.


Assuntos
Disbiose , Penfigoide Bolhoso , Clostridiales/genética , Disbiose/microbiologia , Humanos , Inflamação , Membrana Mucosa , RNA Ribossômico 16S/genética
3.
Front Cell Infect Microbiol ; 12: 841465, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433507

RESUMO

Oral cancer is a globally widespread cancer that features among the three most prevalent cancers in India. The risk of oral cancer is elevated by factors such as tobacco consumption, betel-quid chewing, excessive alcohol consumption, unhygienic oral condition, sustained viral infections, and also due to dysbiosis in microbiome composition of the oral cavity. Here, we performed an oral microbiome study of healthy and oral cancer patients to decipher the microbial dysbiosis due to the consumption of smokeless-tobacco-based products and also revealed the tobacco-associated microbiome. The analysis of 196 oral microbiome samples from three different oral sites of 32 healthy and 34 oral squamous cell carcinoma (OSCC) patients indicated health status, site of sampling, and smokeless tobacco consumption as significant covariates associated with oral microbiome composition. Significant similarity in oral microbiome composition of smokeless-tobacco-consuming healthy samples and OSCC samples inferred the possible role of smokeless tobacco consumption in increasing inflammation-associated species in oral microbiome. Significantly higher abundance of Streptococcus was found to adequately discriminate smokeless-tobacco-non-consuming healthy samples from smokeless-tobacco-consuming healthy samples and contralateral healthy site of OSCC samples from the tumor site of OSCC samples. Comparative analysis of oral microbiome from another OSCC cohort also confirmed Streptococcus as a potential marker for healthy oral microbiome. Gram-negative microbial genera such as Prevotella, Capnocytophaga, and Fusobacterium were found to be differentially abundant in OSCC-associated microbiomes and can be considered as potential microbiome marker genera for oral cancer. Association with lipopolysaccharide (LPS) biosynthesis pathway further confirms the differential abundance of Gram-negative marker genera in OSCC microbiomes.


Assuntos
Carcinoma de Células Escamosas , Microbiota , Neoplasias Bucais , Disbiose/microbiologia , Nível de Saúde , Humanos , Neoplasias Bucais/microbiologia , Uso de Tabaco/efeitos adversos
4.
BMC Womens Health ; 22(1): 113, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413875

RESUMO

BACKGROUND: Female reproductive tract dysbiosis impacts implantation. However, whether gut dysbiosis influences implantation failure and whether it accompanies reproductive tract dysbiosis remains scantly explored. Herein, we examined the gut-vaginal microbiota axis in infertile women. METHODS: We recruited 11 fertile women as the controls, and a cohort of 20 infertile women, 10 of whom had recurrent implantation failure (RIF), and another 10 had unexplained infertility (UE). Using amplicon sequencing, which employs PCR to create sequences of DNA called amplicon, we compared the diversity, structure, and composition of faecal and vaginal bacteria of the controls with that of the infertile cohort. Of note, we could only sequence 8 vaginal samples in each group (n = 24/31). RESULT: Compared with the controls, α-diversity and ß-diversity of the gut bacteria among the infertile groups differed significantly (p < 0.05). Taxa analysis revealed enrichment of Gram-positive bacteria in the RIF group, whereas Gram-negative bacteria were relatively abundant in the UE group. Strikingly, mucus-producing genera declined in the infertile cohort (p < 0.05). Hungatella, associated with trimethylamine N-oxide (TMAO) production, were enriched in the infertile cohort (p < 0.05). Vaginal microbiota was dominated by the genus Lactobacillus, with Lactobacillus iners AB-1 being the most abundant species across the groups. Compared with the infertile cohort, overgrowth of anaerobic bacteria, associated with vaginal dysbiosis, such as Leptotrichia and Snethia, occurred in the controls. CONCLUSION: The gut microbiota had little influence on the vaginal microbiota. Gut dysbiosis and vaginal eubiosis occurred in the infertile women, whereas the opposite trend occurred in the controls.


Assuntos
Infertilidade Feminina , Microbiota , Disbiose/complicações , Disbiose/microbiologia , Feminino , Humanos , RNA Ribossômico 16S/genética , Vagina/microbiologia
5.
Front Immunol ; 13: 737536, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401522

RESUMO

Epidemiological and experimental evidence has implicated a potent link between antibiotic exposure and susceptibility to various diseases. Clinically, antibiotic treatment during platinum chemotherapy is associated with poor prognosis in patients with malignancy. In the present study, mucosal antibiotic exposure was assessed for its impact on renal distress as a sequela of platinum-based chemotherapy. Clinical transcriptome dataset-based evaluations demonstrated that levels of dysbiosis-responsive genes were elevated during renal distress, indicating pathological communications between gut and kidney. Experimentally, mucosal exposure to streptomycin aggravated platinum-induced renal tubular lesions in a mouse model. Moreover, antibiotic-induced dysbiosis increased susceptibility to gut mucosal inflammation, epithelial disruption, and bacterial exposure in response to cisplatin treatment. Further investigation of the luminal microbes indicated that antibiotic-induced dysbiosis promoted the dominance of Bacteroides species. Moreover, the functional assessment of dysbiotic microbiota predicted tryptophan metabolic pathways. In particular, dysbiosis-responsive Bacteroides acidifaciens was associated with the production of the uremic toxin indoxyl sulfate and renal injuries. The results of this study including bacterial community-based evaluations provide new predictive insights into the interorgan communications and interventions against dysbiosis-associated disorders.


Assuntos
Disbiose , Microbioma Gastrointestinal , Animais , Antibacterianos/efeitos adversos , Bactérias/metabolismo , Bacteroides/genética , Disbiose/microbiologia , Humanos , Rim , Camundongos
6.
BMC Ophthalmol ; 22(1): 170, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35421938

RESUMO

BACKGROUND: The microbiome could trigger inflammation leading to epigenetic changes and is involved in the pathophysiology of eye diseases; however, its effect on uveitic glaucoma (UG) has not been fully investigated. This study analysed the differences in eyelid and buccal microbiomes in patients with UG using next-generation sequencing. METHODS: The eyelid and buccal specimens of 34 UG and 25 control patients were collected. The taxonomic composition of the microbiome was obtained via 16S ribosomal DNA sequencing. Diversity and differential gene expression analyses (DEG) determined taxon differences between the microbiomes of UG and control groups. RESULTS: In both the eyelid and buccal microbiomes, alpha-diversity was lower in UG patients than controls, while beta-diversity in patients with UG was higher than in controls. DEG analysis of the eyelid microbiome revealed various taxa differences, including enrichment of Paenibacillus and Dermacoccus (p-value, 1.31e-6 and 1.55e-7, respectively) and depletion of Morganella and Lactococcus (p-value, 6.26e-12 and 2.55e-6, respectively) in patients with UG. In the buccal microbiome, taxa such as Lactococcus was significantly depleted (p-value, 1.31e-17), whereas Faecalibacterium was enriched in patients with UG (p-value, 6.12e-8). CONCLUSIONS: The eyelid and buccal microbiomes in patients with UG differ from controls, which raises concerns surrounding environmental influences on the pathogenesis of UG. The reduced Lactococcus in the eyelid and buccal area suggest that microbiota dysbiosis is associated with UG.


Assuntos
Glaucoma , Microbiota , Disbiose/microbiologia , Pálpebras , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Microbiota/genética , RNA Ribossômico 16S/genética
7.
World J Gastroenterol ; 28(10): 1067-1077, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35431497

RESUMO

BACKGROUND: Gut dysbiosis and small intestinal bacterial overgrowth (SIBO) are commonly observed in patients with cirrhosis. Despite the substantial number of articles describing the relations between disorders of gut microbiota and various manifestations of cirrhosis, dysbiosis and SIBO were always studied separately. AIM: To study the relationship of gut dysbiosis and SIBO in cirrhosis. METHODS: This observational study included 47 in-patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. SIBO was assessed using the lactulose hydrogen breath test. RESULTS: SIBO was found in 24/47 (51.1%) patients. Patients with SIBO had a higher abundance of Firmicutes (P = 0.017) and Fusobacteria (P = 0.011), and a lower abundance of Bacteroidetes (P = 0.013) than patients without SIBO. This increase in the abundance of Firmicutes occurred mainly due to an increase in the abundance of bacteria from the genus Blautia (P = 0.020) of the Lachnospiraceae family (P = 0.047), while the abundance of other major families of this phylum [Ruminococcaceae (P = 0.856), Peptostreptococcaceae (P = 0.066), Clostridiaceae (P = 0.463), Eubacteriaceae (P = 0.463), Lactobacillaceae (P = 0.413), and Veillonellaceae (P = 0.632)] did not differ significantly between the patients with and without SIBO. Reduced level of Bacteroidetes in samples from patients with SIBO was a result of the decrease in bacterial numbers from all the major families of this phylum [Bacteroidaceae (P = 0.014), Porphyromonadaceae (P = 0.002), and Rikenellaceae (P = 0.047)], with the exception of Prevotellaceae (P = 0.941). There were no significant differences in the abundance of taxa that were the main biomarkers of cirrhosis-associated gut dysbiosis [Proteobacteria (P = 0.790), Bacilli (P = 0.573), Enterobacteriaceae (P = 0.632), Streptococcaceae (P = 0.170), Staphylococcaceae (P = 0.450), and Enterococcaceae (P = 0.873)] between patients with and without SIBO. CONCLUSION: Despite the differences observed in the gut microbiome between patients with and without SIBO, gut dysbiosis and SIBO are most likely independent disorders of gut microbiota in cirrhosis.


Assuntos
Microbioma Gastrointestinal , Microbiota , Bactérias/genética , Clostridiales , Disbiose/microbiologia , Firmicutes/genética , Humanos , Cirrose Hepática/diagnóstico , RNA Ribossômico 16S/genética
8.
PLoS One ; 17(4): e0267080, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35439275

RESUMO

The current study compared the gut mycobiomes of diabetic rats generated by a streptozotocin chemical challenge, diabetic rats with retinal changes and normal control rats over a period of 4 months. Sustained increase in blood sugar levels (>150 mg/dL) confirmed the induction of diabetes. Histology and immunohistochemistry were used to identify changes in the retinal tissues in the diabetic rats indicative of the animals progressing into diabetic retinopathy. Gut mycobiomes generated using faecal DNA, indicated dysbiosis at the genus level in both diabetic (DM) and diabetic rats with retinal changes (DRC) when compared with the control rats. In Tables 3-6 the specific genera that were significantly increased/decreased in DM1 and DM2 and in DRC1 and DRC2 respectively compared to the respective controls CT1-CT4 rats are listed. Further, the mycobiomes of the DM and DRC rats separated into distinct clusters following heat-map analysis of the discriminating genera. In addition, ß-diversity analysis separated the mycobiomes of DM and DRC rats from that of the control rats, but the mycobiomes of diabetic rats and diabetic rats with retinal changes showed an overlap. Based on the inferred functions of the discriminating genera in the mycobiomes, we speculated that increase in pathogenic fungi might contribute to the inflammatory status both in diabetic rats and rats showing retinal changes.


Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , Micobioma , Animais , Diabetes Mellitus Experimental/complicações , Disbiose/microbiologia , Fezes/microbiologia , Ratos
9.
Nutrients ; 14(7)2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35405953

RESUMO

Intestinal microorganisms impact health by maintaining gut homeostasis and shaping the host immunity, while gut dysbiosis associates with many conditions, including autism, a complex neurodevelopmental disorder with multifactorial aetiology. In autism, gut dysbiosis correlates with symptom severity and is characterised by a reduced bacterial variability and a diminished beneficial commensal relationship. Microbiota can influence the expression of host microRNAs that, in turn, regulate the growth of intestinal bacteria by means of bidirectional host-gut microbiota cross-talk. We investigated possible interactions among intestinal microbes and between them and host transcriptional modulators in autism. To this purpose, we analysed, by "omics" technologies, faecal microbiome, mycobiome, and small non-coding-RNAs (particularly miRNAs and piRNAs) of children with autism and neurotypical development. Patients displayed gut dysbiosis related to a reduction of healthy gut micro- and mycobiota as well as up-regulated transcriptional modulators. The targets of dysregulated non-coding-RNAs are involved in intestinal permeability, inflammation, and autism. Furthermore, microbial families, underrepresented in patients, participate in the production of human essential metabolites negatively influencing the health condition. Here, we propose a novel approach to analyse faeces as a whole, and for the first time, we detected miRNAs and piRNAs in faecal samples of patients with autism.


Assuntos
Transtorno Autístico , Microbioma Gastrointestinal , MicroRNAs , Microbiota , Transtorno Autístico/genética , Criança , Disbiose/microbiologia , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Humanos , MicroRNAs/genética , RNA Interferente Pequeno , RNA não Traduzido
10.
Int J Mol Sci ; 23(7)2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35409057

RESUMO

The maintenance of the physiological values of blood pressure is closely related to unchangeable factors (genetic predisposition or pathological alterations) but also to modifiable factors (dietary fat and salt, sedentary lifestyle, overweight, inappropriate combinations of drugs, alcohol abuse, smoking and use of psychogenic substances). Hypertension is usually characterized by the presence of a chronic increase in systemic blood pressure above the threshold value and is an important risk factor for cardiovascular disease, including myocardial infarction, stroke, micro- and macro-vascular diseases. Hypertension is closely related to functional changes in the endothelium, such as an altered production of vasoconstrictive and vasodilator substances, which lead to an increase in vascular resistance. These alterations make the endothelial tissue unresponsive to autocrine and paracrine stimuli, initially determining an adaptive response, which over time lead to an increase in risk or disease. The gut microbiota is composed of a highly diverse bacterial population of approximately 1014 bacteria. A balanced intestinal microbiota preserves the digestive and absorbent functions of the intestine, protecting from pathogens and toxic metabolites in the circulation and reducing the onset of various diseases. The gut microbiota has been shown to produce unique metabolites potentially important in the generation of hypertension and endothelial dysfunction. This review highlights the close connection between hypertension, endothelial dysfunction and gut microbiota.


Assuntos
Microbioma Gastrointestinal , Hipertensão , Animais , Bactérias , Pressão Sanguínea , Disbiose/microbiologia , Humanos , Hipertensão/microbiologia , Intestinos/microbiologia , Modelos Animais
11.
Circ Res ; 130(8): 1112-1144, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35420913

RESUMO

The microbiota-gut-brain-axis (MGBA) is a bidirectional communication network between gut microbes and their host. Many environmental and host-related factors affect the gut microbiota. Dysbiosis is defined as compositional and functional alterations of the gut microbiota that contribute to the pathogenesis, progression and treatment responses to disease. Dysbiosis occurs when perturbations of microbiota composition and function exceed the ability of microbiota and its host to restore a symbiotic state. Dysbiosis leads to dysfunctional signaling of the MGBA, which regulates the development and the function of the host's immune, metabolic, and nervous systems. Dysbiosis-induced dysfunction of the MGBA is seen with aging and stroke, and is linked to the development of common stroke risk factors such as obesity, diabetes, and atherosclerosis. Changes in the gut microbiota are also seen in response to stroke, and may impair recovery after injury. This review will begin with an overview of the tools used to study the MGBA with a discussion on limitations and potential experimental confounders. Relevant MGBA components are introduced and summarized for a better understanding of age-related changes in MGBA signaling and its dysfunction after stroke. We will then focus on the relationship between the MGBA and aging, highlighting that all components of the MGBA undergo age-related alterations that can be influenced by or even driven by the gut microbiota. In the final section, the current clinical and preclinical evidence for the role of MGBA signaling in the development of stroke risk factors such as obesity, diabetes, hypertension, and frailty are summarized, as well as microbiota changes with stroke in experimental and clinical populations. We conclude by describing the current understanding of microbiota-based therapies for stroke including the use of pre-/pro-biotics and supplementations with bacterial metabolites. Ongoing progress in this new frontier of biomedical sciences will lead to an improved understanding of the MGBA's impact on human health and disease.


Assuntos
Microbiota , Acidente Vascular Cerebral , Envelhecimento , Encéfalo/metabolismo , Disbiose/complicações , Disbiose/metabolismo , Disbiose/microbiologia , Humanos , Obesidade/complicações , Obesidade/metabolismo , Acidente Vascular Cerebral/metabolismo
12.
Front Public Health ; 10: 862598, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35419331

RESUMO

It is difficult to study the intestinal damage induced by space radiation to astronauts directly, and few prediction models exist. However, we can simulate it in patients with pelvic tumor radiotherapy (RT). Radiation-induced intestinal injury (RIII) is common in cancer patients who receieved pelvic and abdominal RT. We dynamically analyzed gut microbiota and metabolites alterations in 17 cervical and endometrial cancer patients after pelvic RT. In patients who later developed grade 2 RIII, dysbiosis of gut microbiota and metabolites were observed. Univariate analysis showed that Erysipelatoclostridium and ptilosteroid A were related to the occurrence of grade 2 RIII. Notably, a strong positive correlation between gut bacteria Erysipelatoclostridium relative abundance and gut metabolite ptilosteroid A expression was found. Furthermore, combinations of Erysipelatoclostridium and ptilosteroid A could provide good diagnostic markers for grade 2 RIII. In conclusion, gut bacteria Erysipelatoclostridium and its related metabolite ptilosteroid A may collaboratively predict RIII, and could be diagnostic biomarkers for RIII and space radiation injury.


Assuntos
Microbioma Gastrointestinal , Lesões por Radiação , Bactérias , Disbiose/microbiologia , Humanos , Pregnanos
13.
Sci Rep ; 12(1): 5481, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361930

RESUMO

It is unclear whether dysbiosis in hepatitis C virus (HCV) infected patients results from the viral infection per se or develops as a result of hepatic dysfunction. We aimed to characterize compositions in gut microbiome before and shortly after HCV clearance. In this prospective cohort study, adult patients with confirmed HCV viremia were screened before receiving direct antiviral agents. Those with recent exposure to antibiotics or probiotics (within one month), prior abdominal surgery, or any malignancy were ineligible. Stool was collected before antiviral therapy started and at 12 weeks after the treatment completed. From the extracted bacterial DNA, 16 s rRNA gene was amplified and sequenced. Each patient was matched 1:2 in age and sex with uninfected controls. A total of 126 individuals were enrolled into analysis. The gut microbiome was significantly different between HCV-infected patients (n = 42), with or without cirrhosis, and their age-and sex-matched controls (n = 84) from the levels of phylum to amplicon sequence variant (all p values < 0.01 by principal coordinates analysis). All patients achieved viral eradication and exhibited no significant changes in the overall composition of gut microbiome following viral eradication (all p values > 0.5), also without significant difference in alpha diversity (all p values > 0.5). For the purpose of exploration, we also reported bacteria found differently abundant before and after HCV eradication, including Coriobacteriaceae, Peptostreptococcaceae, Staphylococcaceae, Morganellaceae, Pasteurellaceae, Succinivibrionaceae, and Moraxellaceae. Gut microbiota is altered in HCV-infected patients as compared with uninfected controls, but the overall microbial compositions do not significantly change shortly after HCV eradication.


Assuntos
Microbioma Gastrointestinal , Hepatite C , Adulto , Antivirais/uso terapêutico , Disbiose/microbiologia , Microbioma Gastrointestinal/genética , Hepatite C/tratamento farmacológico , Humanos , Estudos Prospectivos
14.
World J Gastroenterol ; 28(12): 1204-1219, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35431513

RESUMO

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder in which recurrent abdominal pain is associated with defecation or a change in bowel habits (constipation, diarrhea, or both), and it is often accompanied by symptoms of abdominal bloating and distension. IBS is an important health care issue because it negatively affects the quality of life of patients and places a considerable financial burden on health care systems. Despite extensive research, the etiology and underlying pathophysiology of IBS remain incompletely understood. Proposed mechanisms involved in its pathogenesis include increased intestinal permeability, changes in the immune system, visceral hypersensitivity, impaired gut motility, and emotional disorders. Recently, accumulating evidence has highlighted the important role of the gut microbiota in the development of IBS. Microbial dysbiosis within the gut is thought to contribute to all aspects of its multifactorial pathogenesis. The last few decades have also seen an increasing interest in the impact of antibiotics on the gut microbiota. Moreover, antibiotics have been suggested to play a role in the development of IBS. Extensive research has established that antibacterial therapy induces remarkable shifts in the bacterial community composition that are quite similar to those observed in IBS. This suggestion is further supported by data from cohort and case-control studies, indicating that antibiotic treatment is associated with an increased risk of IBS. This paper summarizes the main findings on this issue and contributes to a deeper understanding of the link between antibiotic use and the development of IBS.


Assuntos
Antibacterianos , Disbiose , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Antibacterianos/efeitos adversos , Disbiose/etiologia , Disbiose/microbiologia , Disbiose/fisiopatologia , Microbioma Gastrointestinal/fisiologia , Humanos , Síndrome do Intestino Irritável/etiologia , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/fisiopatologia , Qualidade de Vida
15.
Front Cell Infect Microbiol ; 12: 757099, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360108

RESUMO

The microbiota has been observed altered in autoimmune diseases, including idiopathic inflammatory myopathies (IIMs), and associated with different treatments. Low-dose IL-2 treatment emerges as a new option for active IIMs. This study aims to explore the role of low-dose IL-2 in regulating intestinal dysbiosis involved in the IIMs. In this study, 13 patients with active IIMs were enrolled and received 1 ×106 IU of IL-2 subcutaneously every other day for 12 weeks plus standard care. The clinical response and immune response were assessed. Stool samples were obtained to explore the structural and functional alterations of the fecal microbiota targeting the V3-V4 region of the 16S rRNA gene and analyze their associations with clinical and immunological characteristics. Our study demonstrated that diversity of microbiota decreased remarkably in patients with IIMs, compared to healthy controls. The inflammatory-related bacteria, such as Prevotellaceae increased, while some butyrate-producing bacteria, such as Pseudobutyrivibrio, Lachnospiraceae, Roseburia, and Blautia, decreased significantly. The alteration associated with disease activities in patients with IIMs. After low-dose IL-2 treatment, 92.31% (12/13) of patients achieved IMACS DOI at week 12. Proportion of Treg cells significantly increased at week 12 compared with that in baseline (15.9% [7.73, 19.4%] vs. 9.89% [6.02, 11.8%], P = 0.015). Interestingly, certain butyrate-producing bacteria increase significantly after IL-2 treatment, like Lachnospiraceae, Pseudobutyrivibrio, etc., and are associated with a rise in L-Asparagine and L-Leucine. The effects of low-dose IL-2 on gut microbiota were more apparent in NOD mice. Together, the data presented demonstrated that low-dose IL-2 was effective in active IIMs and highlighted the potential for modifying the intestinal microbiomes of dysbiosis to treat IIMs.


Assuntos
Dermatomiosite , Microbioma Gastrointestinal , Microbiota , Animais , Dermatomiosite/tratamento farmacológico , Disbiose/tratamento farmacológico , Disbiose/microbiologia , Microbioma Gastrointestinal/fisiologia , Humanos , Interleucina-2 , Camundongos , Camundongos Endogâmicos NOD , RNA Ribossômico 16S/genética
16.
Front Cell Infect Microbiol ; 12: 774335, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444959

RESUMO

The liver is directly connected to the intestines through the portal vein, which enables the gut microbiota and gut-derived products to influence liver health. There is accumulating evidence of decreased gut flora diversity and alcohol sensitivity in patients with various chronic liver diseases, including non-alcoholic/alcoholic liver disease, chronic hepatitis virus infection, primary sclerosing cholangitis and liver cirrhosis. Increased intestinal mucosal permeability and decline in barrier function were also found in these patients. Followed by bacteria translocation and endotoxin uptake, these will lead to systemic inflammation. Specific microbiota and microbiota-derived metabolites are altered in various chronic liver diseases studies, but the complex interaction between the gut microbiota and liver is missing. This review article discussed the bidirectional relationship between the gut and the liver, and explained the mechanisms of how the gut microbiota ecosystem alteration affects the pathogenesis of chronic liver diseases. We presented gut-microbiota targeted interventions that could be the new promising method to manage chronic liver diseases.


Assuntos
Microbioma Gastrointestinal , Hepatopatias , Microbiota , Probióticos , Disbiose/microbiologia , Disbiose/terapia , Humanos , Intestinos/microbiologia , Fígado/metabolismo , Hepatopatias/microbiologia , Hepatopatias/terapia
17.
PLoS One ; 17(4): e0264556, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35472144

RESUMO

Trillions of microbes such as bacteria, fungi, and viruses exist in the healthy human gut microbiome. Although gut bacterial dysbiosis has been extensively studied in multiple sclerosis (MS), the significance of the fungal microbiome (mycobiome) is an understudied and neglected part of the intestinal microbiome in MS. The aim of this study was to characterize the gut mycobiome of patients with relapsing-remitting multiple sclerosis (RRMS), compare it to healthy controls, and examine its association with changes in the bacterial microbiome. We characterized and compared the mycobiome of 20 RRMS patients and 33 healthy controls (HC) using Internal Transcribed Spacer 2 (ITS2) and compared mycobiome interactions with the bacterial microbiome using 16S rRNA sequencing. Our results demonstrate an altered mycobiome in RRMS patients compared with HC. RRMS patients showed an increased abundance of Basidiomycota and decreased Ascomycota at the phylum level with an increased abundance of Candida and Epicoccum genera along with a decreased abundance of Saccharomyces compared to HC. We also observed an increased ITS2/16S ratio, altered fungal and bacterial associations, and altered fungal functional profiles in MS patients compared to HC. This study demonstrates that RRMS patients had a distinct mycobiome with associated changes in the bacterial microbiome compared to HC. There is an increased fungal to bacterial ratio as well as more diverse fungal-bacterial interactions in RRMS patients compared to HC. Our study is the first step towards future studies in delineating the mechanisms through which the fungal microbiome can influence MS disease.


Assuntos
Ascomicetos , Esclerose Múltipla , Micobioma , Ascomicetos/genética , Bactérias/genética , Disbiose/microbiologia , Fungos/genética , Humanos , Micobioma/genética , RNA Ribossômico 16S/genética
18.
Eur J Clin Microbiol Infect Dis ; 41(5): 691-711, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35353280

RESUMO

Cancer being an increasing burden on human health, the use of anticancer drugs has risen over the last decades. The physiological effects of these drugs are not only perceived by the host's cells but also by the microbial cells it harbors as commensals, notably the gut microbiota. Since the early '50 s, the cytotoxicity of anticancer chemotherapy was evaluated on bacteria revealing some antimicrobial activities that result in an established perturbation of the gut microbiota. This perturbation can affect the host's health through dysbiosis, which can lead to multiple complications, but has also been shown to have a direct effect on the treatment efficiency.We, therefore, conducted a review of literature focusing on this triangular relationship involving the microbial communities from the gut, the host's disease, and the anticancer treatment. We focused specifically on the antimicrobial effects of anticancer chemotherapy, their impact on mutagenesis in bacteria, and the perspectives of using bacteria-based tools to help in the diagnostic and treatment of cancer.


Assuntos
Anti-Infecciosos , Microbioma Gastrointestinal , Microbiota , Neoplasias , Bactérias , Disbiose/microbiologia , Microbioma Gastrointestinal/fisiologia , Humanos , Neoplasias/terapia
19.
Int J Mol Sci ; 23(5)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35269654

RESUMO

A chronic kidney disease (CKD) causes uremic toxin accumulation and gut dysbiosis, which further induces gut leakage and worsening CKD. Lipopolysaccharide (LPS) of Gram-negative bacteria and (1➔3)-ß-D-glucan (BG) of fungi are the two most abundant gut microbial molecules. Due to limited data on the impact of intestinal fungi in CKD mouse models, the influences of gut fungi and Lacticaseibacillus rhamnosus L34 (L34) on CKD were investigated using oral C. albicans-administered 5/6 nephrectomy (5/6Nx) mice. At 16 weeks post-5/6Nx, Candida-5/6Nx mice demonstrated an increase in proteinuria, serum BG, serum cytokines (tumor necrotic factor-α; TNF-α and interleukin-6), alanine transaminase (ALT), and level of fecal dysbiosis (Proteobacteria on fecal microbiome) when compared to non-Candida-5/6Nx. However, serum creatinine, renal fibrosis, or gut barrier defect (FITC-dextran assay and endotoxemia) remained comparable between Candida- versus non-Candida-5/6Nx. The probiotics L34 attenuated several parameters in Candida-5/6Nx mice, including fecal dysbiosis (Proteobacteria and Bacteroides), gut leakage (fluorescein isothiocyanate (FITC)-dextran), gut-derived uremic toxin (trimethylamine-N-oxide; TMAO) and indoxyl sulfate; IS), cytokines, and ALT. In vitro, IS combined with LPS with or without BG enhanced the injury on Caco-2 enterocytes (transepithelial electrical resistance and FITC-dextran permeability) and bone marrow-derived macrophages (supernatant cytokines (TNF-α and interleukin-1 ß; IL-1ß) and inflammatory genes (TNF-α, IL-1ß, aryl hydrocarbon receptor, and nuclear factor-κB)), compared with non-IS activation. These injuries were attenuated by the probiotics condition media. In conclusion, Candida administration worsens kidney damage in 5/6Nx mice through systemic inflammation, partly from gut dysbiosis-induced uremic toxins, which were attenuated by the probiotics. The additive effects on cell injury from uremic toxin (IS) and microbial molecules (LPS and BG) on enterocytes and macrophages might be an important underlying mechanism.


Assuntos
Lactobacillus rhamnosus , Insuficiência Renal Crônica , Uremia , Animais , Células CACO-2 , Candida , Citocinas , Disbiose/microbiologia , Glucanos , Humanos , Lactobacillus rhamnosus/fisiologia , Lipopolissacarídeos/toxicidade , Camundongos , Fator de Necrose Tumoral alfa/efeitos adversos
20.
Microbiol Spectr ; 10(2): e0190421, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35311555

RESUMO

Oral antibiotics remain the therapy of choice for severe bacterial infections; however, antibiotic use disrupts the intestinal microbiota, increasing the risk of colonization by intestinal pathogens. Currently, our understanding of antibiotic-mediated disturbances of the microbiota remains at the level of bacterial families or specific species, and little is known about the effect of antibiotics on potentially beneficial and pathogenic bacteria under the conditions of gut microbiota dysbiosis. Additionally, the question of whether the effects of antibiotics on the gut microbiota are temporary or permanent is controversial. In this study, we used 16S rRNA gene sequencing to evaluate the short- and long-term effects of ampicillin, vancomycin, metronidazole, and neomycin on the murine intestinal microbiota. We found that the changes in the intestinal microbiota reflected the antibiotics' mechanisms of action and that dysbiosis of the intestinal microbiota led to competition between different bacterial communities. In particular, an increase in Enterococcus, which accompanies a decrease in probiotics-related genera such as Lactobacillus, is commonly seen across antibiotic treatments. In addition, we found that these oral antibiotics had long-term negative effects on the intestinal microbiota and promoted the development of antibiotic-resistant bacterial strains. These results indicate that ampicillin, vancomycin, metronidazole, and neomycin have long-term negative effects and can cause irreversible changes in the diversity of the intestinal microbiota, thereby increasing the risk of host disease. IMPORTANCE The intestinal microbiota is a dynamic community of hundreds of millions of microorganisms that play important roles in human health. However, treatment with antibiotics can disrupt the delicate balance of this community, leading to deleterious effects on the host such as inflammation and enhanced susceptibility to infection. To date, most studies of the effects of antibiotic treatment on the microbiota have focused on specific intestinal pathogens and bacterial families. However, few studies have investigated the effects of antibiotic treatment on the relative abundance of probiotic bacteria, pathogenic bacteria, and opportunistic bacterial pathogens in the gut.


Assuntos
Microbioma Gastrointestinal , Ampicilina/farmacologia , Animais , Antibacterianos/uso terapêutico , Bactérias/genética , Disbiose/microbiologia , Humanos , Metronidazol/farmacologia , Camundongos , Neomicina/farmacologia , RNA Ribossômico 16S/genética , Vancomicina/farmacologia
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