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1.
Microbiome ; 9(1): 16, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472685

RESUMO

The human gut harbors an enormous number of symbiotic microbes, which is vital for human health. However, interactions within the complex microbiota community and between the microbiota and its host are challenging to elucidate, limiting development in the treatment for a variety of diseases associated with microbiota dysbiosis. Using in silico simulation methods based on flux balance analysis, those interactions can be better investigated. Flux balance analysis uses an annotated genome-scale reconstruction of a metabolic network to determine the distribution of metabolic fluxes that represent the complete metabolism of a bacterium in a certain metabolic environment such as the gut. Simulation of a set of bacterial species in a shared metabolic environment can enable the study of the effect of numerous perturbations, such as dietary changes or addition of a probiotic species in a personalized manner. This review aims to introduce to experimental biologists the possible applications of flux balance analysis in the host-microbiota interaction field and discusses its potential use to improve human health. Video abstract.


Assuntos
Bactérias/metabolismo , Simulação por Computador , Microbioma Gastrointestinal/fisiologia , Interações entre Hospedeiro e Microrganismos , Redes e Vias Metabólicas , Animais , Disbiose/metabolismo , Humanos
2.
Int J Mol Sci ; 22(1)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33375200

RESUMO

Microbiota is defined as the collection of microorganisms within the gastrointestinal ecosystem. These microbes are strongly implicated in the stimulation of immune responses. An unbalanced microbiota, termed dysbiosis, is related to the development of several liver diseases. The bidirectional relationship between the gut, its microbiota and the liver is referred to as the gut-liver axis. The translocation of bacterial products from the intestine to the liver induces inflammation in different cell types such as Kupffer cells, and a fibrotic response in hepatic stellate cells, resulting in deleterious effects on hepatocytes. Moreover, ischemia-reperfusion injury, a consequence of liver surgery, alters the microbiota profile, affecting inflammation, the immune response and even liver regeneration. Microbiota also seems to play an important role in post-operative outcomes (i.e., liver transplantation or liver resection). Nonetheless, studies to determine changes in the gut microbial populations produced during and after surgery, and affecting liver function and regeneration are scarce. In the present review we analyze and discuss the preclinical and clinical studies reported in the literature focused on the evaluation of alterations in microbiota and its products as well as their effects on post-operative outcomes in hepatic surgery.


Assuntos
Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/metabolismo , Hepatopatias/cirurgia , Transplante de Fígado/métodos , Fígado/fisiologia , Animais , Disbiose/metabolismo , Disbiose/microbiologia , Disbiose/fisiopatologia , Trato Gastrointestinal/microbiologia , Hepatectomia/métodos , Humanos , Hepatopatias/fisiopatologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/microbiologia , Traumatismo por Reperfusão/fisiopatologia
3.
Nature ; 585(7826): 509-517, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32968260

RESUMO

Colorectal cancer (CRC) is a heterogeneous disease of the intestinal epithelium that is characterized by the accumulation of mutations and a dysregulated immune response. Up to 90% of disease risk is thought to be due to environmental factors such as diet, which is consistent with a growing body of literature that describes an 'oncogenic' CRC-associated microbiota. Whether this dysbiosis contributes to disease or merely represents a bystander effect remains unclear. To prove causation, it will be necessary to decipher which specific taxa or metabolites drive CRC biology and to fully characterize the underlying mechanisms. Here we discuss the host-microbiota interactions in CRC that have been reported so far, with particular focus on mechanisms that are linked to intestinal barrier disruption, genotoxicity and deleterious inflammation. We further comment on unknowns and on the outstanding challenges in the field, and how cutting-edge technological advances might help to overcome these. More detailed mechanistic insights into the complex CRC-associated microbiota would potentially reveal avenues that can be exploited for clinical benefit.


Assuntos
Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/fisiopatologia , Microbioma Gastrointestinal , Animais , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/terapia , Disbiose/metabolismo , Disbiose/microbiologia , Microbioma Gastrointestinal/imunologia , Humanos , Inflamação/microbiologia , Mutagênese
5.
Nat Commun ; 11(1): 4018, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32782301

RESUMO

The gut microbiome is an ecosystem that involves complex interactions. Currently, our knowledge about the role of the gut microbiome in health and disease relies mainly on differential microbial abundance, and little is known about the role of microbial interactions in the context of human disease. Here, we construct and compare microbial co-abundance networks using 2,379 metagenomes from four human cohorts: an inflammatory bowel disease (IBD) cohort, an obese cohort and two population-based cohorts. We find that the strengths of 38.6% of species co-abundances and 64.3% of pathway co-abundances vary significantly between cohorts, with 113 species and 1,050 pathway co-abundances showing IBD-specific effects and 281 pathway co-abundances showing obesity-specific effects. We can also replicate these IBD microbial co-abundances in longitudinal data from the IBD cohort of the integrative human microbiome (iHMP-IBD) project. Our study identifies several key species and pathways in IBD and obesity and provides evidence that altered microbial abundances in disease can influence their co-abundance relationship, which expands our current knowledge regarding microbial dysbiosis in disease.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/microbiologia , Consórcios Microbianos , Obesidade/microbiologia , Adulto , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Bactérias/metabolismo , Estudos de Coortes , Disbiose/metabolismo , Disbiose/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Especificidade de Hospedeiro , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Obesidade/metabolismo
7.
Arch Biochem Biophys ; 690: 108505, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32679195

RESUMO

Obesity has major adverse consequences on human health contributing to the development of, among others, insulin resistance and type 2 diabetes, cardiovascular disease, non-alcoholic fatty liver disease, altered behavior and cognition, and cancer. Changes in dietary habits and lifestyle could contribute to mitigate the development and/or progression of these pathologies. This review will discuss current evidence on the beneficial actions of the flavan-3-ol (-)-epicatechin (EC) on obesity-associated comorbidities. These benefits can be in part explained through EC's capacity to mitigate several common events underlying the development of these pathologies, including: i) high circulating levels of glucose, lipids and endotoxins; ii) chronic systemic inflammation; iii) tissue endoplasmic reticulum and oxidative stress; iv) insulin resistance; v) mitochondria dysfunction and vi) dysbiosis. The currently known underlying mechanisms and cellular targets of EC's beneficial effects are discussed. While, there is limited evidence from human studies supplementing with pure EC, other studies involving cocoa supplementation in humans, pure EC in rodents and in vitro studies, support a potential beneficial action of EC on obesity-associated comorbidities. This evidence also stresses the need of further research in the field, which would contribute to the development of human dietary strategies to mitigate the adverse consequences of obesity.


Assuntos
Catequina/farmacologia , Obesidade/tratamento farmacológico , Animais , Glicemia/efeitos dos fármacos , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Comorbidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Disbiose/metabolismo , Dislipidemias/metabolismo , Retículo Endoplasmático/metabolismo , Endotoxinas/metabolismo , Flavonoides/farmacologia , Humanos , Inflamação/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos , Transtornos Mentais/complicações , Transtornos Mentais/tratamento farmacológico , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estresse Oxidativo
8.
Am J Gastroenterol ; 115(6): 814-822, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32250997

RESUMO

Primary sclerosing cholangitis (PSC) is a rare, immune-mediated, chronic cholestatic liver disease associated with a unique phenotype of inflammatory bowel disease that frequently manifests as pancolitis with right-sided predominance. Available data suggest a bidirectional interplay of the gut-liver axis with critical roles for the gastrointestinal microbiome and circulating bile acids (BAs) in the pathophysiology of PSC. BAs shape the gut microbiome, whereas gut microbes have the potential to alter BAs, and there are emerging data that alterations of BAs and the microbiome are not simply a consequence but the cause of PSC. Clustering of PSC in families may suggest that PSC occurs in genetically susceptible individuals. After exposure to an environmental trigger (e.g., microbial byproducts or BAs), an aberrant or exaggerated cholangiocyte-induced immune cascade occurs, ultimately leading to bile duct damage and progressive fibrosis. The pathophysiology can be conceptualized as a triad of (1) gut dysbiosis, (2) altered BA metabolism, and (3) immune-mediated biliary injury. Immune activation seems to be central to the disease process, but immunosuppression does not improve clinical outcomes or alter the natural history of PSC. Currently, orthoptic liver transplantation is the only established life-saving treatment, whereas antimicrobial therapy or fecal transplantation is an emerging therapeutic option for PSC. The beneficial effects of these microbiome-based therapies are likely mediated by a shift of the gut microbiome with favorable effects on BA metabolism. In the future, personalized approaches will allow to better target the interdependence between microbiome, immune function, and BA metabolism and potentially cure patients with PSC.


Assuntos
Anti-Infecciosos/uso terapêutico , Ácidos e Sais Biliares/metabolismo , Colangite Esclerosante/terapia , Disbiose/terapia , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/microbiologia , Colangite Esclerosante/imunologia , Colangite Esclerosante/metabolismo , Colangite Esclerosante/microbiologia , Disbiose/imunologia , Disbiose/metabolismo , Transplante de Microbiota Fecal , Humanos , Imunidade nas Mucosas/imunologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Transplante de Fígado
9.
Int J Mol Med ; 45(4): 1130-1140, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32124946

RESUMO

The gut microbiota is important for maintaining the integrity of the intestinal barrier, promoting immunological tolerance and carrying out metabolic activities that have not evolved in hosts. Intestinal dysbiosis is associated with chronic kidney disease and probiotic supplementation has been shown to be beneficial. However, it is not known whether gut microorganisms­specifically, lactic acid bacteria (LAB) can protect against acute kidney injury (AKI). To address this issue, the present study investigated the effects of Lactobacillus salivarius BP121, an intestinal LAB isolated from the feces of newborns, in a rat model of cisplatin­induced AKI and also in Caco­2 human intestinal epithelial cells. BP121 prevented cisplatin­induced AKI in rats, as demonstrated by decreases in inflammation and oxidative stress in kidney tissue and in serum levels of uremic toxins such as indoxyl sulfate (IS) and p­cresol sulfate (PCS). BP121 also reduced intestinal permeability, as determined using fluorescein isothiocyanate­dextran by immunohistochemical detection of tight junction (TJ) proteins such as zona occludens­1 and occludin. The abundance of Lactobacillus spp., which are beneficial intestinal flora, was increased by BP121; this was accompanied by an increase in the concentrations of short­chain fatty acids in feces. Additionally, H2O2­induced TJ protein damage was reduced in Caco­2 cells treated with BP121 culture supernatant, an effect that was reversed by the 5' AMP­activated protein kinase (AMPK) inhibitor Compound C and Toll­like receptor (TLR)4 inhibitor TLR4­IN­C34. In conclusion, this study demonstrated that L. salivarius BP121 protects against cisplatin­induced AKI by decreasing inflammation and oxidative stress and this renoprotective effect is partially mediated by modulating the gut environment and thereby suppressing IS and PCS production as well as by regulating AMPK and TLR4 dependent TJ assembly.


Assuntos
Lesão Renal Aguda , Cisplatino/efeitos adversos , Cresóis/metabolismo , Disbiose , Indicã/metabolismo , Lactobacillus salivarius/metabolismo , Ésteres do Ácido Sulfúrico/metabolismo , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/microbiologia , Lesão Renal Aguda/prevenção & controle , Animais , Células CACO-2 , Cisplatino/farmacologia , Disbiose/induzido quimicamente , Disbiose/metabolismo , Disbiose/mortalidade , Disbiose/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley
10.
Nat Rev Urol ; 17(4): 232-250, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32071434

RESUMO

The female reproductive tract (FRT), similar to other mucosal sites, harbours a site-specific microbiome, which has an essential role in maintaining health and homeostasis. In the majority of women of reproductive age, the microbiota of the lower FRT (vagina and cervix) microenvironment is dominated by Lactobacillus species, which benefit the host through symbiotic relationships. By contrast, the upper FRT (uterus, Fallopian tubes and ovaries) might be sterile in healthy individuals or contain a low-biomass microbiome with a diverse mixture of microorganisms. When dysbiosis occurs, altered immune and metabolic signalling can affect hallmarks of cancer, including chronic inflammation, epithelial barrier breach, changes in cellular proliferation and apoptosis, genome instability, angiogenesis and metabolic dysregulation. These pathophysiological changes might lead to gynaecological cancer. Emerging evidence shows that genital dysbiosis and/or specific bacteria might have an active role in the development and/or progression and metastasis of gynaecological malignancies, such as cervical, endometrial and ovarian cancers, through direct and indirect mechanisms, including modulation of oestrogen metabolism. Cancer therapies might also alter microbiota at sites throughout the body. Reciprocally, microbiota composition can influence the efficacy and toxic effects of cancer therapies, as well as quality of life following cancer treatment. Modulation of the microbiome via probiotics or microbiota transplant might prove useful in improving responsiveness to cancer treatment and quality of life. Elucidating these complex host-microbiome interactions, including the crosstalk between distal and local sites, will translate into interventions for prevention, therapeutic efficacy and toxic effects to enhance health outcomes for women with gynaecological cancers.


Assuntos
Carcinogênese , Disbiose/microbiologia , Neoplasias dos Genitais Femininos/microbiologia , Genitália Feminina/microbiologia , Microbiota/fisiologia , Anti-Infecciosos/uso terapêutico , Bactérias Anaeróbias , Colo do Útero/microbiologia , Disbiose/metabolismo , Estrogênios/metabolismo , Tubas Uterinas/microbiologia , Feminino , Microbioma Gastrointestinal , Neoplasias dos Genitais Femininos/metabolismo , Neoplasias dos Genitais Femininos/prevenção & controle , Neoplasias dos Genitais Femininos/terapia , Genitália Feminina/metabolismo , Humanos , Lactobacillus , Ovário/microbiologia , Probióticos/uso terapêutico , Útero/microbiologia , Vagina/microbiologia
11.
EBioMedicine ; 52: 102649, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32062353

RESUMO

Host-microbiota interactions involving inflammatory and metabolic pathways have been linked to the pathogenesis of multiple immune-mediated diseases and metabolic conditions like diabetes and obesity. Accumulating evidence suggests that alterations in the gut microbiome could play a role in cardiovascular disease. This review focuses on recent advances in our understanding of the interplay between diet, gut microbiota and cardiovascular disease, with emphasis on heart failure and coronary artery disease. Whereas much of the literature has focused on the circulating levels of the diet- and microbiota-dependent metabolite trimethylamine-N-oxide (TMAO), several recent sequencing-based studies have demonstrated compositional and functional alterations in the gut microbiomes in both diseases. Some microbiota characteristics are consistent across several study cohorts, such as a decreased abundance of microbes with capacity for producing butyrate. However, the published gut microbiota studies generally lack essential covariates like diet and clinical data, are too small to capture the substantial variation in the gut microbiome, and lack parallel plasma samples, limiting the ability to translate the functional capacity of the gut microbiomes to actual function reflected by circulating microbiota-related metabolites. This review attempts to give directions for future studies in order to demonstrate clinical utility of the gut-heart axis.


Assuntos
Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/metabolismo , Suscetibilidade a Doenças , Microbioma Gastrointestinal , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Animais , Butiratos/metabolismo , Dieta , Disbiose/metabolismo , Ácidos Graxos Voláteis/biossíntese , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Lipopolissacarídeos/metabolismo , Metagenoma , Metagenômica , Transdução de Sinais
12.
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
13.
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
14.
J Mol Endocrinol ; 64(1): 29-42, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31770101

RESUMO

Diabetic dysbiosis has been described as a novel key player in diabetes and diabetic complications. However, the cellular/molecular alterations associated with dysbiosis remain poorly characterized. For that, control, non-obese type 2 diabetic MKR mice and MKR mice treated with butyrate were used to delineate the epigenetic, cellular and molecular mechanisms by which dysbiosis associated with diabetes induces colon shortening and inflammation attesting to gastrointestinal disturbance. Our results show that dysbiosis is associated with T2DM and characterized by reduced Bacteroid fragilis population and butyrate-forming bacteria. The reduction of butyrate-forming bacteria and inadequate butyrate secretion result in alleviating HDAC3 inhibition and altering colon permeability. The observed changes are also associated with an increase in ROS production, a rise in NOX4 proteins, and a shift in the inflammatory markers, where IL-1ß is increased and IL-10 and IL-17α are reduced. Treatment with butyrate restores the homeostatic levels of NOX4 and IL-1ß. In summary, our data suggest that in T2DM, dysbiosis is associated with a reduction in butyrate content leading to increased HDAC3 activity. Butyrate treatment restores the homeostatic levels of the inflammatory markers and reduces ROS production known to mediate diabetes-induced colon disturbance. Taken together, our results suggest that butyrate could be a potential treatment to attenuate diabetic complications.


Assuntos
Butiratos/farmacologia , Disbiose/tratamento farmacológico , Epigênese Genética/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Diabetes Mellitus , Disbiose/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Espécies Reativas de Oxigênio/metabolismo
16.
Med Hypotheses ; 134: 109436, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31678900

RESUMO

Intestinal dysbiosis refers to an imbalance in the intestinal flora. The concept of small intestinal bacterial overgrowth (SIBO), a condition of abnormal proliferation of the small intestine microbiota, has been proposed as a form of small intestine dysbiosis. In Parkinson's disease patients, weight loss and metabolic disorders such as lipid abnormalities are frequently encountered. This was a prospective investigation of the presence of SIBO using the lactulose breath test, Parkinson's disease symptoms, medications, abdominal symptoms, and blood data involving 39 Parkinson's disease patients. Of the 39 patients, 19 were positive for SIBO, 16 were negative, and 4 were equivocal. SIBO-positive patients had a significantly smaller dopaminergic drug load (dopamine replacement of Parkinson's disease drug potency) (P = 0.009) and significantly lower serum triglyceride (TG) (P = 0.024) and total bilirubin (P = 0.019) levels. No relationship was seen between the presence or absence of SIBO and motor or abdominal symptoms. The following hypothesis was developed with regard to the possibility that intestinal bacterial overgrowth has various effects that are exhibited via bile acid metabolism in Parkinson's disease patients. Serum bilirubin levels become higher as bilirubin metabolism declines with decreases in the intestinal bacteria. At the same time, bile acid is broken down due to increased intestinal bacteria, and lipid absorption decreases. This induces low serum TG levels and leads to weight loss. By a similar mechanism, there is less absorption of vitamin D as bile acid levels decrease, leading to osteoporosis and fractures. The possibility that some of the non-motor manifestations accompanying Parkinson's disease are caused by intestinal dysbiosis needs to be considered.


Assuntos
Ácidos e Sais Biliares/metabolismo , Síndrome da Alça Cega/complicações , Disbiose/complicações , Microbioma Gastrointestinal , Metabolismo dos Lipídeos , Doença de Parkinson/metabolismo , Idoso , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/farmacocinética , Antiparkinsonianos/uso terapêutico , Bilirrubina/sangue , Síndrome da Alça Cega/diagnóstico , Síndrome da Alça Cega/metabolismo , Testes Respiratórios , Disbiose/metabolismo , Feminino , Fraturas Espontâneas/etiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Humanos , Hidrogênio/metabolismo , Absorção Intestinal , Intestino Delgado/microbiologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Osteoporose/etiologia , Doença de Parkinson/microbiologia , Estudos Prospectivos , Triglicerídeos/sangue , Deficiência de Vitamina D/etiologia
17.
Dig Dis Sci ; 65(2): 431-441, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31441001

RESUMO

BACKGROUND: Short bowel syndrome (SBS) resulting from extensive intestinal resection is thought to significantly affect gut microbiota. Data are limited on the signatures of the intestinal microbiome in SBS with different anatomical types. AIMS: The aim of our investigation was to characterize the composition and function of gut microbiota in SBS with or without ileocecal resection (ICR). METHODS: Six-week-old male Sprague-Dawley rats underwent 75% small bowel resection (SBR) with the ileocecal junction intact (SBR group, jejunoileal anastomosis, n = 10) or removed (ICR group, jejunocolic anastomosis, n = 10), or sham surgery (sham group, n = 10). Colonic contents of the rats were collected 28 days after operation, and 16S rRNA gene sequencing was performed on the MiSeq Illumina platform to analyze bacterial composition. RESULTS: Overall structures of the gut microbiome differed significantly among the three groups. The bacterial α-diversity of the ICR group was remarkably lower than that of the sham group. ICR rats were enriched with Lactobacillus and opportunistic pathogens from Proteobacteria but depleted of commensal genera belonging to the Lachnospiraceae, Ruminococcaceae and Erysipelotrichaceae families. Genera from the Bacteroidales S24-7 group, Porphyromonadaceae, Prevotellaceae, Rikenellaceae and Christensenellaceae were prevalent in SBR rats. Functional pathways of branched-chain and aromatic amino acid biosynthesis, lipopolysaccharide biosynthesis and infectious diseases were abundant in the ICR group, while SBR rats featured pathways of C5 branched dibasic acid metabolism, biotin metabolism and one carbon pool folate. CONCLUSIONS: ICR causes dramatically more severe intestinal dysbiosis than SBR only in SBS rat models, resulting in altered functional profiles of the gut microbiome.


Assuntos
Disbiose/microbiologia , Microbioma Gastrointestinal/genética , Síndrome do Intestino Curto/microbiologia , Anastomose Cirúrgica , Animais , Ceco/cirurgia , Clostridiales , Colo/microbiologia , Colo/cirurgia , Disbiose/etiologia , Disbiose/metabolismo , Microbioma Gastrointestinal/fisiologia , Íleo/cirurgia , Jejuno/cirurgia , Lactobacillus , Masculino , Proteobactérias , RNA Ribossômico 16S , Ratos , Índice de Gravidade de Doença , Síndrome do Intestino Curto/complicações , Síndrome do Intestino Curto/metabolismo
19.
Nat Rev Immunol ; 20(1): 40-54, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31388093

RESUMO

Low-grade inflammation is the hallmark of metabolic disorders such as obesity, type 2 diabetes and nonalcoholic fatty liver disease. Emerging evidence indicates that these disorders are characterized by alterations in the intestinal microbiota composition and its metabolites, which translocate from the gut across a disrupted intestinal barrier to affect various metabolic organs, such as the liver and adipose tissue, thereby contributing to metabolic inflammation. Here, we discuss some of the recently identified mechanisms that showcase the role of the intestinal microbiota and barrier dysfunction in metabolic inflammation. We propose a concept by which the gut microbiota fuels metabolic inflammation and dysregulation.


Assuntos
Microbioma Gastrointestinal , Inflamação/microbiologia , Animais , Doença Crônica , Disbiose/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Doenças Metabólicas/microbiologia
20.
Cells ; 8(12)2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31847455

RESUMO

The microbiome is undoubtedly the second genome of the human body and has diverse roles in health and disease. However, translational progress is limited due to the vastness of the microbiome, which accounts for over 3.3 million genes, whose functions are still unclear. Numerous studies in the past decade have demonstrated how microbiome impacts various organ-specific cancers by altering the energy balance of the body, increasing adiposity, synthesizing genotoxins and small signaling molecules, and priming and regulating immune response and metabolism of indigestible dietary components, xenobiotics, and pharmaceuticals. In relation to breast cancer, one of the most prominent roles of the human microbiome is the regulation of steroid hormone metabolism since endogenous estrogens are the most important risk factor in breast cancer development especially in postmenopausal women. Intestinal microbes encode enzymes capable of deconjugating conjugated estrogen metabolites marked for excretion, pushing them back into the enterohepatic circulation in a biologically active form. In addition, the intestinal microbes also break down otherwise indigestible dietary polyphenols to synthesize estrogen-like compounds or estrogen mimics that exhibit varied estrogenic potency. The present account discusses the potential role of gastrointestinal microbiome in breast cancer development by mediating metabolism of steroid hormones and synthesis of biologically active estrogen mimics.


Assuntos
Neoplasias da Mama/microbiologia , Estrogênios/metabolismo , Microbiota/fisiologia , Adiposidade/fisiologia , Neoplasias da Mama/metabolismo , Disbiose/metabolismo , Feminino , Microbioma Gastrointestinal/fisiologia , Humanos , Obesidade/microbiologia , Obesidade/fisiopatologia , Fatores de Risco
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