RESUMO
Background: The relationship between dysbiosis of the gastrointestinal microbiota and gastric cancer (GC) has been extensively studied. However, microbiota alterations in GC patients vary widely across studies, and reproducible diagnostic biomarkers for early GC are still lacking in multiple populations. Thus, this study aimed to characterize the gastrointestinal microbial communities involved in gastric carcinogenesis through a meta-analysis of multiple published and open datasets. Methods: We analyzed 16S rRNA sequencing data from 1,642 gastric biopsy samples and 394 stool samples across 11 independent studies. VSEARCH, QIIME and R packages such as vegan, phyloseq, cooccur, and random forest were used for data processing and analysis. PICRUSt software was employed to predict functions. Results: The α-diversity results indicated significant differences in the intratumoral microbiota of cancer patients compared to non-cancer patients, while no significant differences were observed in the fecal microbiota. Network analysis showed that the positive correlation with GC-enriched bacteria increased, and the positive correlation with GC-depleted bacteria decreased compared to healthy individuals. Functional analyses indicated that pathways related to carbohydrate metabolism were significantly enriched in GC, while biosynthesis of unsaturated fatty acids was diminished. Additionally, we investigated non-Helicobacter pylori (HP) commensals, which are crucial in both HP-negative and HP-positive GC. Random forest models, constructed using specific taxa associated with GC identified from the LEfSe analysis, revealed that the combination of Lactobacillus and Streptococcus included alone could effectively discriminate between GC patients and healthy individuals in fecal samples (area under the curve (AUC) = 0.7949). This finding was also validated in an independent cohort (AUC = 0.7712). Conclusions: This study examined the intratumoral and fecal microbiota of GC patients from a dual microecological perspective and identified Lactobacillus, Streptococcus, Roseburia, Faecalibacterium and Phascolarctobacterium as intratumoral and intestinal-specific co-differential bacteria. Furthermore, it confirmed the validity of the combination of Lactobacillus and Streptococcus as GC-specific microbial markers across multiple populations, which may aid in the early non-invasive diagnosis of GC.
Assuntos
Fezes , Microbioma Gastrointestinal , RNA Ribossômico 16S , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/microbiologia , Fezes/microbiologia , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/genética , Disbiose/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , CarcinogêneseRESUMO
BACKGROUND: Despite achieving endoscopic remission, over 20% of inflammatory bowel disease (IBD) patients experience chronic abdominal pain. Visceral pain and the microbiome exhibit sex-dependent interactions, while visceral pain in IBD shows a sex bias. Our aim was to evaluate whether post-inflammatory microbial perturbations contribute to visceral hypersensitivity in a sex-dependent manner. METHODS: Males, cycling females, ovariectomized, and sham-operated females were given dextran sodium sulfate to induce colitis and allowed to recover. Germ-free recipients received sex-appropriate and cross-sex fecal microbial transplants (FMT) from post-inflammatory donor mice. Visceral sensitivity was assessed by recording visceromotor responses to colorectal distention. The composition of the microbiota was evaluated via 16S rRNA gene V4 amplicon sequencing, while the metabolome was assessed using targeted (short chain fatty acids - SCFA) and semi-targeted mass spectrometry. RESULTS: Post-inflammatory cycling females developed visceral hyperalgesia when compared to males. This effect was reversed by ovariectomy. Both post-inflammatory males and females exhibited increased SCFA-producing species, but only males had elevated fecal SCFA content. FMT from post-inflammatory females transferred visceral hyperalgesia to both males and females, while FMT from post-inflammatory males could only transfer visceral hyperalgesia to males. CONCLUSIONS: Female sex, hormonal status as well as the gut microbiota play a role in pain modulation. Our data highlight the importance of considering biological sex in the evaluation of visceral pain.
Assuntos
Colite , Disbiose , Microbioma Gastrointestinal , Dor Visceral , Masculino , Feminino , Animais , Disbiose/microbiologia , Dor Visceral/microbiologia , Dor Visceral/fisiopatologia , Dor Visceral/metabolismo , Colite/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Microbiota Fecal , Fatores Sexuais , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/metabolismo , RNA Ribossômico 16S/genética , Fezes/microbiologia , Sulfato de Dextrana , Modelos Animais de Doenças , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/análise , Dor Crônica/microbiologia , Dor Crônica/fisiopatologia , Inflamação/microbiologia , Hiperalgesia/microbiologiaRESUMO
Inflammatory bowel diseases (IBDs) are immune chronic diseases characterized by recurrent episodes, resulting in continuous intestinal barrier damage and intestinal microbiota dysbiosis. Safe strategies aimed at stabilizing and reducing IBDs recurrence have been vigorously pursued. Here, we constructed a recurrent intestinal injury Drosophila model and found that vitamin B12 (VB12), an essential co-factor for organism physiological functions, could effectively protect the intestine and reduce dextran sulfate sodium-induced intestinal barrier disruption. VB12 also alleviated microbial dysbiosis in the Drosophila model and inhibited the growth of gram-negative bacteria. We demonstrated that VB12 could mitigate intestinal damage by activating the hypoxia-inducible factor-1 signaling pathway in injured conditions, which was achieved by regulating the intestinal oxidation. In addition, we also validated the protective effect of VB12 in a murine acute colitis model. In summary, we offer new insights and implications for the potential supportive role of VB12 in the management of recurrent IBDs flare-ups.
Assuntos
Sulfato de Dextrana , Modelos Animais de Doenças , Microbioma Gastrointestinal , Fator 1 Induzível por Hipóxia , Mucosa Intestinal , Transdução de Sinais , Vitamina B 12 , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Vitamina B 12/farmacologia , Vitamina B 12/metabolismo , Camundongos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Transdução de Sinais/efeitos dos fármacos , Sulfato de Dextrana/toxicidade , Fator 1 Induzível por Hipóxia/metabolismo , Colite/metabolismo , Colite/induzido quimicamente , Colite/microbiologia , Colite/patologia , Colite/tratamento farmacológico , Disbiose/microbiologia , Disbiose/metabolismo , Camundongos Endogâmicos C57BL , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Drosophila/metabolismoRESUMO
Periodontitis is a common chronic inflammatory disease, affecting approximately 19% of the global adult population. A relationship between periodontal disease and Alzheimer disease has long been recognized, and recent evidence has been uncovered to link these 2 diseases mechanistically. Periodontitis is caused by dysbiosis in the subgingival plaque microbiome, with a pronounced shift in the oral microbiota from one consisting primarily of Gram-positive aerobic bacteria to one predominated by Gram-negative anaerobes, such as Porphyromonas gingivalis. A common phenomenon shared by all bacteria is the release of membrane vesicles to facilitate biomolecule delivery across long distances. In particular, the vesicles released by P gingivalis and other oral pathogens have been found to transport bacterial components across the blood-brain barrier, initiating the physiologic changes involved in Alzheimer disease. In this review, we summarize recent data that support the relationship between vesicles secreted by periodontal pathogens to Alzheimer disease pathology.
Assuntos
Doença de Alzheimer , Periodontite , Porphyromonas gingivalis , Doença de Alzheimer/microbiologia , Doença de Alzheimer/metabolismo , Humanos , Periodontite/microbiologia , Porphyromonas gingivalis/patogenicidade , Disbiose/microbiologia , Infecções Bacterianas/microbiologia , Barreira Hematoencefálica/microbiologia , Animais , MicrobiotaRESUMO
BACKGROUND: Studies have found dysbiosis of the gut microbiota in individuals infected with the hepatitis B virus (HBV). Tenofovir dipivoxil (TDF) is one of the preferred oral antiviral drugs used for the treatment of chronic hepatitis B (CHB), but the extent to which TDF is able to affect the gut microbiota and inflammatory factors of a patient remains largely unexplored. In this study, we collected stool samples from HBV patients prior to medication and from CHB patients treated with TDF. RESULTS: The gut microbiota and inflammatory factors were assessed in 42 healthy subjects (HC group), 109 HBV-infected subjects, including 48 CHB patients who were not medicated with nucleoside analogue drugs (No-NAs group), and 61 CHB patients who were medicated with TDF (TDF group). 16 S rRNA sequencing revealed that TDF treatment caused significant changes in the gut microbiota of HBV-infected individuals; however, the gut microbiota of HBV-infected individuals did not fully recover to a pre-dysbiosis state. The relative abundance of Bacteroidota gradually decreased from the HC group to the No-NAs and TDF groups. The relative abundance of Fusobacteriota was significantly higher in the No-NAs group than in the HC group. At the genus level, Dialister, Eubacterium_hallii_group, Halomonas, Collinsella, Sphingomonas, Xanthomonadaceae_unclassified, and Rhizobiaceae_unclassified were overrepresented; while the abundance of Bacteroides and Fusobacterium decreased significantly in the No-NAs and TDF groups. CONCLUSIONS: This study showed that TDF treatment significantly improved the regulation of the gut microbiota and aided in dysbiosis recovery. We did not observe significant improvement in serum inflammatory factor concentrations, which may be related to the relatively short duration of TDF administration in this study.
Assuntos
Antivirais , Bactérias , Disbiose , Fezes , Microbioma Gastrointestinal , Hepatite B Crônica , Tenofovir , Humanos , Disbiose/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Tenofovir/uso terapêutico , Tenofovir/administração & dosagem , Masculino , Feminino , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Hepatite B Crônica/microbiologia , Adulto , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Fezes/microbiologia , Fezes/virologia , RNA Ribossômico 16S/genética , Vírus da Hepatite B/genética , Vírus da Hepatite B/efeitos dos fármacosRESUMO
Atopic dermatitis (AD) is a common and recurrent skin disease characterized by skin barrier dysfunction, inflammation and chronic pruritus, with wide heterogeneity in terms of age of onset, clinical course and persistence over the lifespan. Although the pathogenesis of the disease are unclear, epidermal barrier dysfunction, immune and microbial dysregulation, and environmental factors are known to be critical etiologies in AD pathology. The skin microbiota represents an ecosystem consisting of numerous microbial species that interact with each other as well as host epithelial cells and immune cells. Although the skin microbiota benefits the host by supporting the basic functions of the skin and preventing the colonization of pathogens, disruption of the microbial balance (dysbiosis) can cause skin diseases such as AD. Although AD is a dermatological disease, recent evidence has shown that changes in microbiota composition in the skin and intestine contribute to the pathogenesis of AD. Environmental factors that contribute to skin barrier dysfunction and microbial dysbiosis in AD include allergens, diet, irritants, air pollution, epigenetics and microbial exposure. Knowing the microbial combination of intestin, as well as the genetic and epigenetic determinants associated with the development of autoantibodies, may help elucidate the pathophysiology of the disease. The skin of patients with AD is characterized by microbial dysbiosis as a result of reduced microbial diversity and overgrowth of the pathogens such as Staphylococcus aureus. Recent studies have revealed the importance of building a strong immune response against microorganisms during childhood and new mechanisms of microbial community dynamics in modulating the skin microbiome. Numerous microorganisms are reported to modulate host response through communication with keratinocytes, specific immune cells and adipocytes to improve skin health and barrier function. This growing insight into bioactive substances in the skin microbiota has led to novel biotherapeutic approaches targeting the skin surface for the treatment of AD. This review will provide an updated overview of the skin microbiota in AD and its complex interaction with immune response mechanisms, as well as explore possible underlying mechanisms in the pathogenesis of AD and provide insights into new therapeutic developments for the treatment of AD. It also focuses on restoring skin microbial homeostasis, aiming to reduce inflammation by repairing the skin barrier.
Assuntos
Dermatite Atópica , Disbiose , Pele , Staphylococcus aureus , Dermatite Atópica/microbiologia , Dermatite Atópica/imunologia , Humanos , Staphylococcus aureus/imunologia , Staphylococcus aureus/fisiologia , Pele/microbiologia , Pele/imunologia , Pele/patologia , Disbiose/microbiologia , Disbiose/imunologia , Microbiota/imunologia , Animais , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologiaRESUMO
Arteriosclerotic cerebral small vessel disease (aCSVD) is a major cause of stroke and dementia. Although its underlying pathogenesis remains poorly understood, both inflammaging and gut microbiota dysbiosis have been hypothesized to play significant roles. This study investigated the role of gut microbiota in the pathogenesis of aCSVD through a comparative analysis of the gut microbiome and metabolome between CSVD patients and healthy controls. The results showed that patients with aCSVD exhibited a marked reduction in potentially beneficial bacterial species, such as Faecalibacterium prausnitzli and Roseburia intestinalis, alongside an increase in taxa from Bacteroides and Proteobacteria. Integrated metagenomic and metabolomic analyses revealed that alterations in microbial metabolic pathways, including LPS biosynthesis and phenylalanine-tyrosine metabolism, were associated with the status of aCSVD. Our findings indicated that microbial LPS biosynthesis and phenylalanine-tyrosine metabolism potentially influenced the symptoms and progression of aCSVD via pro-inflammatory effect and modulation of systemic neurotransmitters, respectively. These results imply that gut microbiota characteristics may serve as indicators for early detection of aCSVD and as potential gut-directed therapeutic intervention target.
Assuntos
Eixo Encéfalo-Intestino , Doenças de Pequenos Vasos Cerebrais , Disbiose , Microbioma Gastrointestinal , Neurotransmissores , Humanos , Doenças de Pequenos Vasos Cerebrais/metabolismo , Doenças de Pequenos Vasos Cerebrais/microbiologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Neurotransmissores/metabolismo , Disbiose/microbiologia , Metabolômica , Bactérias/metabolismo , Bactérias/genética , Metaboloma , MultiômicaRESUMO
Emerging research on the microbiome highlights the significant role of gut health in the development of kidney stones, indicating that an imbalance in gut bacteria or dysbiosis can influence the formation of stones by altering oxalate metabolism and urinary metabolite profiles. In particular, the overabundance of specific bacteria such as Enterococcus and Oxalobacter spp., which are known to affect oxalate absorption, is observed in patients with urolithiasis. This study investigates the effects of gut dysbiosis on urolithiasis through fecal microbiota transplantation (FMT) from patients to rats and its impact on urinary mineral excretion and stone formation. Fecal samples from eight patients with calcium oxalate stones and ten healthy volunteers were collected to assess the gut microbiome. These samples were then transplanted to antibiotic-pretreated Wistar rats for a duration of four weeks. After transplantation, we evaluated changes in the fecal gut microbiome profile, urinary mineral excretion rates, and expression levels of intestinal zonula occluden-1 (ZO-1), SLC26A6 and renal NF-κB. In humans, patients with urolithiasis exhibited increased urinary calcium and oxalate levels, along with decreased citrate excretion and increased urinary supersaturation index. The fecal microbiota showed a notable abundance of Bacteroidota. In rodents, urolithiasis-FMT rats showed urinary disturbances similar to patients, including elevated pH, oxalate level, and supersaturation index, despite negative renal pathology. In addition, a slight elevation in the expression of renal NF-κB, a significant intestinal SLC26A6, and a reduction in ZO-1 expression were observed. The gut microbiome of urolithiasis-FMT rats showed an increased abundance of Bacteroidota, particularly Muribaculaceae, compared to their healthy FMT counterparts. In conclusion, the consistent overabundance of Bacteroidota in both urolithiasis patients and urolithiasis-FMT rats is related to altered intestinal barrier function, hyperoxaluria, and renal inflammation. These findings suggest that gut dysbiosis, characterized by an overgrowth of Bacteroidota, plays a crucial role in the pathogenesis of calcium oxalate urolithiasis, underscoring the potential of targeting the gut microbiota as a therapeutic strategy.
Assuntos
Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Cálculos Renais , Ratos Wistar , Animais , Cálculos Renais/microbiologia , Cálculos Renais/metabolismo , Cálculos Renais/terapia , Humanos , Ratos , Masculino , Disbiose/microbiologia , Modelos Animais de Doenças , Fezes/microbiologia , Feminino , Adulto , Pessoa de Meia-IdadeRESUMO
Pathogenic changes in gut microbial composition precede the onset of HIV-1 infection in men who have sex with men (MSM). This process is associated with increased levels of systemic inflammatory biomarkers and risk for AIDS development. Using mediation analysis framework, in this report we link the effects of unprotected receptive intercourse among MSM prior to primary HIV-1 infection to higher levels of proinflammatory cytokines sCD14 and sCD163 in plasma and a significant decrease in the abundance of A. muciniphila, B. caccae, B. fragilis, B. uniformis, Bacteroides spp., Butyricimonas spp., and Odoribacter spp., and a potential increase in the abundance of Dehalobacterium spp. and Methanobrevibacter spp. in stools of MSM with the highest number of sexual partners. These differences in microbiota, together with a reduction in the pairwise correlations among commensal and short-chain fatty acid-producing bacteria with a number of sexual partners, support an increase in gut dysbiosis with the number of sexual partners. These results demonstrate the interconnectedness of sexual behavior, immune response, and microbiota composition, notably among MSM participating in high-risk sexual behaviors.
Assuntos
Microbioma Gastrointestinal , Infecções por HIV , HIV-1 , Homossexualidade Masculina , Inflamação , Comportamento Sexual , Masculino , Humanos , Infecções por HIV/microbiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Adulto , Inflamação/microbiologia , HIV-1/fisiologia , Disbiose/microbiologia , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Anorexia nervosa has the highest mortality rate among psychiatric illnesses. Current treatments remain ineffective for a large fraction of patients. This may be due to unclear mechanisms behind its development and maintenance. Studies exploring the role of the gut microbiome have revealed inconsistent evidence of dysbiosis. This article aims to investigate changes in the gut microbiome, particularly, mean differences in the Firmicutes to Bacteroidetes ratio, in adolescent and adult individuals with anorexia nervosa following inpatient treatment. METHODS: Longitudinal studies investigating gut microbiome composition in inpatient populations of anorexia nervosa before and after treatment were systematically reviewed. Additionally, gut microbiome compositions were characterized in three acute anorexia nervosa inpatients early after admission and after 4-12 weeks of treatment. RESULTS: Review results indicated an increase in the Firmicutes to Bacteroidetes ratio in individuals with anorexia nervosa after treatment. These however did not match values of their healthy counterparts. In the case-series samples, the reverse occurred with samples taken 4 weeks after treatment. In the patient who provided an extra sample 12 weeks after treatment, similar results to the studies included in the review were observed. Furthermore, Firmicutes to Bacteroidetes ratio values in the case-series samples were notably higher in the two patients who had chronic anorexia nervosa. DISCUSSION: Differences in methodologies, small sample sizes, and insufficient data limited the generalizability of the outcomes of the reviewed studies. Results suggest a potentially unique microbiome signature in individuals with chronic anorexia nervosa, which may explain different outcomes in this group of patients.
Assuntos
Anorexia Nervosa , Bacteroidetes , Firmicutes , Microbioma Gastrointestinal , Pacientes Internados , Anorexia Nervosa/microbiologia , Anorexia Nervosa/terapia , Humanos , Microbioma Gastrointestinal/fisiologia , Bacteroidetes/isolamento & purificação , Firmicutes/isolamento & purificação , Feminino , Adulto , Adolescente , Adulto Jovem , Disbiose/microbiologiaRESUMO
The gut microbiota and inflammatory proteins may affect the development of peptic ulcer disease. However, this association remains unclear. We analyzed genome-wide association study data of gut microbiota, inflammatory proteins, and peptic ulcer disease using Mendelian randomization with instrumental variables to assess causal relationships. Various statistical methods, including inverse variance weighting, Mendelian randomization Egger regression, and sensitivity analysis were employed to evaluate the data and calculate mediation ratios. Our findings reveal that the genus Butyriciccus plays a role in mitigating the adverse effects of gastric ulcers by 7.9%, primarily through reducing beta-negative growth factor levels. Additionally, the genus Lachnospiraceae UCG004 can significantly alleviate the negative outcomes of gastric ulcers and reduces hepatocyte growth factor and beta-reserve growth factor levels by 6.39% and 7.45%, respectively. This study highlights the independent and mediating effects of the gut microbiota and inflammatory proteins on peptic ulcers, offering insights on potential pathways and targets for future preventive interventions.
Assuntos
Disbiose , Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Úlcera Péptica , Humanos , Úlcera Péptica/microbiologia , Disbiose/microbiologiaRESUMO
Bacterial extracellular vesicles (BEVs) are nano-sized lipid-shielded structures released by bacteria and that play an important role in intercellular communication. Their broad taxonomic origins and varying cargo compositions suggest their active participation in significant biological mechanisms. Specifically, they are involved in directly modulating microbial ecosystems, competing with other organisms, contributing to pathogenicity, and influencing the immunity of their hosts. This review examines the mechanisms that underlie the modulatory effects of BEVs on gut dynamics and immunity. Understanding how BEVs modulate microbiota composition and functional imbalances is crucial, as gut dysbiosis is implicated not only in the pathogenesis of various gastrointestinal, metabolic, and neurological diseases, but also in reducing resistance to colonization by enteric pathogens, which is particularly concerning given the current antimicrobial resistance crisis. This review summarizes recent advancements in the field of BEVs to encourage further research into these enigmatic entities. This will facilitate a better understanding of intra- and interkingdom communication phenomena and reveal promising therapeutic approaches.
Assuntos
Bactérias , Disbiose , Vesículas Extracelulares , Microbioma Gastrointestinal , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/metabolismo , Humanos , Bactérias/imunologia , Bactérias/metabolismo , Bactérias/classificação , Animais , Disbiose/microbiologia , Disbiose/imunologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/imunologiaRESUMO
Previous studies have indicated a critical role of intestinal bacteria in the pathogenesis of ulcerative colitis (UC). B. salyersiae is a commensal species from the human gut microbiota. However, what effect it has on UC development has not been investigated. In the present study, we explored this issue and demonstrated for the first time that oral administration of B. salyersiae CSP6, a bacterium previously isolated from the fecal sample of a healthy individual, protected against dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice. In particular, B. salyersiae CSP6 improved mucosal damage and attenuated gut dysbiosis in the colon of DSS-fed mice. Specifically, B. salyersiae CSP6 decreased the population of pathogenic Escherichia-Shigella spp. and increased the abundance of probiotic Dubosiella spp. and Bifidobacterium pseudolongum. Additionally, by reshaping the colonic microbiota, B. salyersiae CSP6 remarkably increased the fecal concentrations of equol, 8-deoxylactucin, and tiglic acid, three beneficial metabolites that have been well documented to exert strong anti-inflammatory effects. Altogether, our study provides novel evidence that B. salyersiae is a candidate probiotic species with potential anti-colitis properties in the human colon, which has applications for the development of next-generation probiotics.
Assuntos
Bacteroides , Colo , Sulfato de Dextrana , Modelos Animais de Doenças , Fezes , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Probióticos , Animais , Probióticos/farmacologia , Humanos , Colo/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Bacteroides/isolamento & purificação , Fezes/microbiologia , Masculino , Colite/microbiologia , Colite/induzido quimicamente , Disbiose/microbiologia , Colite Ulcerativa/microbiologiaRESUMO
Autism Spectrum Disorder (ASD) is a multifactorial disorder involving genetic and environmental factors leading to pathophysiologic symptoms and comorbidities including neurodevelopmental disorders, anxiety, immune dysregulation, and gastrointestinal (GI) abnormalities. Abnormal intestinal permeability has been reported among ASD patients and it is well established that disturbances in eating patterns may cause gut microbiome imbalance (i.e., dysbiosis). Therefore, studies focusing on the potential relationship between gut microbiota and ASD are emerging. We compared the intestinal bacteriome and mycobiome of a cohort of ASD subjects with their non-ASD siblings. Differences between ASD and non-ASD subjects include a significant decrease at the phylum level in Cyanobacteria (0.015% vs. 0.074%, p < 0.0003), and a significant decrease at the genus level in Bacteroides (28.3% vs. 36.8%, p < 0.03). Species-level analysis showed a significant decrease in Faecalibacterium prausnitzii, Prevotella copri, Bacteroides fragilis, and Akkermansia municiphila. Mycobiome analysis showed an increase in the fungal Ascomycota phylum (98.3% vs. 94%, p < 0.047) and an increase in Candida albicans (27.1% vs. 13.2%, p < 0.055). Multivariate analysis showed that organisms from the genus Delftia were predictive of an increased odds ratio of ASD, whereas decreases at the phylum level in Cyanobacteria and at the genus level in Azospirillum were associated with an increased odds ratio of ASD. We screened 24 probiotic organisms to identify strains that could alter the growth patterns of organisms identified as elevated within ASD subject samples. In a preliminary in vivo preclinical test, we challenged wild-type Balb/c mice with Delftia acidovorans (increased in ASD subjects) by oral gavage and compared changes in behavioral patterns to sham-treated controls. An in vitro biofilm assay was used to determine the ability of potentially beneficial microorganisms to alter the biofilm-forming patterns of Delftia acidovorans, as well as their ability to break down fiber. Downregulation of cyanobacteria (generally beneficial for inflammation and wound healing) combined with an increase in biofilm-forming species such as D. acidovorans suggests that ASD-related GI symptoms may result from decreases in beneficial organisms with a concomitant increase in potential pathogens, and that beneficial probiotics can be identified that counteract these changes.
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Transtorno do Espectro Autista , Microbioma Gastrointestinal , Micobioma , Irmãos , Transtorno do Espectro Autista/microbiologia , Humanos , Feminino , Masculino , Criança , Animais , Camundongos , Pré-Escolar , Disbiose/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Candida albicans/isolamento & purificação , Fezes/microbiologiaRESUMO
Introduction. Disruptions in gut microbiota, known as dysbiosis, have been increasingly linked to pathogenic infections, with Salmonella Typhimurium being a notable contributor to these disturbances.Hypothesis. We hypothesize that the S. Typhimurium 14028 WT strain induces significant dysbiosis in the rat gut microbiota and that the dam and seqA genes play crucial roles in this process.Aim. In this study, it was aimed at investigating the dysbiotic activity of the S. Typhimurium 14028 WT strain on the rat gut microbiota and the roles of dam and seqA genes on this activity.Method. Changes in the rat gut microbiota were determined by examining the anal swap samples taken from the experimental groups of these animals using 16S rRNA high-throughput sequencing technology.Results. In the experimental groups, the dominant phyla were determined to be Firmicutes and Bacteroidetes (P<0.05). However, while the rate of Bacteroidetes was significantly reduced in those treated with the WT and seqA mutants, no significant difference was observed in the dam mutant compared to the control group (P<0.05). In all experimental animals, the dominant species was determined to be Prevotella copri, regardless of the experiment time and application. The analysis results of the samples taken on the third day from the rat groups infected with the S. Typhimurium 14028 WT strain (W2) presented the most striking data of this study.Conclusion. Through distance analysis, we demonstrated that a successful Salmonella infection completely changes the composition of the microbiota, dramatically reduces species diversity and richness in the microbiota and encourages the growth of opportunistic pathogens.
Assuntos
Disbiose , Microbioma Gastrointestinal , RNA Ribossômico 16S , Salmonella typhimurium , Animais , Salmonella typhimurium/genética , Salmonella typhimurium/isolamento & purificação , Microbioma Gastrointestinal/genética , Disbiose/microbiologia , Ratos , RNA Ribossômico 16S/genética , Masculino , Mutação , Salmonelose Animal/microbiologia , Proteínas de Bactérias/genética , Ratos Sprague-DawleyRESUMO
Diet is a robust entrainment cue that regulates diurnal rhythms of the gut microbiome. We and others have shown that disruption of the circadian clock drives the progression of colorectal cancer (CRC). While certain bacterial species have been suggested to play driver roles in CRC, it is unknown whether the intestinal clock impinges on the microbiome to accelerate CRC pathogenesis. To address this, genetic disruption of the circadian clock, in an Apc-driven mouse model of CRC, was used to define the impact on the gut microbiome. When clock disruption is combined with CRC, metagenomic sequencing identified dysregulation of many bacterial genera including Bacteroides, Helicobacter, and Megasphaera. We identify functional changes to microbial pathways including dysregulated nucleic acid, amino acid, and carbohydrate metabolism, as well as disruption of intestinal barrier function. Our findings suggest that clock disruption impinges on microbiota composition and intestinal permeability that may contribute to CRC pathogenesis.
Assuntos
Relógios Circadianos , Neoplasias Colorretais , Disbiose , Microbioma Gastrointestinal , Animais , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Disbiose/microbiologia , Camundongos , Relógios Circadianos/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Modelos Animais de Doenças , Humanos , PermeabilidadeRESUMO
Preeclampsia is a multifactorial gestational syndrome characterized by increased blood pressure during pregnancy associated with multiorgan involvement. The impact of this disease on maternal and neonatal health is significant, as it can lead to various fetal comorbidities and contribute to the development of maternal comorbidities later in life. Consistent evidence has shown that the microbiota acts as a regulator of the immune system, and it may, therefore, influence the development of preeclampsia by modulating immune factors. This narrative review aims to investigate the role of the immune system in the pathogenesis of preeclampsia and to summarize the most recent literature on the possible link between preeclampsia and alterations in the intestinal microbiota. To this end, we conducted a literature search, aiming to perform a narrative review, on PubMed and Embase from January 1990 to March 2024, focusing on the latest studies that highlight the main differences in microbial composition between patients with and without preeclampsia, as well as the effects of microbial metabolites on the immune system. From the review of 28 studies assessing the intestinal microbiota in preeclamptic women, preeclampsia could be associated with a state of dysbiosis. Moreover, these patients showed higher plasmatic levels of endotoxin, pro-inflammatory cytokines, and T helper 17 cells; however, the findings on specific microbes and metabolites that could cause immune imbalances in preeclampsia are still preliminary.
Assuntos
Disbiose , Microbioma Gastrointestinal , Pré-Eclâmpsia , Humanos , Pré-Eclâmpsia/microbiologia , Pré-Eclâmpsia/imunologia , Gravidez , Feminino , Microbioma Gastrointestinal/imunologia , Disbiose/imunologia , Disbiose/microbiologia , Citocinas/sangue , Citocinas/metabolismo , Sistema Imunitário/microbiologia , Sistema Imunitário/imunologiaRESUMO
Recent interest in noninvasive diagnostic approaches has highlighted the potential of urinary microbiota as a novel biomarker for bladder cancer. This study investigated the urinary microbiota of 30 bladder cancer patients and 32 healthy controls using a specific NGS protocol that sequences eight hypervariable regions of the 16S rRNA gene, providing detailed insights into urinary microbiota composition. The relative abundance of microbial compositions in urine samples from cancer patients and healthy controls was analyzed across various taxonomic levels. No notable differences were highlighted at the phylum, class, order, and family levels. At the genus level, 53% of detected genera were represented in either cancer patients or healthy controls. Microbial diversity was significantly lower in cancer patients. The differential analysis identified five genera, Rhodanobacter, Cutibacterium, Alloscardovia, Moryella, and Anaeroglobus, that were significantly more abundant in cancer patients. Notably, Rhodanobacter was present in 20 cancer samples but absent in healthy controls. Conversely, 40 genera, including Lactobacillus, Propionibacterium, and Bifidobacterium, exhibited reduced abundance in cancer patients. These findings suggest that some genera may serve as potential biomarkers for bladder cancer, highlighting the need for further research to explore their roles in disease pathogenesis and their potential applications in diagnostics and therapeutics.
Assuntos
Disbiose , Microbiota , RNA Ribossômico 16S , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/urina , Neoplasias da Bexiga Urinária/microbiologia , Neoplasias da Bexiga Urinária/diagnóstico , Masculino , Feminino , Disbiose/microbiologia , Disbiose/urina , Disbiose/diagnóstico , Microbiota/genética , RNA Ribossômico 16S/genética , Pessoa de Meia-Idade , Idoso , Estudos de Casos e Controles , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Adulto , Biomarcadores Tumorais/urinaRESUMO
Follicular skin disorders, including hidradenitis suppurativa (HS), frequently coexist with systemic autoinflammatory diseases, such as inflammatory bowel disease (IBD) and its subtypes, Crohn's disease and ulcerative colitis. Previous studies suggest that dysbiosis of the human gut microbiome may serve as a pathogenic link between HS and IBD. However, the role of the microbiome (gut, skin, and blood) in the context of IBD and various follicular disorders remains underexplored. Here, we performed a systematic review to investigate the relationship between follicular skin disorders, IBD, and the microbiome. Of the sixteen included studies, four evaluated the impact of diet on the microbiome in HS patients, highlighting a possible link between gut dysbiosis and yeast-exclusion diets. Ten studies explored bacterial colonization and HS severity with specific gut and skin microbiota, including Enterococcus and Veillonella. Two studies reported on immunological or serological biomarkers in HS patients with autoinflammatory disease, including IBD, and identified common markers including elevated cytokines and T-lymphocytes. Six studies investigated HS and IBD patients concurrently. Our systematic literature review highlights the complex interplay between the human microbiome, IBD, and follicular disorders with a particular focus on HS. The results indicate that dietary modifications hold promise as a therapeutic intervention to mitigate the burden of HS and IBD. Microbiota analyses and the identification of key serological biomarkers are crucial for a deeper understanding of the impact of dysbiosis in these conditions. Future research is needed to more thoroughly delineate the causal versus associative roles of dysbiosis in patients with both follicular disorders and IBD.
Assuntos
Disbiose , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/microbiologia , Disbiose/microbiologia , Microbiota , Hidradenite Supurativa/microbiologia , Pele/microbiologia , Dermatopatias/microbiologiaRESUMO
BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a common, yet underdiagnosed, gut condition caused by gut dysbiosis. A previous study has shown the potential of herbal therapy, providing equivalent results to rifaximin. OBJECTIVES: The objective of this study was to assess how the use of an oral botanical regimen may modulate the gut microbiome, facial erythema, and intestinal permeability in those with SIBO. METHODS: This was an open-label prospective study of adults that had lactulose breath test-confirmed SIBO. Participants received a 10-week oral supplementation of a Biocidin liquid tincture and GI Detox+. If participants were found to be non-responsive to treatment after 10 weeks with a persistently positive lactulose breath test, a third oral supplement, Olivirex, was administered for an additional 4 weeks. Lactulose breath tests were administered at baseline, weeks 6, 10, and 14 to assess for SIBO status. A high-resolution photographic analysis system was utilized to analyze changes in facial erythema. Stool sample collections and venipuncture were performed to analyze the gut microbiome and intestinal permeability. RESULTS: A total of 33 subjects were screened with breath testing, and 19 subjects were found to have SIBO. Three of the subjects withdrew during the screening period prior to baseline, and sixteen subjects enrolled. Four subjects dropped out after baseline. Hydrogen-dominant SIBO was the most common subtype of SIBO, followed by methane and hydrogen sulfide. The botanical regimen was most effective for hydrogen- and hydrogen sulfide-dominant SIBO, leading to negative breath test results at week 10 in 42.8% and 66.7% of participants, respectively. Compared to baseline, supplementation with the botanical regimen led to positive shifts in short-chain fatty acid-producing bacteria such as A. muciniphila, F. prausnitzii, C. eutectus, and R. faecis by 31.4%, 35.4%, 24.8%, and 48.7% percent at week 10, respectively. The mean abundance of Firmicutes decreased by 20.2%, Bacteroides increased by 30%, and the F/B ratio decreased by 25.4% at week 10 compared to baseline. At week 10, there was a trending 116% increase in plasma LPS/IgG (p = 0.08). There were no significant changes in plasma zonulin, DAO, histamine, DAO/histamine, LPS/IgG, LPS/IgA, or LPS/IgM. Facial erythema was not statistically different at week 6, but at week 10, there was a 20% decrease (p = 0.001) in redness intensity. Among the patients that extended to week 14, there was no statistical change in erythema. CONCLUSIONS: Supplementation with an antimicrobial botanical supplemental regimen may have therapeutic potential in hydrogen and hydrogen-sulfide subtypes of SIBO. Furthermore, the botanical supplemental regimen may reduce facial erythema, increase SCFA-producing bacteria, decrease the F/B ratio, and modulate markers of intestinal permeability.