RESUMO
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
BACKGROUND: This study examines the complex relationships among the neuroendocrine axis, gut microbiome, inflammatory responses, and gastrointestinal symptoms in patients with irritable bowel syndrome (IBS). The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes. AIM: To investigate the interactions between the neuroendocrine axis, gut microbiome, inflammation, and gastrointestinal symptoms in patients with IBS. METHODS: Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study. Healthy individuals undergoing routine check-ups during the same period served as the control group. Data were collected on neuroendocrine hormone levels, gut microbiome profiles, inflammatory biomarkers, and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis. RESULTS: IBS patients exhibited significant dysregulation of the neuroendocrine axis, with altered levels of cortisol, serotonin, and neuropeptides compared to healthy controls. The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera, including Bifidobacterium, Lactobacillus, and Faecalibacterium, which were associated with neuroendocrine disturbances. Additionally, elevated levels of inflammatory markers, such as C-reactive protein, interleukin-6, and tumor necrosis factor-α, were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain, bloating, and altered bowel habits. CONCLUSION: The findings suggest that targeting the neuroendocrine axis, gut microbiome, and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.
Assuntos
Biomarcadores , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Sistemas Neurossecretores , Humanos , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/imunologia , Síndrome do Intestino Irritável/fisiopatologia , Microbioma Gastrointestinal/imunologia , Feminino , Adulto , Masculino , Sistemas Neurossecretores/fisiopatologia , Pessoa de Meia-Idade , Biomarcadores/sangue , Estudos de Casos e Controles , Inflamação/imunologia , Inflamação/microbiologia , Dor Abdominal/microbiologia , Dor Abdominal/etiologia , Dor Abdominal/imunologia , Serotonina/sangue , Serotonina/metabolismo , Adulto JovemRESUMO
Oral cancer is an aggressive and rapidly progressive disease. The oral cavity is home to over 700 species of microorganisms that regulate metabolism, immune function, and health. There are three types of mechanisms by which bacteria may participate in carcinogenesis. First, bacteria cause chronic inflammation, which stimulates the production of cytokines, including interleukins, interferons, and tumor necrosis factor. Second, bacteria can interact directly with host cells by secreting toxins or by binding to membrane receptors. Finally, the production of metabolites by bacteria may also contribute to carcinogenesis. The importance of the bacteria level and composition in the transition of oral precancerous lesions to cancer has been demonstrated. The relationships of changes in microbiome composition with smoking, inflammation in healthy individuals, as well as with the development of oral cancer in patients, have been studied.
Assuntos
Microbiota , Neoplasias Bucais , Boca , Humanos , Neoplasias Bucais/microbiologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Boca/microbiologia , Citocinas/metabolismo , Fumar/efeitos adversos , Inflamação/microbiologia , Carcinogênese , Bactérias/metabolismo , Bactérias/genética , Bactérias/patogenicidade , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/genéticaRESUMO
One in six people are projected to be 65 years or older by 2050. As the population ages, better treatments for injuries that disproportionately impact the aged population will be needed. Clinical studies show that people aged 65 and older experience higher rates of morbidity and mortality after burn injury, including a greater incidence of pulmonary complications when compared to younger burn injured adults, which we and others believe is mediated, in part, by inflammation originating in the intestines. Herein, we use our clinically relevant model of scald burn injury in young and aged mice to determine whether cohousing aged mice with young mice or giving aged mice oral gavage of fecal material from young mice is sufficient to alter the microbiome of the aged mice and protect them from inflammation in the ileum and the lungs. Aged burn injured mice have less DNA expression of Bacteroidetes in the feces and an unhealthy Firmicutes/Bacteroidetes ratio. Both Bacteroidetes and the ratio of these two phyla are restored in aged burn injured by prior cohousing for a month with younger mice but not fecal transfer from young mice. This shift in the microbiome coincides with heightened expression of danger-associated molecular patterns (DAMP), and pro-inflammatory cytokine interleukin-6 (il6) in the ileum and lung of aged, burn injured mice, and heightened antimicrobial peptide camp in the lung. Cohousing reverses DAMP expression in the ileum and lung, and cathelicidin-related antimicrobial peptide protein (camp) in the lung, while fecal transfer heightened DAMPs while reducing camp in the lung, and also increased IL-6 protein in the lungs. These results highlight the importance of the intestinal microbiome in mediating inflammation within the gut-lung axis, giving insights into potential future treatments in the clinic.
Assuntos
Queimaduras , Microbioma Gastrointestinal , Inflamação , Animais , Queimaduras/microbiologia , Camundongos , Inflamação/microbiologia , Camundongos Endogâmicos C57BL , Masculino , Envelhecimento , Fezes/microbiologia , Pulmão/microbiologia , Pulmão/metabolismo , Pulmão/patologia , Transplante de Microbiota Fecal , Bacteroidetes , Íleo/microbiologia , Íleo/metabolismoRESUMO
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
The oral microbiome is a diverse ecosystem containing a community of symbiotic, commensal, and pathogenic microorganisms. One key microorganism linked to periodontal disease (PD) is Porphyromonas gingivalis (P. gingivalis), a Gram-negative anaerobic bacterium known to have several virulence factors that trigger inflammation and immune evasion. On the other hand, Akkermansia muciniphila (A. muciniphila), a symbiotic bacterium, has been recently shown to play an important role in mitigating inflammation and reducing periodontal damage. In vivo and in vitro studies have shown that A. muciniphila decreases inflammatory mediators and improves immune responses, suggesting its role in mitigating PD and related inflammatory systemic conditions such as diabetes, hypertension, and obesity. This review discusses the anti-inflammatory effects of A. muciniphila, its impact on periodontal health, and its potential role in managing systemic diseases. The overall aim is to elucidate how this bacterium might help reduce inflammation, improve oral health, and influence broader health outcomes.
Assuntos
Akkermansia , Saúde Bucal , Doenças Periodontais , Humanos , Doenças Periodontais/microbiologia , Doenças Periodontais/prevenção & controle , Boca/microbiologia , Inflamação/microbiologia , Porphyromonas gingivalis/patogenicidade , Probióticos , Verrucomicrobia , Microbiota , AnimaisRESUMO
In recent years, the association of the microbiome with various diseases has been reported. The oral and gut microbiomes have been linked to cerebral aneurysms and are involved in the systemic inflammatory response, which is mediated mainly via the immune system. Chronic inflammation plays an important role in the pathogenesis and rupture of cerebral aneurysms, and the microbiome is potentially involved in this process. Moreover, the gut microbiome is involved in acute brain injury following subarachnoid hemorrhage. Thus, further studies on microbiome-targeted treatments for cerebral aneurysm are required.
Assuntos
Microbioma Gastrointestinal , Aneurisma Intracraniano , Aneurisma Intracraniano/microbiologia , Humanos , Boca/microbiologia , Microbiota , Inflamação/microbiologiaRESUMO
Persistent colonization and outgrowth of potentially pathogenic organisms in the intestine can result from long-term antibiotic use or inflammatory conditions, and may perpetuate dysregulated immunity and tissue damage1,2. Gram-negative Enterobacteriaceae gut pathobionts are particularly recalcitrant to conventional antibiotic treatment3,4, although an emerging body of evidence suggests that manipulation of the commensal microbiota may be a practical alternative therapeutic strategy5-7. Here we isolated and down-selected commensal bacterial consortia from stool samples from healthy humans that could strongly and specifically suppress intestinal Enterobacteriaceae. One of the elaborated consortia, comprising 18 commensal strains, effectively controlled ecological niches by regulating gluconate availability, thereby re-establishing colonization resistance and alleviating Klebsiella- and Escherichia-driven intestinal inflammation in mice. Harnessing these activities in the form of live bacterial therapies may represent a promising solution to combat the growing threat of proinflammatory, antimicrobial-resistant Enterobacteriaceae infection.
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Enterobacteriaceae , Fezes , Microbioma Gastrointestinal , Klebsiella , Simbiose , Animais , Camundongos , Humanos , Feminino , Klebsiella/isolamento & purificação , Fezes/microbiologia , Masculino , Infecções por Enterobacteriaceae/microbiologia , Inflamação/microbiologia , Inflamação/imunologia , Intestinos/microbiologia , Camundongos Endogâmicos C57BLRESUMO
The gut microbiota is one of the most critical factors in human health. It involves numerous physiological processes impacting host health, mainly via immune system modulation. A balanced microbiome contributes to the gut's barrier function, preventing the invasion of pathogens and maintaining the integrity of the gut lining. Dysbiosis, or an imbalance in the gut microbiome's composition and function, disrupts essential processes and contributes to various diseases. This narrative review summarizes key findings related to the gut microbiota in modern multifactorial inflammatory conditions such as ulcerative colitis or Crohn's disease. It addresses the challenges posed by antibiotic-driven dysbiosis, particularly in the context of C. difficile infections, and the development of novel therapies like fecal microbiota transplantation and biotherapeutic drugs to combat these infections. An emphasis is given to restoration of the healthy gut microbiome through dietary interventions, probiotics, prebiotics, and novel approaches for managing gut-related diseases.
Assuntos
Disbiose , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Obesidade , Probióticos , Humanos , Disbiose/microbiologia , Disbiose/terapia , Obesidade/microbiologia , Probióticos/uso terapêutico , Animais , Inflamação/microbiologia , Prebióticos/administração & dosagemRESUMO
The human gastrointestinal tract hosts a complex and dynamic community of microorganisms known as the gut microbiota, which play a pivotal role in numerous physiological processes, including digestion, metabolism, and immune function. Recent research has highlighted the significant impact of diet on the gut microbiota composition and functionality, and the consequential effects on host health. Concurrently, there is growing evidence linking the gut microbiota to inflammation, a key factor in many chronic diseases such as inflammatory bowel disease (IBD), obesity, diabetes, and cardiovascular diseases (CVDs). This review explores how dietary components influence the gut microbiota composition, how these microbial changes affect inflammatory pathways, and the therapeutic implications of modulating this axis for chronic inflammatory disease prevention and management. Beneficial dietary patterns, such as the Mediterranean diet (MD) and plant-based diets, promote a diverse and balanced gut microbiota composition, supporting anti-inflammatory pathways. Conversely, the Western diet (WD), high in saturated fats and refined sugars, is associated with dysbiosis and increased inflammation. With all the links between the three variables considered, this review attempts to offer a thorough examination of the triangle formed by inflammation, the gut microbiota, and food.
Assuntos
Dieta , Microbioma Gastrointestinal , Inflamação , Humanos , Inflamação/microbiologia , Disbiose/microbiologia , Animais , Dieta Mediterrânea , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/etiologia , Dieta Ocidental/efeitos adversosRESUMO
Gut microbiota is an indispensable commensal partner of human superorganism. The wealth of genetic repertoire provided by these microorganisms extends host's substrate processing capability. Energy and nutrient harvesting machinery primarily depends on the proper function of these organisms. However, the dynamic composition of microbiota changes with age, lifestyle, stress factors, infections, medications, and host pathophysiological conditions. Host immune system is primarily responsible for shaping up the microbial community and sustaining the symbiotic state. This involves controlling the delicate balance between agility toward pathobionts and tolerance toward symbionts. When things go wrong with this crosstalk, dysbiosis may arise.Metabolic syndrome is a multisystemic, low-grade chronic inflammatory disease that involves dyslipidemia, glucose intolerance, insulin resistance, and central obesity. Excess caloric intake with high-sugar and high-fat diet promote high energy harvesting and lipogenesis. The secretion of adipokines accompanies lipid spillover from fat cells, which contribute to insulin resistance and the expansion of adipose tissue in ectopic sites. Proinflammatory cytokines from adipose tissue macrophages increase the extent of adipose dysfunction.The inflammatory nature of obesity and metabolic syndrome recall the connection between dysbiosis and immune dysfunction. A remarkable association exits between obesity, inflammatory bowel disease, gluten-sensitive enteropathy, and dysbiosis. These conditions compromise the gut mucosa barrier and allow lipopolysaccharide to enter circulation. Unresolved chronic inflammation caused by one condition may overlap or trigger the other(s). Experimental studies and therapeutic trials of fecal microbiota transplantation promise limited improvement in some of these conditions.Typically, metabolic syndrome is considered as a consequence of overnutrition and the vicious cycle of lipogenesis, lipid accumulation, and chronic low-level inflammation. Because of the complex nature of this disorder, it remains inconclusive whether dysbiosis is a cause or consequence of obesity and metabolic syndrome.
Assuntos
Disbiose , Microbioma Gastrointestinal , Síndrome Metabólica , Obesidade , Humanos , Microbioma Gastrointestinal/fisiologia , Síndrome Metabólica/microbiologia , Síndrome Metabólica/metabolismo , Obesidade/microbiologia , Obesidade/metabolismo , Animais , Metabolismo dos Lipídeos , Inflamação/metabolismo , Inflamação/microbiologia , Tecido Adiposo/metabolismo , Tecido Adiposo/imunologiaRESUMO
Inflammatory bowel diseases (IBD) etiology is multifactorial. Luminal microRNAs (miRNAs) have been suspected to play a role in the promotion of chronic inflammation, but the extent to which fecal miRNAs are interacting with the intestinal ecosystem in a way that contribute to diseases, including IBD, remains unknown. Here, fecal let-7b and miR-21 were found elevated, associated with inflammation, and correlating with multiple bacteria in IBD patients and IL-10-/- mice, model of spontaneous colitis. Using an in vitro microbiota modeling system, we revealed that these two miRNAs can directly modify the composition and function of complex human microbiota, increasing their proinflammatory potential. In vivo investigations revealed that luminal increase of let-7b drastically alters the intestinal microbiota and enhances macrophages' associated proinflammatory cytokines (TNF, IL-6, and IL-1ß). Such proinflammatory effects are resilient and dependent on the bacterial presence. Moreover, we identified that besides impairing the intestinal barrier function, miR-21 increases myeloperoxidase and antimicrobial peptides secretion, causing intestinal dysbiosis. More importantly, in vivo inhibition of let-7b and miR-21 with anti-miRNAs significantly improved the intestinal mucosal barrier function and promoted a healthier host-microbiota interaction in the intestinal lining, which altogether conferred protection against colitis. In summary, we provide evidence of the functional significance of fecal miRNAs in host-microbiota communication, highlighting their therapeutic potential in intestinal inflammation and dysbiosis-related conditions, such as IBD.
Assuntos
Colite , Fezes , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Humanos , Fezes/microbiologia , Camundongos , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Colite/microbiologia , Colite/induzido quimicamente , Colite/genética , Inflamação/microbiologia , Inflamação/metabolismo , Disbiose/microbiologia , Camundongos Endogâmicos C57BL , Feminino , Camundongos Knockout , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Masculino , Mucosa Intestinal/microbiologia , Mucosa Intestinal/metabolismo , Citocinas/metabolismo , Macrófagos/imunologia , Macrófagos/microbiologia , Macrófagos/metabolismo , Modelos Animais de Doenças , Interleucina-10/genética , Interleucina-10/metabolismoRESUMO
BACKGROUND: The nasopharynx serves as a crucial niche for the microbiome of the upper respiratory tract. However, the association between the intratumoral microbiota and host systemic inflammation and immune status in nasopharyngeal carcinoma (NPC) remain uncertain. METHODS: We performed 5R 16S rDNA sequencing on NPC tissue samples, followed by diversity analysis, LEfSe differential analysis, and KEGG functional prediction. The analyses were based on indices such as AISI, SIRI, PAR, PLR, and NAR. Correlation analyses between microbes and these indices were performed to identify microbes associated with inflammation and immune status. Additionally, regression analysis based on tumor TNM stage was performed to identify key microbes linked to tumor progression. The head and neck squamous cell carcinoma (HNSC) transcriptome and the paired HNSC microbiome data from TCGA were utilized to validate the analyses. RESULTS: The Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes were the most enriched phyla in NPC tissues. Microbes within these phyla demonstrated high sensitivity to changes in host systemic inflammation and immune status. Proteobacteria and Firmicutes showed significant differences between inflammation groups. Actinobacteria varied specifically with platelet-related inflammatory indices, and Bacteroidetes genera exhibited significant differences between NAR groups. Corynebacterium and Brevundimonas significantly impacted the T stage of tumors, with a high load of Corynebacterium within tumors associated with a better prognosis CONCLUSION: Our analysis indicates that Proteobacteria play a crucial role in the inflammatory state of NPC, while Bacteroidetes are more sensitive to the tumor immune status.
Assuntos
Inflamação , Microbiota , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/microbiologia , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/microbiologia , Microbiota/imunologia , Masculino , Inflamação/imunologia , Inflamação/microbiologia , Feminino , Pessoa de Meia-Idade , Adulto , RNA Ribossômico 16S/genética , Bactérias/classificação , Bactérias/imunologia , Bactérias/genética , Bactérias/isolamento & purificação , IdosoRESUMO
OBJECTIVE: Gut microbes and microbe-dependent metabolites (eg, tryptophan-kynurenine-serotonin pathway metabolites) have been linked to systemic inflammation, but the microbiota-metabolite-inflammation axis remains uncharacterised in children. Here we investigated whether gut microbiota features and circulating metabolites (both microbe-dependent and non-microbe-dependent metabolites) associated with circulating inflammation markers in children. METHODS: We studied children from the prospective Gen3G birth cohort who had data on untargeted plasma metabolome (n=321 children; Metabolon platform), gut microbiota (n=147; 16S rRNA sequencing), and inflammation markers (plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1, and tumour necrosis factor-α) measured at 5-7 years. We examined associations of microbial taxa and metabolites-examining microbe-dependent and non-microbe-dependent metabolites separately-with each inflammatory marker and with an overall inflammation score (InfSc), adjusting for key confounders and correcting for multiple comparisons. We also compared the proportion of significantly associated microbe-dependent versus non-microbe-dependent metabolites, identified a priori (Human Microbial Metabolome Database), with each inflammation marker. RESULTS: Of 335 taxa tested, 149 were associated (qFDR<0.05) with at least one inflammatory marker; 10 of these were robust to pseudocount choice. Several bacterial taxa involved in tryptophan metabolism were associated with inflammation, including kynurenine-degrading Ruminococcus, which was inversely associated with all inflammation markers. Of 1037 metabolites tested, 315 were previously identified as microbe dependent and were more frequently associated with PAI-1 and the InfSc than non-microbe dependent metabolites. In total, 87 metabolites were associated (qFDR<0.05) with at least one inflammation marker, including kynurenine (positively), serotonin (positively), and tryptophan (inversely). CONCLUSION: A distinct set of gut microbes and microbe-dependent metabolites, including those involved in the tryptophan-kynurenine-serotonin pathway, may be implicated in inflammatory pathways in childhood.
Assuntos
Biomarcadores , Microbioma Gastrointestinal , Inflamação , Metaboloma , Inibidor 1 de Ativador de Plasminogênio , Humanos , Microbioma Gastrointestinal/fisiologia , Criança , Feminino , Masculino , Inflamação/microbiologia , Inflamação/sangue , Biomarcadores/sangue , Estudos Prospectivos , Pré-Escolar , Inibidor 1 de Ativador de Plasminogênio/sangue , Metaboloma/fisiologia , Triptofano/sangue , Triptofano/metabolismo , Cinurenina/sangue , Cinurenina/metabolismo , Fator de Necrose Tumoral alfa/sangue , RNA Ribossômico 16S/genética , Quimiocina CCL2/sangueRESUMO
Alterations in intestinal permeability and the gut microbiome caused by alcohol abuse are associated with alcoholic liver disease and with worsening of inflammatory bowel diseases (IBD) symptoms. To resolve the direct effects of chronic ethanol consumption on the colon and its microbiome in the absence of acute or chronic alcohol-induced liver disease, we developed a mouse model of chronic binge drinking that uncovers how alcohol may enhance susceptibility to colitis via the microbiota. Employing daily ethanol gavage, we recapitulate key features of binge ethanol consumption. We found that binge ethanol drinking worsens intestinal infection, colonic injury and inflammation, and this effect persists beyond the drinking period. Using gnotobiotics, we showed that alcohol-driven susceptibility to colitis is microbiota-dependent and transferable to ethanol-naïve mice by microbiome transplantation. Allobaculum spp. expanded in binge drinking mice, and administration of Allobaculum fili was sufficient to enhance colitis in non-drinking mice. Our study provides a model to study binge drinking-microbiota interactions and their effects on host disease and reinforces the pathogenic function of Allobaculum spp. as colitogenic bacteria. Our findings illustrate how chronic binge drinking-induced alterations of the microbiome may affect susceptibility to IBD onset or flares.
Assuntos
Consumo Excessivo de Bebidas Alcoólicas , Colite , Colo , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Animais , Consumo Excessivo de Bebidas Alcoólicas/complicações , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Colite/microbiologia , Colite/induzido quimicamente , Colo/microbiologia , Colo/patologia , Modelos Animais de Doenças , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Etanol/efeitos adversos , Suscetibilidade a Doenças , Masculino , Vida Livre de Germes , Inflamação/microbiologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologiaRESUMO
Many cattle infected with Mycoplasma bovis remain healthy while others develop severe chronic respiratory disease. We hypothesized that inflammatory stimuli such as co-pathogens worsen disease outcomes in M. bovis-infected calves. Calves (n=24) were intrabronchially inoculated with M. bovis and either killed bacterial lysate, transient M. haemolytica infection, or saline. Caseonecrotic lesions developed in 7/7 animals given M. haemolytica and M. bovis compared to 2/8 given M. bovis with no inflammatory stimulus, and 6/9 animals given bacterial lysate and M. bovis (P=0.01). Animals receiving M. haemolytica and M. bovis had more caseonecrotic foci in lungs than those receiving M. bovis with no inflammatory stimulus (median = 21 vs 0; P = 0.01), with an intermediate response (median = 5) in animals given bacterial lysate. In addition to caseonecrotic foci, infected animals developed neutrophilic bronchiolitis that appeared to develop into caseonecrotic foci, peribronchiolar lymphocytic cuffs that were not associated with the other lesions, and 4 animals with bronchiolitis obliterans. The data showed that transient lung inflammation at the time of M. bovis infection provoked the development of caseonecrotic bronchopneumonia, and the severity of inflammation influenced the number of caseonecrotic foci that developed. In contrast, caseonecrotic lesions were few or absent in M. bovis-infected calves without a concurrent inflammatory stimulus. These studies provide insight into how caseonecrotic lesions develop within the lung of M. bovis-infected calves. This and other studies suggest that controlling co-pathogens and harmful inflammatory responses in animals infected with M. bovis could potentially minimize development of M. bovis caseonecrotic bronchopneumonia.
Assuntos
Doenças dos Bovinos , Pulmão , Mycoplasma bovis , Pneumonia por Mycoplasma , Animais , Bovinos , Pneumonia por Mycoplasma/veterinária , Pneumonia por Mycoplasma/microbiologia , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/imunologia , Pulmão/microbiologia , Pulmão/patologia , Inflamação/veterinária , Inflamação/microbiologia , Mannheimia haemolytica/patogenicidade , Coinfecção/veterinária , Coinfecção/microbiologiaRESUMO
As part of its pathogenesis, Salmonella enterica serovar Typhimurium delivers effector proteins into host cells. One effector is SspH2, a member of the so-called novel E3 ubiquitin ligase family, that interacts with and enhances, NOD1 pro-inflammatory signaling, though the underlying mechanisms are unclear. Here, we report that SspH2 interacts with multiple members of the NLRC family to enhance pro-inflammatory signaling by targeted ubiquitination. We show that SspH2 modulates host innate immunity by interacting with both NOD1 and NOD2 in mammalian epithelial cell culture via the NF-κB pathway. Moreover, purified SspH2 and NOD1 directly interact, where NOD1 potentiates SspH2 E3 ubiquitin ligase activity. Mass spectrometry and mutational analyses identified four key lysine residues in NOD1 that are required for its enhanced activation by SspH2, but not its basal activity. These critical lysine residues are positioned in the same region of NOD1 and define a surface on the receptor that appears to be targeted by SspH2. Overall, this work provides evidence for post-translational modification of NOD1 by ubiquitin and uncovers a unique mechanism of spatially selective ubiquitination to enhance the activation of an archetypal NLR.
Assuntos
Proteína Adaptadora de Sinalização NOD1 , Salmonella typhimurium , Transdução de Sinais , Ubiquitinação , Proteína Adaptadora de Sinalização NOD1/metabolismo , Proteína Adaptadora de Sinalização NOD1/genética , Humanos , Salmonella typhimurium/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Proteína Adaptadora de Sinalização NOD2/metabolismo , Proteína Adaptadora de Sinalização NOD2/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Células HEK293 , Imunidade Inata , Inflamação/metabolismo , Inflamação/microbiologia , NF-kappa B/metabolismo , Infecções por Salmonella/metabolismo , Infecções por Salmonella/microbiologia , Infecções por Salmonella/imunologiaRESUMO
Glaesserella parasuis (GPS) can cause severe systemic inflammation in pigs, resulting in huge economic losses to the pig industry. At present, no effective method is available for the prevention and control of GPS infection. Molecular breeding for disease resistance is imminent, but disease-resistance genes have not been identified. To study the mechanism of systemic acute inflammation caused by GPS, we established three in vitro infection models (3D4/21 cells, PK15 cells, and PAVEC cells) according to its infection path. There was no significant difference in apoptosis among the three kinds of cells after 12 h of continuous GPS stimulation, while inflammatory factors were significantly upregulated. Subsequent transcriptome analysis revealed 1969, 1207, and 3564 differentially expressed genes (DEGs) in 3D4/21 cells, PK15 cells, and PAVEC cells, respectively, after GPS infection. Many of the DEGs were predicted to be associated with inflammatory responses (C3, CD44, etc.); cell proliferation, growth and apoptosis; gene expression; and protein phosphorylation. Key signaling pathways, including S100 family signaling, bacteria and virus recognition, and pathogen-induced cytokine storm signaling, were enriched based on Ingenuity Pathway Analysis (IPA). Furthermore, a total of three putative transmembrane receptors and two putative G-protein-coupled receptors, namely F3, ICAM1, PLAUR, ACKR3, and GPRC5A, were identified by IPA among the three types of cells. ACKR3 and GPRC5A play pivotal roles in bacterial adhesion, invasion, host immune response and inflammatory response through the S100 family signaling pathway. Our findings provide new insights into the pathological mechanisms underlying systemic inflammation caused by GPS infection in pigs, and they lay a foundation for further research on disease-resistance breeding to GPS.
Assuntos
Haemophilus parasuis , Inflamação , Transdução de Sinais , Doenças dos Suínos , Animais , Suínos , Haemophilus parasuis/genética , Haemophilus parasuis/patogenicidade , Transdução de Sinais/genética , Inflamação/genética , Inflamação/microbiologia , Doenças dos Suínos/microbiologia , Doenças dos Suínos/genética , Doenças dos Suínos/imunologia , Infecções por Haemophilus/veterinária , Infecções por Haemophilus/genética , Infecções por Haemophilus/microbiologia , Infecções por Haemophilus/imunologia , Transcriptoma/genética , Perfilação da Expressão Gênica , Linhagem Celular , Apoptose/genéticaRESUMO
BACKGROUND: Fatigue and gastrointestinal (GI) distress are common among athletes with an estimated 30-90% of athletes participating in marathons, triathlons, or similar events experiencing GI complaints. Intense exercise can lead to increased intestinal permeability, potentially allowing members of the gut microbiota to permeate into the bloodstream, resulting in an inflammatory response and cascade of performance-limiting outcomes. Probiotics, through their capacity to regulate the composition of the gut microbiota, may act as an adjunctive therapy by enhancing GI and immune function while mitigating inflammatory responses. This review investigates the effectiveness of probiotic supplementation on fatigue, inflammatory markers, and exercise performance based on randomized controlled trials (RCTs). METHODS: This review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and PICOS (Population, Intervention, Comparison, Outcome, Study design) framework. A comprehensive search was conducted in Sportdiscus, PubMed, and Scopus databases, and the screening of titles, abstracts, and full articles was performed based on pre-defined eligibility criteria. Of the 3505 records identified, 1884 were screened using titles and abstracts, of which 450 studies were selected for full-text screening. After final screening, 13 studies met the eligibility criteria and were included for review. The studies contained 513 participants, consisting of 351 males and 115 females, however, two studies failed to mention the sex of the participants. Among the participants, 246 were defined as athletes, while the remaining participants were classified as recreationally active (n = 267). All trials were fully described and employed a double- or triple-blind placebo-controlled intervention using either a single probiotic strain or a multi-strain synbiotic (containing both pro- and pre-biotics). RESULTS: This review assesses the effects of daily probiotic supplementation, ranging from 13 to 90 days, on physical performance and physiological markers in various exercise protocols. Ten studies reported improvements in various parameters, such as, enhanced endurance performance, improved anxiety and stress levels, decreased GI symptoms, and reduced upper respiratory tract infections (URTI). Moreover, despite no improvements in maximal oxygen uptake (VO2), several studies demonstrated that probiotic supplementation led to amelioration in lactate, creatine kinase (CK), and ammonia concentrations, suggesting beneficial effects on mitigating exercise-induced muscular stress and damage. CONCLUSION: Probiotic supplementation, specifically at a minimum dosage of 15 billion CFUs daily for a duration of at least 28 days, may contribute to the reduction of perceived or actual fatigue.