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1.
J Dairy Sci ; 105(10): 7865-7877, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36055856

RESUMO

The by-products of milk fermentation by lactic acid bacteria provide potential health benefits to the balance of host intestinal microflora. In this study, the anti-inflammatory properties of fatty acids from monoculture-strain (Lactiplantibacillusplantarum A3) and multiple-strain (Streptococcus thermophilus, Lactobacillus bulgaricus, and L. plantarum A3 1:1:2) fermented milk were evaluated in a mouse model of dextran sulfate sodium-induced colitis, and the gut microbiota regulation properties of the fatty acids were also investigated. Results showed that fatty acids can attenuate the inflammatory response by inhibiting the expression of inflammatory factors IL-6 and tumor necrosis factor-α, and blocking the phosphorylation of the JNK in MAPK signal pathway. In addition, the relative abundance of the taxa Akkermansia and Lactobacillus were both enriched after the fatty acid intervention. This finding suggests that fatty acids from the milk fermentation with mixed lactic acid bacteria starters can reduce the severity of dextran sulfate sodium-induced colitis and enhance the abundance of the probiotics in the mice intestinal tract.


Assuntos
Colite , Microbioma Gastrointestinal , Doenças dos Roedores , Animais , Anti-Inflamatórios/metabolismo , Colite/induzido quimicamente , Colite/veterinária , Colo/microbiologia , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Leite/metabolismo , Doenças dos Roedores/metabolismo , Doenças dos Roedores/patologia , Fator de Necrose Tumoral alfa/metabolismo
2.
Front Cell Infect Microbiol ; 12: 921075, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36017369

RESUMO

In most cases, recurrent chronic colitis is caused by the recurrence of acute colitis after incomplete recovery and re-exposure to irritating factors, and the gut microbiome, which is the largest micro-ecosystem in the human body, plays a crucial role in the development of colitis. Plant polysaccharides have always been reported to have the ability for anti-inflammation, and they are closely related to the gut microbiome. Lycium barbarum Glycopeptide (LbGP), the most potent component obtained by further isolation and purification from Lycium barbarum fruit, has been shown to inhibit inflammation in animal models. However, its therapeutic efficacy in colitis and its mechanism in gut microbiota regulation have not been fully studied. In our study, the dextran sulfate sodium (DSS)-induced mouse model was used to dynamically evaluate the effect of LbGP in the treatment of acute colitis and the mechanism from the perspective of the gut microbiome through the 16S rDNA sequence. The results showed that LbGP treatment significantly alleviated acute colitis and improved the gut microbiome compared with that in the model group. Harmful bacteria, such as Lachnoclostridium spp. and Parabacteroides_distasonis, were inhibited and probiotics, such as Bacteroides_acidifaciens, Lactobacillus spp., Turicibacter spp., and Alistipes spp., were increased by LbGP treatment. Further, a Random Forest analysis with 10-fold cross-validation identified a family named Muribaculaceae representing colitis development and recovery upon LbGP treatment. In conclusion, our study demonstrated the capability of LbGP to prevent the development of acute colitis by regulating the composition and diversity of the gut microbiota and highlighted the dynamic process of gut microbiota with the colitis progression. Further, it provides evidence to develop LbGP as a functional food supplement and future drug acting on intestinal disease.


Assuntos
Colite , Microbioma Gastrointestinal , Lycium , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/prevenção & controle , Colo/microbiologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Ecossistema , Glicopeptídeos , Humanos , Lycium/química , Camundongos , Camundongos Endogâmicos C57BL
3.
Cell Rep ; 40(7): 111191, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35977500

RESUMO

Psoriasis has long been associated with inflammatory bowel disease (IBD); however, a causal link is yet to be established. Here, we demonstrate that imiquimod-induced psoriasis (IMQ-pso) in mice disrupts gut homeostasis, characterized by increased proportions of colonic CX3CR1hi macrophages, altered cytokine production, and bacterial dysbiosis. Gut microbiota from these mice produce higher levels of succinate, which induce de novo proliferation of CX3CR1hi macrophages ex vivo, while disrupted gut homeostasis primes IMQ-pso mice for more severe colitis with dextran sulfate sodium (DSS) challenge. These results demonstrate that changes in the gut environment in psoriasis lead to greater susceptibility to IBD in mice, suggesting a two-hit requirement, that is, psoriasis-induced altered gut homeostasis and a secondary environmental challenge. This may explain the increased prevalence of IBD in patients with psoriasis.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Psoríase , Animais , Colo/microbiologia , Sulfato de Dextrana , Modelos Animais de Doenças , Disbiose/complicações , Imiquimode/efeitos adversos , Doenças Inflamatórias Intestinais/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Psoríase/induzido quimicamente
4.
J Microbiol Biotechnol ; 32(7): 877-884, 2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35791078

RESUMO

Probiotics are microorganisms that can benefit host health when ingested in a live state, and lactic acid bacteria are the most common type. Among fungi, Saccharomyces boulardii (SB) is the only strain known to have a probiotic function with beneficial effects on colitis; however, information on other probiotic yeast strains is limited. Therefore, this study aimed to discover yeast strains expressing intestinal anti-inflammatory activities by exhibiting probiotic properties in dextran sodium sulfate (DSS)-induced colitis mice model. Nuruk (Korean traditional fermentation starter) containing various microbial strains was used as a source for yeast strains, and S. cerevisiae 28-7 (SC28-7) strain was selected with in vitro and in vivo characteristics to enable survival in the intestines. After 14 days of pretreatment with the yeast strains, DSS was co-administered for six days to induce colitis in mice. The results revealed that the disease activity index score was lowered by SC28-7 treatment compared to the DSS group, and the colon length and weight/length ratio were recovered in a pattern similar to that of the normal group. SC28-7 administration significantly reduced the secretion of pro-inflammatory cytokines in the serum and modified the mRNA expression of inflammatory cytokines (interleukin-1ß, transforming growth factor-ß, and interferon-γ) and proteins involved in gut barrier functions (mucin 2, mucin 3, zonula occludens-1, and occludin) in colon tissues. These results indicate that SC28-7 attenuates DSS-induced colon damage and inflammation, supporting its future use as a probiotic yeast for treating and preventing intestinal inflammatory diseases such as inflammatory bowel disease.


Assuntos
Colite , Probióticos , Saccharomyces boulardii , Animais , Colite/induzido quimicamente , Colite/metabolismo , Colite/terapia , Colo/microbiologia , Citocinas/metabolismo , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Probióticos/farmacologia , Saccharomyces cerevisiae/metabolismo
5.
Proc Natl Acad Sci U S A ; 119(28): e2114931119, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35787046

RESUMO

The genetic composition of the gut microbiota is constantly reshaped by ecological and evolutionary forces. These strain-level dynamics are challenging to understand because they depend on complex spatial growth processes that take place within a host. Here we introduce a population genetic framework to predict how stochastic evolutionary forces emerge from simple models of microbial growth in spatially extended environments like the intestinal lumen. Our framework shows how fluid flow and longitudinal variation in growth rate combine to shape the frequencies of genetic variants in simulated fecal samples, yielding analytical expressions for the effective generation times, selection coefficients, and rates of genetic drift. We find that over longer timescales, the emergent evolutionary dynamics can often be captured by well-mixed models that lack explicit spatial structure, even when there is substantial spatial variation in species-level composition. By applying these results to the human colon, we find that continuous fluid flow and simple forms of wall growth alone are unlikely to create sufficient bottlenecks to allow large fluctuations in mutant frequencies within a host. We also find that the effective generation times may be significantly shorter than expected from traditional average growth rate estimates. Our results provide a starting point for quantifying genetic turnover in spatially extended settings like the gut microbiota and may be relevant for other microbial ecosystems where unidirectional fluid flow plays an important role.


Assuntos
Microbioma Gastrointestinal , Evolução Biológica , Colo/microbiologia , Ecossistema , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Humanos
6.
Proc Natl Acad Sci U S A ; 119(29): e2205574119, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35858331

RESUMO

Intestinal barrier immunity is essential for controlling gut microbiota without eliciting harmful immune responses, while its defect contributes to the breakdown of intestinal homeostasis and colitis development. Chemerin, which is abundantly expressed in barrier tissues, has been demonstrated to regulate tissue inflammation via CMKLR1, its functional receptor. Several studies have reported the association between increased expression of chemerin-CMKLR1 and disease severity and immunotherapy resistance in inflammatory bowel disease (IBD) patients. However, the pathophysiological role of endogenous chemerin-CMKLR1 signaling in intestinal homeostasis remains elusive. We herein demonstrated that deficiency of chemerin or intestinal epithelial cell (IEC)-specific CMKLR1 conferred high susceptibility to microbiota-driven neutrophilic colon inflammation and subsequent tumorigenesis in mice following epithelial injury. Unexpectedly, we found that lack of chemerin-CMKLR1 signaling specifically reduced expression of lactoperoxidase (LPO), a peroxidase that is predominantly expressed in colonic ECs and utilizes H2O2 to oxidize thiocyanates to the antibiotic compound, thereby leading to the outgrowth and mucosal invasion of gram-negative bacteria and dysregulated CXCL1/2-mediated neutrophilia. Importantly, decreased LPO expression was causally linked to aggravated microbiota-driven colitis and associated tumorigenesis, as LPO supplementation could completely rescue such phenotypes in mice deficient in epithelial chemerin-CMKLR1 signaling. Moreover, epithelial chemerin-CMKLR1 signaling is necessary for early host defense against bacterial infection in an LPO-dependent manner. Collectively, our study reveals that the chemerin-CMKLR1/LPO axis represents an unrecognized immune mechanism that potentiates epithelial antimicrobial defense and restricts harmful colonic neutrophilia and suggests that LPO supplementation may be beneficial for microbiota dysbiosis in IBD patients with a defective innate antimicrobial mechanism.


Assuntos
Carcinogênese , Quimiocinas , Colite , Colo , Microbioma Gastrointestinal , Peptídeos e Proteínas de Sinalização Intercelular , Lactoperoxidase , Receptores de Quimiocinas , Animais , Carcinogênese/imunologia , Transformação Celular Neoplásica , Quimiocinas/genética , Quimiocinas/metabolismo , Colite/imunologia , Colite/microbiologia , Colo/imunologia , Colo/microbiologia , Peróxido de Hidrogênio/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Lactoperoxidase/metabolismo , Camundongos , Neutrófilos/imunologia , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo
7.
Wiad Lek ; 75(5 pt 2): 1323-1327, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35758452

RESUMO

OBJECTIVE: The aim: Study the effect of antibiotics of different groups on the condition of the colon microflora in infants with acute respiratory pathology. PATIENTS AND METHODS: Materials and methods: 140 infants with acute respiratory pathology were examined. Clinical, laboratory and instrumental examination, assessment of the functional state of all organs and systems, chest x ray, clinical signs of the colon microbiocenosis violation, analysis of bacteriological examination and immunological studies of local colon immunity (immunoglobulin concentration (sIgA, IgA, IgG, IgM) in coprofiltrates) were done. RESULTS: Results: The negative effect of antibiotics of different pharmacological groups on the colon microflora state in infants with acute respiratory diseases has been established. The indigenous microflora of the colon is most inhibited by drugs from the group of 3rd generation cephalosporins, aminoglycosides and their combination. While cephalosporins 1-2nd generations, penicillins and macrolides to a lesser extent affect the state of the microbiocenosis of the colon. The use of two courses of antibacterial therapy to a greater extent disrupts the microbiocenosis of the colon in the examined children, compared with one course of therapy. In commune acquired pneumonia and acute complicated bronchiolitis in infants on the background of antibiotic therapy there is a probable decrease in secretory immunoglobulin in coprofiltrate (sIgA), compared with healthy children (p <0.05). CONCLUSION: Conclusions: The analysis of the obtained results showed that antibiotic therapy negatively affects not only the condition of the colon microflora in the examined children, but also suppresses humoral factors of local immunity of the colonic mucosa. Key words: digestive tract microbiocenosis, antibiotic therapy, children.


Assuntos
Antibacterianos , Colo , Antibacterianos/uso terapêutico , Cefalosporinas , Criança , Colo/microbiologia , Humanos , Imunoglobulina A Secretora , Lactente , Mucosa Intestinal
8.
Science ; 377(6601): eabp9960, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35771903

RESUMO

Changes in the composition of the gut microbiota are associated with many human diseases. So far, however, we have failed to define homeostasis or dysbiosis by the presence or absence of specific microbial species. The composition and function of the adult gut microbiota is governed by diet and host factors that regulate and direct microbial growth. The host delivers oxygen and nitrate to the lumen of the small intestine, which selects for bacteria that use respiration for energy production. In the colon, by contrast, the host limits the availability of oxygen and nitrate, which results in a bacterial community that specializes in fermentation for growth. Although diet influences microbiota composition, a poor diet weakens host control mechanisms that regulate the microbiota. Hence, quantifying host parameters that control microbial growth could help define homeostasis or dysbiosis and could offer alternative strategies to remediate dysbiosis.


Assuntos
Bactérias , Colo , Disbiose , Microbioma Gastrointestinal , Homeostase , Intestino Delgado , Bactérias/metabolismo , Colo/microbiologia , Colo/fisiopatologia , Disbiose/microbiologia , Disbiose/fisiopatologia , Interações entre Hospedeiro e Microrganismos , Humanos , Intestino Delgado/microbiologia , Intestino Delgado/fisiopatologia , Nitratos/metabolismo , Oxigênio/metabolismo
9.
Microbiol Spectr ; 10(4): e0065722, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-35730951

RESUMO

Inflammatory bowel disease (IBD) has become a global public health problem. Although the pathogenesis of the disease is unknown, a potential association between the gut microbiota and inflammatory signatures has been established. Probiotics, especially Lactobacillus or Bifidobacterium, are orally taken as food supplements or microbial drugs by patients with IBD or gastrointestinal disorders due to their safety, efficacy, and power to restore the gut microenvironment. In the current study, we investigated the comprehensive effects of probiotic bacterial consortia consisting of Lactobacillus reuteri, Lactobacillus gasseri, Lactobacillus acidophilus (Lactobacillus spp.), and Bifidobacterium lactis (Bifidobacterium spp.) or their metabolites in a dextran sodium sulfate (DSS)-induced colitis mouse model. Our data demonstrate that probiotic consortia not only ameliorate the disease phenotype but also restore the composition and structure of the gut microbiota. Moreover, the effect of probiotic consortia is better than that of any single probiotic strain. The results also demonstrate that mixed fermentation metabolites are capable of ameliorating the symptoms of gut inflammation. However, the administration of metabolites is not as effective as probiotic consortia with respect to phenotypic characteristics, such as body weight, disease activity index (DAI), and histological score. In addition, mixed metabolites led only to changes in intestinal flora composition. In summary, probiotic consortia and metabolites could exert protective roles in the DSS-induced colitis mouse model by reducing inflammation and regulating microbial dysbiosis. These findings from the current study provide support for the development of probiotic-based microbial products as an alternative therapeutic strategy for IBD. IMPORTANCE IBD is a chronic nonspecific inflammatory disease. IBD is characterized by a wide range of lesions, often involving the entire colon, and is characterized mainly by ulcers and erosions of the colonic mucosa. In the present study, we investigated the efficacy of probiotics on the recovery of gut inflammation and the restoration of gut microecology. We demonstrate that probiotic consortia have a superior effect in inhibiting inflammation and accelerating recovery compared with the effects observed in the control group or groups administered with a single strain. These results support the utilization of probiotic consortia as an alternative therapeutic approach to treat IBD.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Probióticos , Animais , Bifidobacterium/fisiologia , Colite/tratamento farmacológico , Colite/terapia , Colo/microbiologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Inflamação/patologia , Doenças Inflamatórias Intestinais/terapia , Lactobacillus/fisiologia , Camundongos , Probióticos/farmacologia , Probióticos/uso terapêutico
10.
Free Radic Biol Med ; 188: 298-311, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35752373

RESUMO

The enzyme NADPH oxidase 1 (NOX1) is a major producer of superoxide which together with other reactive oxygen and nitrogen species (ROS/RNS) are implicated in maintaining a healthy epithelial barrier in the gut. While previous studies have indicated NOX1's involvement in microbial modulation in the small intestine, less is known about the effects of NOX1-dependent ROS/RNS formation in the colon. We investigated the role of NOX1 in the colon of NOX1 knockout (KO) and wild type (WT) mice, under mild and subclinical low-grade colon inflammation induced by 1% dextran sulfate sodium (DSS). Ex vivo imaging of ROS/RNS in the colon revealed that absence of NOX1 strongly decreased ROS/RNS production, particularly during DSS treatment. Furthermore, while absence of NOX1 did not affect disease activity, some markers of inflammation (mRNA: Tnfa, Il6, Ptgs2; protein: lipocalin 2) in the colonic mucosa tended to be higher in NOX1 KO than in WT mice following DSS treatment. Lack of NOX1 also extensively modulated the bacterial community in the colon (16S rRNA gene sequencing), where NOX1 KO mice were characterized mainly by lower α-diversity (richness and evenness), higher abundance of Firmicutes, Akkermansia, and Oscillibacter, and lower abundance of Bacteroidetes and Alistipes. Together, our data suggest that NOX1 is pivotal for colonic ROS/RNS production in mice both during steady-state (i.e., no DSS treatment) and during 1% DSS-induced low-grade inflammation and for modulation of the colonic microbiota, with potential beneficial consequences for intestinal health.


Assuntos
Colite , Microbiota , NADPH Oxidase 1 , Animais , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Colo/microbiologia , Sulfato de Dextrana/toxicidade , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NADPH Oxidase 1/genética , NADPH Oxidase 1/metabolismo , NADPH Oxidases/genética , RNA Ribossômico 16S/genética , Espécies Reativas de Oxigênio/farmacologia
11.
Microbiol Spectr ; 10(3): e0212421, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35658572

RESUMO

Limosilactobacillus reuteri plays an important role in regulating intestinal functions and maintaining barrier integrity in animals. In this study, Limosilactobacillus reuteri strain SLZX19-12 was isolated from the fecal microbiota of Tibetan pigs, and it was found that this strain is sensitive to common antibiotics and has strong resistance to stress. Upon being administered by gavage at different doses, including low, medium, and high doses, for 14 days, Limosilactobacillus reuteri SLZX19-12 may enhance the intestinal barrier. After administration of a high dose of SLZX19-12, mice were challenged with Salmonella enterica serovar Typhimurium SL1344. Infection with Salmonella Typhimurium SL1344 led to disordered colonic microbiotas, colonic inflammation through the S100A8/S100A9-NF-κB pathway and potential apoptosis, and translocation of pathogens to parenteral visceral organs in mice. However, the mice pretreated with Limosilactobacillus reuteri SLZX19-12 showed lower loads of Salmonella in visceral organs, less colonic inflammation, and higher barrier integrity. More importantly, the administration of strain SLZX19-12 resulted in a more stable microbiota structure of the colon, in which the abundance of Alloprevotella was greatly enhanced. Therefore, this study suggests that Limosilactobacillus reuteri SLZX19-12 can protect the colon from infection by enhancing the stability of gut microbiota and barrier integrity and reducing inflammation. IMPORTANCE The use of antibiotics to treat bacterial infections leads to a series of side effects. As an alternative method, the biocontrol strategy, which uses probiotics to suppress pathogens, is considered a potential way to deal with bacterial infections in gut. However, there are few probiotics that are currently safe and can protect against infection. In this study, Limosilactobacillus reuteri strain SLZX19-12 was obtained from Tibetan pigs, which have higher resistance to infection. This strain is sensitive to conventional antibiotics, secretes a wide spectrum of enzymes, and also promotes the intestinal barrier function in mice. In addition, Limosilactobacillus reuteri SLZX19-12 can promote the stability of the gut microbiota to avoid or alleviate the occurrence or development of foodborne infections.


Assuntos
Microbioma Gastrointestinal , Probióticos , Animais , Antibacterianos/farmacologia , Colo/microbiologia , Inflamação , Camundongos , Probióticos/uso terapêutico , Salmonella typhimurium , Suínos
12.
Food Res Int ; 156: 111156, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35651022

RESUMO

Until now, although different studies have shown the potential prebiotic effect of seaweed carbohydrates, no studies with the whole seaweeds have been carried out. In addition, the prebiotic effect throughput sequencing remains poorly investigated since most of the published works used qPCR or FISH to estimate bacterial changes. In this work, an in vitro model of the human distal colon was used to determine, for the first time, the potential prebiotic effect of a brown whole seaweed Himanthalia elongata. The whole seaweed was characterized in basis of its nutritional and mineral composition and submitted to the entire gastrointestinal digestion. The prebiotic effect was evaluated by the microbial modulation through 16S rRNA amplicon sequencing, qPCR and short-chain fatty acid analysis. The obtained results indicated that the colonic fraction of H. elongata was used selectively by the Bacteroides genus, more specifically by the specie Bacteoides ovatus, whereas inulin was used mainly by the Parabacteroides genus, being Parabacteroides distasonis the most abundant identified specie. Selective use of inulin by P. distasonis is, therefore, reported by the first time. qPCR analysis shown no significative differences in Bifidobacterium population and a decrease in Lactobacillus along the fermentation assays with both substrates. Regarding to the short-fatty acid production, maximal concentration, 56.11 ± 20.48 mM, was achieved for H. elongata, at 24 h of fermentation whereas for inulin total acid production was 93.66 ± 21.82 mM at 48 h of assay. The metabolic pathways associated with bacterial genera were not significantly different between the two tested substrates. Although more studies are necessary to elucidate the prebiotic character of H. elongata, the results presented in this work are promissory and could open new opportunities of research and application in the area of Nutrition and Food Chemistry.


Assuntos
Besouros , Feófitas , Alga Marinha , Animais , Colo/microbiologia , Humanos , Inulina , Feófitas/química , Prebióticos , RNA Ribossômico 16S/genética , Verduras
13.
J Appl Microbiol ; 133(3): 2063-2073, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35737740

RESUMO

AIMS: This study aimed to investigate the protective effect of Bifidobacterium animalis subsp. lactis A6 on dextran sodium sulphate (DSS)-induced colitis in C57BL/6J mice. METHODS AND RESULTS: Mice were randomly divided into three groups (n = 8 per group). Each group was administered with PBS (Control and DSS group) or B. lactis A6 with a dosage of ~4.0 × 109  CFU day-1 (DSS + A6 group) for 21 consecutive days. The DSS and DSS + A6 group mice were ad libitum drinking 2.5% DSS water during day 15-21, while the Control group mice were given normal water. The administration of B. lactis A6 significantly inhibited DSS-induced bodyweight loss and colon shortening (p < 0.001), but showed no significant influence on the spleen enlargement (p > 0.05). The intestinal barrier integrity was improved by reducing colonic damage, recovering mucus layer loss and enhancing tight junction expression including ZO-1, occludin and claudin-1. In addition, B. lactis A6 attenuated the oxidative stress by decreasing MDA and increasing SOD and GSH levels in colon tissues. Moreover, B. lactis A6 suppressed DSS-induced inflammatory responses via downregulating TNF-α, IL-1ß and IL-6 levels and upregulating IL-10 level in colon tissues. CONCLUSION: B. lactis A6 effectively alleviated DSS-induced colitis by maintaining intestinal barrier integrity, reducing oxidative stress and inhibiting inflammatory responses. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that B. lactis A6 could act as a candidate probiotic for UC treatment.


Assuntos
Anti-Inflamatórios , Bifidobacterium animalis , Colite , Animais , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/microbiologia , Sulfato de Dextrana/efeitos adversos , Sulfato de Dextrana/metabolismo , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Água/metabolismo
14.
Nutrients ; 14(9)2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35565775

RESUMO

Harboring various proteins, lipids, and RNAs, the extracellular vesicles (EVs) in milk exert vital tissue-specific immune-protective functions in neonates via these bioactive cargos. This study aims to explore the anti-inflammatory effects of bovine milk-derived EVs on a dextran sulfate sodium (DSS)-induced colitis model and to determine the underlying molecular mechanisms. Sixty C57BL/6 mice were divided into the NC group (normal control), DSS group (DSS + PBS), DSS + LOW group (DSS + 1.5 × 108 p/g EVs), DSS + MID group (DSS + 1.5 × 109 p/g EVs), and DSS + HIG group (DSS + 1.0 × 1010 p/g EVs). Histopathological sections, the gut microbiota, and intestinal tissue RNA-Seq were used to comprehensively evaluate the beneficial functions in mitigating colitis. The morphology exhibited that the milk-derived EVs contributed to the integrity of the superficial epithelial structure in the intestine. Additionally, the concentrations of IL-6 and TNF-α in the colon tissues were significantly decreased in the EVs-treated mice. The abundances of the Dubosiella, Bifidobacterium, UCG-007, Lachnoclostridium, and Lachnospiraceae genera were increased in the gut after treatment with the milk-derived EVs. Additionally, the butyrate and acetate production were enriched in feces. In addition, 1659 genes were significantly down-regulated and 1981 genes were significantly up-regulated in the EVs-treated group. Meanwhile, 82 lncRNAs and 6 circRNAs were also differentially expressed. Overall, the milk-derived EVs could attenuate colitis through optimizing gut microbiota abundance and by manipulating intestinal gene expression, implying their application potential for colitis prevention.


Assuntos
Colite , Vesículas Extracelulares , Microbioma Gastrointestinal , Animais , Colite/microbiologia , Colo/microbiologia , Sulfato de Dextrana/efeitos adversos , Suplementos Nutricionais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Leite , Transcriptoma
15.
FEMS Microbiol Ecol ; 98(5)2022 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-35511201

RESUMO

The primary objective of this study was to investigate if common colonic community indicators could be identified from the microbiota of 22-day-old suckling pigs in repeated small-scale trials. A total of three separate trials were conducted at different times in the same year and facility with genetically similar animals. Colonic samples were collected from four pigs in each trial and the microbiome composition assessed by 16s rRNA gene sequencing. Pig weight, average daily gain (ADG), bacterial diversity, and abundance were not significantly different between repeated trials, except for a significant difference in Jaccard Similarity. At genus level, the most abundant taxa identified were Porphyromonadaceae unclassified (15.81%), Ruminococcaceae unclassified, (12.78%), Prevotella (7.26%), Clostridiales unclassified (6.99%), Lactobacillus (6.58%), Phascolarctobacterium (6.52%), and Firmicutes unclassified (5.69%). The secondary objective was to establish if pooled data in terms of microbial diversity and abundance of the colonic microbiota related to weight and ADG. Pig weight at day 22 and ADG positively correlated with α-diversity. Abundance of potential protein digesting and short-chain fatty acid producing operational taxonomic units ascribed to Terrisporobacter, Ruminococcaceae unclassified, Intestinimonas, and Dorea correlated with weight and ADG, suggesting a nutritional role for these common colonic community microbiota members in suckling pigs.


Assuntos
Microbioma Gastrointestinal , Microbiota , Animais , Clostridiales/genética , Colo/microbiologia , Microbioma Gastrointestinal/genética , Prevotella , RNA Ribossômico 16S/genética , Suínos
16.
Microbiol Spectr ; 10(3): e0105522, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35587635

RESUMO

Enterotoxigenic Bacteroides fragilis (ETBF) is consistently found at higher frequency in individuals with sporadic and hereditary colorectal cancer (CRC) and induces tumorigenesis in several mouse models of CRC. However, whether specific mutations induced by ETBF lead to colon tumor formation has not been investigated. To determine if ETBF-induced mutations impact the Apc gene, and other tumor suppressors or proto-oncogenes, we performed whole-exome sequencing and whole-genome sequencing on tumors isolated after ETBF and sham colonization of Apcmin/+ and Apcmin/+Msh2fl/flVC mice, as well as whole-genome sequencing of organoids cocultured with ETBF. Our results indicate that ETBF-induced tumor formation results from loss of heterozygosity (LOH) of Apc, unless the mismatch repair system is disrupted, in which case, tumor formation results from new acquisition of protein-truncating mutations in Apc. In contrast to polyketide synthase-positive Escherichia coli (pks+ E. coli), ETBF does not produce a unique mutational signature; instead, ETBF-induced tumors arise from errors in DNA mismatch repair and homologous recombination DNA damage repair, established pathways of tumor formation in the colon, and the same genetic mechanism accounting for sham tumors in these mouse models. Our analysis informs how this procarcinogenic bacterium may promote tumor formation in individuals with inherited predispositions to CRC, such as Lynch syndrome or familial adenomatous polyposis (FAP). IMPORTANCE Many studies have shown that microbiome composition in both the mucosa and the stool differs in individuals with sporadic and hereditary colorectal cancer (CRC). Both human and mouse models have established a strong association between particular microbes and colon tumor induction. However, the genetic mechanisms underlying putative microbe-induced colon tumor formation are not well established. In this paper, we applied whole-exome sequencing and whole-genome sequencing to investigate the impact of ETBF-induced genetic changes on tumor formation. Additionally, we performed whole-genome sequencing of human colon organoids exposed to ETBF to validate the mutational patterns seen in our mouse models and begin to understand their relevance in human colon epithelial cells. The results of this study highlight the importance of ETBF colonization in the development of sporadic CRC and in individuals with hereditary tumor conditions, such as Lynch syndrome and familial adenomatous polyposis (FAP).


Assuntos
Polipose Adenomatosa do Colo , Infecções Bacterianas , Neoplasias do Colo , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Animais , Infecções Bacterianas/patologia , Bacteroides fragilis/genética , Bacteroides fragilis/metabolismo , Colo/microbiologia , Neoplasias do Colo/genética , Neoplasias do Colo/microbiologia , Neoplasias do Colo/patologia , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Modelos Animais de Doenças , Escherichia coli/genética , Genes APC , Camundongos , Mutação
17.
NPJ Biofilms Microbiomes ; 8(1): 21, 2022 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-35395818

RESUMO

Knowledge of the functional roles and interspecies interactions are crucial for improving our understanding of the human intestinal microbiome in health and disease. However, the complexity of the human intestinal microbiome and technical challenges in investigating it pose major challenges. In this proof-of-concept study, we rationally designed, assembled and experimentally tested a synthetic Diet-based Minimal Microbiome (Db-MM) consisting of ten core intestinal bacterial species that together are capable of efficiently converting dietary fibres into short chain fatty acids (SCFAs). Despite their genomic potential for metabolic competition, all ten bacteria coexisted during growth on a mixture of dietary fibres, including pectin, inulin, xylan, cellobiose and starch. By integrated analyses of metabolite production, community composition and metatranscriptomics-based gene expression data, we identified interspecies metabolic interactions leading to production of key SCFAs such as butyrate and propionate. While public goods, such as sugars liberated from colonic fibres, are harvested by non-degraders, some species thrive by cross-feeding on energetically challenging substrates, including the butyrogenic conversion of acetate and lactate. Using a reductionist approach in an in-vitro system combined with functional measurements, our study provides key insights into the complex interspecies metabolic interactions between core intestinal bacterial species.


Assuntos
Microbioma Gastrointestinal , Bactérias/genética , Bactérias/metabolismo , Colo/microbiologia , Fibras na Dieta , Ácidos Graxos Voláteis , Humanos
18.
Microbiol Spectr ; 10(3): e0269221, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35438531

RESUMO

Early-life gastrointestinal microbiota development is crucial for physiological development and immunological homeostasis. In the current study, perinatal microbiota and the development of gastrointestinal microbiota in different early-life periods (perinatal, lactation, and postweaning nutrition periods) were explored by using an antibiotic-interfered mouse model and a dextran sulfate sodium-induced colitis mouse model. Gut microbiota samples were collected from mother mice and litters. The results of 16S rRNA gene sequences suggested that microbiota in the gastrointestinal system were present in prenatal fetal mice, and microbiota structures in different parts of the gastrointestinal system of the fetal mice were similar to those in the corresponding gut parts of maternal mice. Microbiota in mucus samples from different regions exhibited higher diversity at birth than at other periods and varied substantially over time with diet change. Moreover, antibiotic treatment in early life affected the composition and diversity of gastrointestinal microbiota in adult mice and enhanced susceptibility to experimental colitis in mice, particularly in the lactation period. This approach of exploring gut microbiota evolution is hoped to provide an enhanced view of how resident microbiota develop in early life, which in turn might facilitate understanding of gut microbiota and related diseases. IMPORTANCE This study investigated resident microbiota in the whole gastrointestinal (GI) tract to explore gut microbiota development in early life and found that early-life antibiotic exposure exacerbated alterations in gut microbiota and murine dextran sulfate sodium (DSS)-induced colitis. Furthermore, the presence of bacteria in the GI tract of mice before birth and the importance of the lactation period in GI microbiota development were confirmed.


Assuntos
Colite , Microbioma Gastrointestinal , Animais , Antibacterianos/efeitos adversos , Colite/induzido quimicamente , Colite/microbiologia , Colo/microbiologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Feminino , Microbioma Gastrointestinal/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , RNA Ribossômico 16S/genética
19.
J Sci Food Agric ; 102(13): 5913-5924, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35437780

RESUMO

BACKGROUND: This study aimed to evaluate the effects of sub-therapeutic antibiotic (STA) administration and its subsequent withdrawal on the body tissue deposition, gut microbiota, and metabolite profiles of piglets. The piglets in the experimental group were fed with STA (30 mg kg-1 bacitracin methylene disalicylate, 75 mg kg-1 chlortetracycline, 300 mg kg-1 calcium oxytetracycline) for 14 days and the target bodyweight of the withdrawal period was 25 kg. RESULTS: The experiment was divided into two periods: the administration period and the withdrawal period. The results showed that STA did not improve piglets' growth performance during the two periods. Piglets treated with STA had lower body water deposition during the withdrawal period and tended to increase body lipid deposition during the withdrawal period and the whole period in comparison with the piglets in the control group. It was found that STA markedly altered the colonic microbiota and their metabolites in the piglets. Sub-therapeutic antibiotics were initially effective in decreasing the abundance of pathogenic bacteria during the administration period; however, STA could not continue the effect during the withdrawal period, leading to a rebound of pathogenic bacteria such as Alloprevotella and the increased abundance of other pathogenic bacteria like Oscillibacter. Remarkably, STA treatment decreased Blautia abundance. This bacterium plays a potential protective role against obesity. Metabolomic analysis indicated that STA mainly altered amino acid metabolism, lipid metabolism, and carbohydrate metabolism during the two periods. Spearman's correlation analysis showed that the gut microbiota was highly correlated with microbial metabolite changes. CONCLUSION: These results suggest that early STA administration may alter body tissue deposition later in life by reshaping the gut microbiota and their metabolite profiles. © 2022 Society of Chemical Industry.


Assuntos
Microbioma Gastrointestinal , Animais , Antibacterianos/farmacologia , Bactérias/genética , Colo/microbiologia , Suínos , Desmame
20.
Gut Microbes ; 14(1): 2041342, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35239459

RESUMO

The immune system in the large intestine is separated from commensal microbes and comparatively rare enteric pathogens by a monolayer of diverse epithelial cells overlaid with a compact and adherent inner mucus layer and a looser outer mucus layer. Microorganisms, collectively referred to as the mucus-associated (MA) microbiota, physically inhabit this mucus barrier, resulting in a dynamic and incessant dialog to maintain both spatial segregation and immune tolerance. Recent major findings reveal novel features of the crosstalk between the immune system and mucus-associated bacteria in health and disease, as well as disease-related peripheral immune signatures indicative of host responses to these organisms. In this brief review, we integrate these novel observations into our overall understanding of host-microbiota mutualism at the colonic mucosal border and speculate on the significance of this emerging knowledge for our understanding of the prevention, development, and progression of chronic intestinal inflammation.


Assuntos
Microbioma Gastrointestinal , Simbiose , Colo/microbiologia , Humanos , Sistema Imunitário , Inflamação , Mucosa Intestinal/microbiologia , Muco/microbiologia
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