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1.
Adv Exp Med Biol ; 1191: 155-167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32002928

RESUMO

Anxiety disorders are a complex set of illnesses in which genetic factors, particularly stress, play a role in the etiopathogenesis. In recent years, inflammation and intestinal microbiota have also been included in this complex network of relationships. The functions associated with tryptophan catabolism and serotonin biosynthesis have long been associated with anxiety disorders. Tryptophan catabolism progresses toward the path of the kynurenine in the presence of stress and inflammation. The catabolism of kynurenine is a pathway in which many enzymes play a role and a large number of catabolites with neuroactive properties occur. The body's serotonin biosynthesis is primarily performed by enterochromaffin cells located in the intestines. A change in the intestinal microbiota composition (dysbiosis) directly affects the serotonin biosynthesis. Stress, unhealthy nutrition, and the use of antibiotics cause dysbiosis. In the light of this new perspective, the role of dysbiosis-induced inflammation and kynurenine pathway catabolites activated sequentially come into prominence in the etiopathogenesis of anxiety disorders.


Assuntos
Transtornos de Ansiedade/metabolismo , Transtornos de Ansiedade/fisiopatologia , Encéfalo/fisiopatologia , Microbioma Gastrointestinal , Cinurenina/metabolismo , Disbiose/metabolismo , Disbiose/microbiologia , Humanos , Serotonina/biossíntese , Serotonina/metabolismo
2.
Zool Res ; 41(1): 20-31, 2020 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31930784

RESUMO

There is a growing appreciation for the specific health benefits conferred by commensal microbiota on their hosts. Clinical microbiota analysis and animal studies in germ-free or antibiotic-treated mice have been crucial for improving our understanding of the role of the microbiome on the host mucosal surface; however, studies on the mechanisms involved in microbiome-host interactions remain limited to small animal models. Here, we demonstrated that rhesus monkeys under short-term broad-spectrum antibiotic treatment could be used as a model to study the gut mucosal host-microbiome niche and immune balance with steady health status. Results showed that the diversity and community structure of the gut commensal bacteria in rhesus monkeys were both disrupted after antibiotic treatment. Furthermore, the 16S rDNA amplicon sequencing results indicated that Escherichia-Shigella were predominant in stool samples 9 d of treatment, and the abundances of bacterial functional genes and predicted KEGG pathways were significantly changed. In addition to inducing aberrant morphology of small intestinal villi, the depletion of gut commensal bacteria led to increased proportions of CD3 + T, CD4 + T, and CD16 + NK cells in peripheral blood mononuclear cells (PBMCs), but decreased numbers of Treg and CD20 + B cells. The transcriptome of PBMCs from antibiotic-treated monkeys showed that the immune balance was affected by modulation of the expression of many functional genes, including IL-13, VCAM1, and LGR4.


Assuntos
Disbiose/imunologia , Microbioma Gastrointestinal , Intestinos/anatomia & histologia , Macaca mulatta/microbiologia , Animais , Antibacterianos/farmacologia , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , DNA Bacteriano/genética , Fezes/microbiologia , Intestinos/microbiologia , Masculino
3.
J Agric Food Chem ; 68(3): 779-787, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31894986

RESUMO

The chain length of fructan determines its different physiological effects. This study is to explore the effects of low-performance inulin [LPI, degree of polymerization (DP) ≤ 9] and high-performance inulin (HPI, DP ≥ 23) on obesity-associated liver injury of high-fat diet (HFD) feeding mice and its underlying mechanism. Eight weeks of supplementation of C57BL/6J mice with HPI, relative to LPI (p < 0.05), caused the more efficient improvement against the HFD-induced liver insulin resistance through activating IRS1/PI3K/Akt pathway and reduced protein expressions of inflammatory factors nuclear factor-kappaB (NF-κB) and interleukin-6 (IL-6) in the liver. HPI exhibited the more positive effects on liver steatosis by inhibiting acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and sterol regulatory element binding protein 1 (SREBP1) in comparison with LPI (p < 0.05). HPI also increased acetic acid, propionic acid, and butyric acid levels in the colon of HFD-fed mice (p < 0.05). Compared to LPI, HPI feeding of HFD-fed mice led to the more effective decrease in the Firmicutes abundance from 72.1% to 34.5%, but a more significant increase in the Bacteroidetes population from 19.8 to 57.1% at the phyla level, and increased the abundance of Barnesiella, Bacteroides, and Parabacteroides at the genus level (p < 0.05). Depending on DP, HPI exerts the more positive regulation on liver injury and gut microbiota dysfunction than LPI.


Assuntos
Disbiose/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Inulina/administração & dosagem , Inulina/química , Fígado/lesões , Obesidade/tratamento farmacológico , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais/análise , Disbiose/genética , Disbiose/metabolismo , Disbiose/microbiologia , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , NF-kappa B/genética , NF-kappa B/metabolismo , Obesidade/genética , Obesidade/metabolismo , Obesidade/microbiologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Polimerização
4.
Cell Host Microbe ; 27(1): 11-13, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31951821

RESUMO

The neonatal gut microbiome undergoes dynamic changes in response to many nutritional and environmental variables. A recent study by Singer et al. in Nature Medicine elucidates several mechanisms to inhibit the expansion of gut-derived pathobionts in a dysbiotic neonatal gut and prevent these pathobionts from disseminating systemically and causing sepsis in neonatal mice.


Assuntos
Microbioma Gastrointestinal , Sepse , Animais , Animais Recém-Nascidos , Disbiose , Camundongos
5.
Scand J Immunol ; 91(1): e12805, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31267543

RESUMO

Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease caused by a mutation in the WAS gene that encodes the WAS protein (WASp); up to 5-10% of these patients develop inflammatory bowel disease (IBD). The mechanisms by which WASp deficiency causes IBD are unclear. Intestinal microbial dysbiosis and imbalances in host immune responses play important roles in the pathogenesis of polygenetic IBD; however, few studies have conducted detailed examination of the microbial alterations and their relationship with IBD in WAS. Here, we collected faecal samples from 19 children (all less than 2 years old) with WAS and samples from WASp-KO mice with IBD and subjected them to 16S ribosomal RNA sequencing. We found that microbial community richness and structure in WAS children were different from those in controls; WAS children revealed reduced microbial community richness and diversity. Relative abundance of Bacteroidetes and Verrucomicrobiain in WAS children was significantly lower, while that of Proteobacteria was markedly higher. WASp-KO mice revealed a significantly decreased abundance of Firmicutes. Faecal microbial dysbiosis caused by WASp deficiency is similar to that observed for polygenetic IBD, suggesting that WASp may play crucial function in microbial homoeostasis and that microbial dysbiosis may contribute to IBD in WAS. These microbial alterations may be useful targets for monitoring and therapeutically managing intestinal inflammation in WAS.


Assuntos
Disbiose , Fezes/microbiologia , Microbioma Gastrointestinal , Síndrome de Wiskott-Aldrich/etiologia , Animais , Biodiversidade , Biomarcadores , Estudos de Casos e Controles , Pré-Escolar , Modelos Animais de Doenças , Feminino , Humanos , Lactente , Doenças Inflamatórias Intestinais/etiologia , Masculino , Metagenoma , Metagenômica/métodos , Camundongos , Camundongos Knockout , Mutação , RNA Ribossômico 16S/genética , Síndrome de Wiskott-Aldrich/diagnóstico , Proteína da Síndrome de Wiskott-Aldrich/deficiência
7.
Gut ; 69(1): 62-73, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30923071

RESUMO

OBJECTIVE: The intestinal lumen contains several proteases. Our aim was to determine the role of faecal proteases in mediating barrier dysfunction and symptoms in IBS. DESIGN: 39 patients with IBS and 25 healthy volunteers completed questionnaires, assessments of in vivo permeability, ex vivo colonic barrier function in Ussing chambers, tight junction (TJ) proteins, ultrastructural morphology and 16 s sequencing of faecal microbiota rRNA. A casein-based assay was used to measure proteolytic activity (PA) in faecal supernatants (FSNs). Colonic barrier function was determined in mice (ex-germ free) humanised with microbial communities associated with different human PA states. RESULTS: Patients with IBS had higher faecal PA than healthy volunteers. 8/20 postinfection IBS (PI-IBS) and 3/19 constipation- predominant IBS had high PA (>95th percentile). High-PA patients had more and looser bowel movements, greater symptom severity and higher in vivo and ex vivo colonic permeability. High-PA FSNs increased paracellular permeability, decreased occludin and increased phosphorylated myosin light chain (pMLC) expression. Serine but not cysteine protease inhibitor significantly blocked high-PA FSN effects on barrier. The effects on barrier were diminished by pharmacological or siRNA inhibition of protease activated receptor-2 (PAR-2). Patients with high-PA IBS had lower occludin expression, wider TJs on biopsies and reduced microbial diversity than patients with low PA. Mice humanised with high-PA IBS microbiota had greater in vivo permeability than those with low-PA microbiota. CONCLUSION: A subset of patients with IBS, especially in PI-IBS, has substantially high faecal PA, greater symptoms, impaired barrier and reduced microbial diversity. Commensal microbiota affects luminal PA that can influence host barrier function.


Assuntos
Síndrome do Intestino Irritável/fisiopatologia , Serina Proteases/fisiologia , Adulto , Animais , Biópsia , Células CACO-2 , Estudos de Casos e Controles , Colo/patologia , Disbiose/enzimologia , Fezes/enzimologia , Feminino , Microbioma Gastrointestinal , Humanos , Absorção Intestinal/fisiologia , Mucosa Intestinal/metabolismo , Síndrome do Intestino Irritável/enzimologia , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Permeabilidade , Estudos Prospectivos , Proteólise , Índice de Gravidade de Doença , Proteínas de Junções Íntimas/metabolismo
8.
BJOG ; 127(2): 300, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31446672
9.
Gut ; 69(1): 92-102, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31003979

RESUMO

OBJECTIVE: Patients with primary sclerosing cholangitis (PSC) were previously shown to display a bacterial gut dysbiosis but fungal microbiota has never been examined in these patients. The aim of this study was to assess the fungal gut microbiota in patients with PSC. DESIGN: We analysed the faecal microbiota of patients with PSC and concomitant IBD (n=27), patients with PSC and no IBD (n=22), patients with IBD and no PSC (n=33) and healthy subjects (n=30). Bacterial and fungal composition of the faecal microbiota was determined using 16S and ITS2 sequencing, respectively. RESULTS: We found that patients with PSC harboured bacterial dysbiosis characterised by a decreased biodiversity, an altered composition and a decreased correlation network density. These alterations of the microbiota were associated with PSC, independently of IBD status. For the first time, we showed that patients with PSC displayed a fungal gut dysbiosis, characterised by a relative increase in biodiversity and an altered composition. Notably, we observed an increased proportion of Exophiala and a decreased proportion of Saccharomyces cerevisiae. Compared with patients with IBD and healthy subjects, the gut microbiota of patients with PSC exhibited a strong disruption in bacteria-fungi correlation network, suggesting an alteration in the interkingdom crosstalk. CONCLUSION: This study demonstrates that bacteria and fungi contribute to gut dysbiosis in PSC.


Assuntos
Colangite Esclerosante/microbiologia , Disbiose/microbiologia , Fungos/isolamento & purificação , Microbioma Gastrointestinal , Adulto , Idoso , Bactérias/classificação , Bactérias/isolamento & purificação , Técnicas de Tipagem Bacteriana/métodos , Biodiversidade , Feminino , Fungos/classificação , Humanos , Doenças Inflamatórias Intestinais/microbiologia , Masculino , Pessoa de Meia-Idade , Técnicas de Tipagem Micológica/métodos , Adulto Jovem
10.
Gut ; 69(1): 42-51, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31036757

RESUMO

BACKGROUND AND AIMS: Prenatal and early life bacterial colonisation is thought to play a major role in shaping the immune system. Furthermore, accumulating evidence links early life exposures to the risk of developing IBD later in life. We aimed to assess the effect of maternal IBD on the composition of the microbiome during pregnancy and on the offspring's microbiome. METHODS: We prospectively examined the diversity and taxonomy of the microbiome of pregnant women with and without IBD and their babies at multiple time points. We evaluated the role of maternal IBD diagnosis, the mode of delivery, antibiotic use and feeding behaviour on the microbiome composition during early life. To assess the effects of IBD-associated maternal and infant microbiota on the enteric immune system, we inoculated germ-free mice (GFM) with the respective stool and profiled adaptive and innate immune cell populations in the murine intestines. RESULTS: Pregnant women with IBD and their offspring presented with lower bacterial diversity and altered bacterial composition compared with control women and their babies. Maternal IBD was the main predictor of the microbiota diversity in the infant gut at 7, 14, 30, 60 and 90 days of life. Babies born to mothers with IBD demonstrated enrichment in Gammaproteobacteria and depletion in Bifidobacteria. Finally, GFM inoculated with third trimester IBD mother and 90-day infant stools showed significantly reduced microbial diversity and fewer class-switched memory B cells and regulatory T cells in the colon. CONCLUSION: Aberrant gut microbiota composition persists during pregnancy with IBD and alters the bacterial diversity and abundance in the infant stool. The dysbiotic microbiota triggered abnormal imprinting of the intestinal immune system in GFM.


Assuntos
Microbioma Gastrointestinal/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Complicações na Gravidez/microbiologia , Efeitos Tardios da Exposição Pré-Natal/microbiologia , Imunidade Adaptativa , Adulto , Animais , Bactérias/classificação , Bactérias/isolamento & purificação , Disbiose/imunologia , Disbiose/microbiologia , Transplante de Microbiota Fecal/métodos , Fezes/microbiologia , Feminino , Seguimentos , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Vida Livre de Germes , Humanos , Recém-Nascido , Doenças Inflamatórias Intestinais/imunologia , Masculino , Troca Materno-Fetal , Gravidez , Complicações na Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Estudos Prospectivos
13.
BJOG ; 127(2): 287-299, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31299136

RESUMO

BACKGROUND: Vaginal probiotics claiming to cure and/or prevent bacterial and/or fungal vaginal dysbiosis are available on the market but, until recently, did not have to be approved as drugs for human use. OBJECTIVES: We evaluated the impact of vaginal probiotics on bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) cure and/or recurrence, as well as vaginal microbiota (VMB) composition and vaginal detection of probiotic strains. SEARCH STRATEGY: We performed a systematic literature search in MEDLINE and Embase up to 15 January 2019. SELECTION CRITERIA: There were no restrictions in probiotic strains/formulations, study populations, and designs. BV had to be diagnosed by Nugent or Ison-Hay Gram stain scoring, VVC by culture, wet mount or PCR, and VMB composition/detection by molecular techniques. DATA COLLECTION AND ANALYSIS: The authors independently extracted data. MAIN RESULTS: All 22 vaginal probiotics evaluated in the 34 eligible studies contained Lactobacillus strains, and some contained additional active ingredients. The probiotics hold promise for BV cure and prevention, but much less so for VVC cure and prevention. No major safety concerns were reported in any of the studies. Vaginal detection of probiotic strains never lasted long beyond the dosing period, suggesting that they did not colonise the vagina. However, findings are not definitive because heterogeneity was high and the quality of most studies suboptimal. CONCLUSIONS: Availability of vaginal probiotics for vaginal health indications will likely decline in 2020 because of regulatory changes. We urge the field to invest in clinical evidence-based product development and to conduct future trials more rigorously. TWEETABLE ABSTRACT: Lactobacilli-containing vaginal probiotics hold promise for bacterial vaginosis cure and prevention, but not for vulvovaginal candidiasis.


Assuntos
Candidíase Vulvovaginal , Disbiose/prevenção & controle , Disbiose/terapia , Lactobacillus , Microbiota , Probióticos/administração & dosagem , Vagina/microbiologia , Vaginose Bacteriana , Candidíase Vulvovaginal/microbiologia , Candidíase Vulvovaginal/prevenção & controle , Candidíase Vulvovaginal/terapia , Disbiose/microbiologia , Feminino , Humanos , Resultado do Tratamento , Vaginose Bacteriana/microbiologia , Vaginose Bacteriana/prevenção & controle , Vaginose Bacteriana/terapia
15.
Br Dent J ; 227(12): 1041, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31873262
16.
Medicine (Baltimore) ; 98(51): e18396, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861004

RESUMO

Hydrogen formed by small intestinal bacterial overgrowth in patients with non-constipated irritable bowel syndrome has an inverse relationship with obesity. However, the effect of eradicating small intestinal hydrogen-producing bacterial overgrowth on the body weight of these patients has not yet been reported. The aim of this study was to investigate body weight changes after eradicating small intestinal bacterial overgrowth with rifaximin treatment in patients with non-constipated irritable bowel syndrome.We reviewed the charts of patients with non-constipated irritable bowel syndrome who showed abdominal symptoms with documented lactulose hydrogen breath test results in order to diagnose small intestinal bacterial overgrowth. A total of 153 patients were enrolled in the study and divided into quartiles according to body mass index (BMI) and body weight.In the lowest body weight quartile, the BMI and body weight were significantly increased (0.4 kg/m, P = .038; 0.6 kg, P = .010, respectively) in patients with negative lactulose hydrogen breath tests after rifaximin treatment. However, there was no significant change in body weight in the other quartiles. Despite treatment with rifaximin for 12 weeks, there was no change in BMI or body weight in any group of patients with consistently positive lactulose hydrogen breath tests.Eradication of hydrogen formed by small intestinal bacterial overgrowth does not cause clinically significant changes in body weight.


Assuntos
Antibacterianos/uso terapêutico , Peso Corporal/efeitos dos fármacos , Disbiose/tratamento farmacológico , Enteropatias/tratamento farmacológico , Rifaximina/uso terapêutico , Antibacterianos/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rifaximina/farmacologia
17.
Gan To Kagaku Ryoho ; 46(12): 1807-1813, 2019 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-31879393

RESUMO

Various microbes having been living in our intestine and forming the gut microbiome. When dysbiosis which is typically characterized by reduced microbial diversity occurs, many types of diseases are triggered in our bodies. Recently, relationship between gut microbiome and our immune function are discovered gradually. From this view point, the gut microbiome may have an influence on cancer medicine such as development, therapy(immune checkpoint blockade or chemotherapy), and therapeutic toxicity. In real clinical practice, this influence is reported in some cases such as colorectal cancer and other malignancies. In the near future, the approach from gut microbiome may be a clue to improve the existent cancer diagnosis and therapy. In addition, the modulation of gut microbiome in itself, for example fecal microbiota transplant(FMT), probiotics, and limited usage of antibiotics, is expected to be hints for cancer medicine, though this is not yet established and further studies are needed.


Assuntos
Microbioma Gastrointestinal , Disbiose , Transplante de Microbiota Fecal , Humanos , Sistema Imunitário
18.
BMC Complement Altern Med ; 19(1): 329, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752807

RESUMO

BACKGROUND: Ulcerative colitis (UC) is a modern refractory disease, and its etiology has been difficult to discern. Studies have shown that UC is closely associated with the gut microbiota. Garidisan is composed of wild poppy and Artemisia frigida Willd and is commonly used for the treatment of UC in Inner Mongolia, China. In clinical settings, Garidisan has been found to treat UC effectively, with low recurrence. Previous studies have shown that Garidisan has a good therapeutic effect on mice with UC, but the therapeutic mechanism is still unclear. In this study, we investigated the regulatory effect of Garidisan on dysbiosis of the gut microbiota in a UC mouse model and explored the possible mechanism of the therapeutic effect of Garidisan on UC. METHODS: The UC mouse model was established by the dextran sulfate sodium (DSS) circulating free water drinking method, and the luminal contents were sampled under sterile conditions. High-throughput sequencing of the 16S rRNA gene V3 + V4 region of the luminal contents of the control group, model group, and Garidisan group was conducted, and clustering of operational taxonomic units (OTUs) and species annotation were performed. The differences in species composition and microbial community structure between individual groups of samples were analyzed using MetaStat, LefSe, rank sum test, and Bayesian causal network analysis. RESULTS: The UC mouse model was successfully established and the sequencing results were of adequate quality. There were significant differences in the diversity of luminal contents between the control group, model group, and Garidisan group, and the differences between groups were greater than those within any group. The therapeutic effect of Garidisan on UC is attributed to the direct effect on the Lachnospiraceae family of bacteria. CONCLUSION: Garidisan has a good regulatory effect on the gut microbiota, and Lachnospiraceae could be an important direct target of Garidisan for the treatment of UC.


Assuntos
Colite Ulcerativa/microbiologia , Disbiose/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Bactérias/classificação , Bactérias/genética , Sulfato de Dextrana , Modelos Animais de Doenças , Masculino , Medicina Tradicional do Leste Asiático , Camundongos , Camundongos Endogâmicos C57BL
19.
Environ Pollut ; 255(Pt 3): 113357, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31671369

RESUMO

Gut microbiota is of critical importance to host health. Aryl hydrocarbon receptor (AhR) is found to be closely involved in the regulation of gut microbial dynamics. However, it is still not clear how AhR signaling shapes the gut microbiota. In the present study, adult zebrafish were acutely exposed to an AhR antagonist (CH223191), an AhR agonist (polychlorinated biphenyl 126; PCB126) or their combination for 7 d. Overall intestinal health and gut microbial community were temporally monitored (1 d, 3 d and 7 d) and inter-compared among different groups. The results showed that single exposure to PCB126 significantly disrupted the overall health of intestines (i.e., neural signaling, inflammation, epithelial barrier integrity, oxidative stress). However, CH223191 failed to inhibit but enhanced the physiological toxicities of PCB126, implying the involvement of extra mechanisms rather than AhR in the regulation of intestinal physiological activities. Dysbiosis of gut microbiota was also caused by PCB126 over time as a function of sex. It is intriguing that CH223191 successfully abolished the holistic effects of dioxin on gut microbiota, which inferred that growth of gut microbes was directly controlled by AhR activation without the involvement of host feedback modulation. When coming to detailed alterations at certain taxon, both antagonistic and synergistic interactions existed between CH223191 and dioxin, depending on fish sex, exposure duration and bacterial species. Correlation analysis found that gut inflammation was positively associated with pathogenic Legionella bacteria, but was negatively associated with epithelial barrier integrity, suggesting that integral intestinal epithelial barrier can prevent the influx of pathogenic bacteria to induce inflammatory response. Overall, this study has deciphered, for the first time, the direct regulative effects of AhR activity on gut microbiota. Future research is warranted to elucidate the specific mechanisms of AhR action on certain bacterial population.


Assuntos
Dioxinas/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Bactérias/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Disbiose , Intestinos , Microbiota , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais , Peixe-Zebra/metabolismo
20.
Nat Med ; 25(11): 1772-1782, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31700190

RESUMO

Late-onset sepsis (LOS) is thought to result from systemic spread of commensal microbes from the intestines of premature infants. Clinical use of probiotics for LOS prophylaxis has varied owing to limited efficacy, reflecting an incomplete understanding of relationships between development of the intestinal microbiome, neonatal dysbiosis and LOS. Using a model of LOS, we found that components of the developing microbiome were both necessary and sufficient to prevent LOS. Maternal antibiotic exposure that eradicated or enriched transmission of Lactobacillus murinus exacerbated and prevented disease, respectively. Prophylactic administration of some, but not all Lactobacillus spp. was protective, as was administration of Escherichia coli. Intestinal oxygen level was a major driver of colonization dynamics, albeit via mechanisms distinct from those in adults. These results establish a link between neonatal dysbiosis and LOS, and provide a basis for rational selection of probiotics that modulate primary succession of the microbiome to prevent disease.


Assuntos
Disbiose/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Sepse/tratamento farmacológico , Idade de Início , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Disbiose/microbiologia , Disbiose/prevenção & controle , Humanos , Recém-Nascido Prematuro , Camundongos , Probióticos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Sepse/microbiologia , Sepse/prevenção & controle
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