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1.
FASEB J ; 38(11): e23648, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38822661

RESUMO

Previous studies on germ-free (GF) animals have described altered anxiety-like and social behaviors together with dysregulations in brain serotonin (5-HT) metabolism. Alterations in circulating 5-HT levels and gut 5-HT metabolism have also been reported in GF mice. In this study, we conducted an integrative analysis of various behaviors as well as markers of 5-HT metabolism in the brain and along the GI tract of GF male mice compared with conventional (CV) ones. We found a strong decrease in locomotor activity, accompanied by some signs of increased anxiety-like behavior in GF mice compared with CV mice. Brain gene expression analysis showed no differences in HTR1A and TPH2 genes. In the gut, we found decreased TPH1 expression in the colon of GF mice, while it was increased in the cecum. HTR1A expression was dramatically decreased in the colon, while HTR4 expression was increased both in the cecum and colon of GF mice compared with CV mice. Finally, SLC6A4 expression was increased in the ileum and colon of GF mice compared with CV mice. Our results add to the evidence that the microbiota is involved in regulation of behavior, although heterogeneity among studies suggests a strong impact of genetic and environmental factors on this microbiota-mediated regulation. While no impact of GF status on brain 5-HT was observed, substantial differences in gut 5-HT metabolism were noted, with tissue-dependent results indicating a varying role of microbiota along the GI tract.


Assuntos
Comportamento Animal , Vida Livre de Germes , Serotonina , Animais , Serotonina/metabolismo , Camundongos , Masculino , Microbioma Gastrointestinal/fisiologia , Encéfalo/metabolismo , Triptofano Hidroxilase/metabolismo , Triptofano Hidroxilase/genética , Ansiedade/metabolismo , Ansiedade/microbiologia , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Camundongos Endogâmicos C57BL , Receptor 5-HT1A de Serotonina/metabolismo , Receptor 5-HT1A de Serotonina/genética , Colo/metabolismo , Colo/microbiologia
2.
Gut Microbes ; 16(1): 2359500, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38825783

RESUMO

The gut microbiota has been implicated as a driver of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Recently we described, mucosal biofilms, signifying alterations in microbiota composition and bile acid (BA) metabolism in IBS and ulcerative colitis (UC). Luminal oxygen concentration is a key factor in the gastrointestinal (GI) ecosystem and might be increased in IBS and UC. Here we analyzed the role of archaea as a marker for hypoxia in mucosal biofilms and GI homeostasis. The effects of archaea on microbiome composition and metabolites were analyzed via amplicon sequencing and untargeted metabolomics in 154 stool samples of IBS-, UC-patients and controls. Mucosal biofilms were collected in a subset of patients and examined for their bacterial, fungal and archaeal composition. Absence of archaea, specifically Methanobrevibacter, correlated with disrupted GI homeostasis including decreased microbial diversity, overgrowth of facultative anaerobes and conjugated secondary BA. IBS-D/-M was associated with absence of archaea. Presence of Methanobrevibacter correlated with Oscillospiraceae and epithelial short chain fatty acid metabolism and decreased levels of Ruminococcus gnavus. Absence of fecal Methanobrevibacter may indicate a less hypoxic GI environment, reduced fatty acid oxidation, overgrowth of facultative anaerobes and disrupted BA deconjugation. Archaea and Ruminococcus gnavus could distinguish distinct subtypes of mucosal biofilms. Further research on the connection between archaea, mucosal biofilms and small intestinal bacterial overgrowth should be performed.


Assuntos
Archaea , Bactérias , Biofilmes , Fezes , Microbioma Gastrointestinal , Humanos , Biofilmes/crescimento & desenvolvimento , Archaea/classificação , Archaea/metabolismo , Archaea/genética , Archaea/isolamento & purificação , Adulto , Pessoa de Meia-Idade , Feminino , Masculino , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Bactérias/isolamento & purificação , Fezes/microbiologia , Colo/microbiologia , Methanobrevibacter/metabolismo , Methanobrevibacter/genética , Methanobrevibacter/crescimento & desenvolvimento , Methanobrevibacter/isolamento & purificação , Colite Ulcerativa/microbiologia , Colite Ulcerativa/metabolismo , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/metabolismo , Idoso , Mucosa Intestinal/microbiologia , Mucosa Intestinal/metabolismo , Íleo/microbiologia , Ácidos Graxos Voláteis/metabolismo , Adulto Jovem , Ácidos e Sais Biliares/metabolismo
3.
J Agric Food Chem ; 72(23): 13415-13430, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38824655

RESUMO

This study aimed to investigate the hypothesis that dietary konjac glucomannan (KGM) could alleviate Salmonella typhimurium-induced colitis by modulating intestinal microbiota. Mice were fed an isocaloric and isofibrous diet supplemented with either 7% KGM or cellulose and were treated with 5 × 108 CFU of S. typhimurium. The results showed that KGM had an average molecular weight of 936 kDa and predominantly consisted of mannose and glucose at a molar ratio of 1:1.22. In vivo studies demonstrated that dietary KGM effectively mitigated colonic lesions, oxidative stress, disruption of tight junction protein 2 and occludin, and the inflammatory response induced by S. typhimurium. Moreover, KGM administration alleviated the dramatic upregulation of toll-like receptor 2 (TLR2) and phosphonuclear factor κB (NF-κB) protein abundance, induced by Salmonella treatment. Notably, dietary KGM restored the reduced Muribaculaceae and Lactobacillus abundance and increased the abundance of Blautia and Salmonella in S. typhimurium-infected mice. Spearman correlation analysis revealed that the gut microbiota improved by KGM contribute to inhibit inflammation and oxidative stress. These results demonstrated the protective effects of dietary KGM against colitis by modulating the gut microbiota and the TLR2-NF-κB signaling pathway in response to Salmonella infection.


Assuntos
Colite , Colo , Microbioma Gastrointestinal , Mananas , NF-kappa B , Salmonella typhimurium , Transdução de Sinais , Receptor 2 Toll-Like , Animais , Mananas/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Receptor 2 Toll-Like/metabolismo , Receptor 2 Toll-Like/genética , NF-kappa B/metabolismo , NF-kappa B/genética , Colo/microbiologia , Colo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Colite/induzido quimicamente , Colite/metabolismo , Colite/microbiologia , Colite/dietoterapia , Masculino , Humanos , Camundongos Endogâmicos C57BL , Fibras na Dieta/farmacologia , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/metabolismo , Bactérias/efeitos dos fármacos , Amorphophallus/química
4.
Int J Biol Macromol ; 272(Pt 1): 132906, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38851991

RESUMO

Sourdough bread enriched with soluble fiber (by in-situ exopolysaccharides production) and insoluble fiber (by gazpacho by-products addition) showed prebiotic effects an in vitro dynamic colonic fermentation performance with obese volunteer's microbiota. Bifidobacterium population was maintained whereas Lactobacillus increased throughout the colonic sections. Conversely, Enterobacteriaceae and Clostridium groups clearly decreased. Specific bacteria associated with beneficial effects increased in the ascending colon (Lactobacillus fermentum, Lactobacillus paracasei, Bifidobacterium longum and Bifidobacterium adolescentis) whereas Eubacterium eligens, Alistipes senegalensis, Prevotella copri and Eubacterium desmolans increased in the transversal and descending colon. Additionally, Blautia faecis and Ruminococcus albus increased in the transversal colon, and Bifidobacterium longum, Roseburia faecis and Victivallis vadensis in the descending colon. Bifidobacterium and Lactobacillus fermented the in-situ exopolysaccharides and released pectins from gazpacho by-products, as well as cellulosic degraded bacteria. This increased the short and medium chain fatty acids. Acetic acid, as well as butyric acid, increased throughout the colonic tract, which showed greater increases only in the transversal and descending colonic segments. Conversely, propionic acid was slightly affected by the colonic fermentation. These results show that sourdough bread is a useful food matrix for the enrichment of vegetable by-products (or other fibers) in order to formulate products with microbiota modulatory capacities.


Assuntos
Pão , Disbiose , Fermentação , Pão/microbiologia , Humanos , Disbiose/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Fibras na Dieta/metabolismo , Polissacarídeos Bacterianos/farmacologia , Colo/microbiologia , Colo/metabolismo , Bifidobacterium/metabolismo , Masculino , Lactobacillus/metabolismo
5.
Food Funct ; 15(12): 6717-6730, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38833212

RESUMO

Although only Saccharomyces boulardii has been studied for ulcerative colitis (UC), probiotic yeasts have immense therapeutic potential. Herein, we evaluated the kefir yeast Kluyveromyces marxianus A4 (Km A4) and its anti-inflammatory effect with sulfasalazine in BALB/c mice with dextran sulfate sodium (DSS)-induced colitis. Oral administration continued for 7 days after the mice were randomly divided into seven groups: control (CON, normal mice administered with saline), DSS-induced colitis mice administered saline (DSS), and DSS-induced colitis mice administered sulfasalazine only (S), Km A4 only (A4), Km A4 plus sulfasalazine (A4 + S), S. boulardii ATCC MYA-796 (Sb MYA-796) only (Sb), and Sb MYA-796 plus sulfasalazine (Sb + S). The ß-glucan content of Km A4 was significantly higher than that of Sb MYA-796 (P < 0.05). Body weight gain (BWG) significantly correlated with colon length, cyclooxygenase-2 (Cox-2) levels, and Bacteroides abundance (P < 0.05). In colitis-induced mice, the A4 + S group had the lowest histological score (6.00) compared to the DSS group (12.67), indicating the anti-inflammatory effects of this combination. The A4 + S group showed significantly downregulated expression of interleukin (Il)-6, tumor necrosis factor-α (Tnf-α), and Cox-2 and upregulated expression of Il-10 and occludin (Ocln) compared to the DSS group. Mice treated with A4 + S had enhanced Bacteroides abundance in their gut microbiota compared with the DSS group (P < 0.05). Bacteroides were significantly correlated with all colitis biomarkers (BWG, colon length, Il-6, Tnf-α, Il-10, Cox-2, and Ocln; P < 0.05). The anti-inflammatory effects of Km A4 could be attributed to high ß-glucan content and gut microbiota modulation. Thus, treatment with Km A4 and sulfasalazine could alleviate UC.


Assuntos
Anti-Inflamatórios , Colite Ulcerativa , Microbioma Gastrointestinal , Kluyveromyces , Camundongos Endogâmicos BALB C , Probióticos , Sulfassalazina , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/microbiologia , Colite Ulcerativa/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Sulfassalazina/farmacologia , Camundongos , Anti-Inflamatórios/farmacologia , Probióticos/farmacologia , Masculino , Kefir/microbiologia , Sulfato de Dextrana/efeitos adversos , Humanos , Colo/microbiologia , Colo/metabolismo , Colo/efeitos dos fármacos , Colo/patologia , Modelos Animais de Doenças , Feminino
6.
Int Immunopharmacol ; 134: 112234, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38739976

RESUMO

Ulcerative colitis, a chronic inflammatory condition affecting the rectum and colon to varying degrees, is linked to a dysregulated immune response and the microbiota. Sodium (aS,9R)-3-hydroxy-16,17-dimethoxy-15-oxidotricyclo[12.3.1.12,6]nonadeca-1(18),2,4,6(19),14,16-hexene-9-yl sulfate hydrate (SDH) emerges as a novel diarylheptane compound aimed at treating inflammatory bowel diseases. However, the mechanisms by which SDH modulates these conditions remain largely unknown. In this study, we assessed SDH's impact on the clinical progression of dextran sodium sulfate (DSS)-induced ulcerative colitis. Our results demonstrated that SDH significantly mitigated the symptoms of DSS-induced colitis, reflected in reduced disease activity index scores, alleviation of weight loss, shortening of the colorectum, and reduction in spleen swelling. Notably, SDH decreased the proportion of Th1/Th2/Th17 cells and normalized inflammatory cytokine levels in the colon. Furthermore, SDH treatment modified the gut microbial composition in mice with colitis, notably decreasing Bacteroidetes and Proteobacteria populations while substantially increasing Firmicutes, Actinobacteria, and Patescibacteria. In conclusion, our findings suggest that SDH may protect the colon from DSS-induced colitis through the regulation of Th1/Th2/Th17 cells and gut microbiota, offering novel insights into SDH's therapeutic potential.


Assuntos
Colite Ulcerativa , Sulfato de Dextrana , Diarileptanoides , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Diarileptanoides/farmacologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/imunologia , Colite Ulcerativa/microbiologia , Colo/efeitos dos fármacos , Colo/imunologia , Colo/patologia , Colo/microbiologia , Citocinas/metabolismo , Modelos Animais de Doenças , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/imunologia , Colite/microbiologia , Masculino , Células Th1/imunologia , Células Th1/efeitos dos fármacos , Células Th17/imunologia , Células Th17/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Células Th2/imunologia , Células Th2/efeitos dos fármacos , Humanos
7.
Molecules ; 29(9)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38731645

RESUMO

Ulcerative colitis (UC), as a chronic inflammatory disease, presents a global public health threat. However, the mechanism of Poria cocos (PC) in treating UC remains unclear. Here, LC-MS/MS was carried out to identify the components of PC. The protective effect of PC against UC was evaluated by disease activity index (DAI), colon length and histological analysis in dextran sulfate sodium (DSS)-induced UC mice. ELISA, qPCR, and Western blot tests were conducted to assess the inflammatory state. Western blotting and immunohistochemistry techniques were employed to evaluate the expression of tight junction proteins. The sequencing of 16S rRNA was utilized for the analysis of gut microbiota regulation. The results showed that a total of fifty-two nutrients and active components were identified in PC. After treatment, PC significantly alleviated UC-associated symptoms including body weight loss, shortened colon, an increase in DAI score, histopathologic lesions. PC also reduced the levels of inflammatory cytokines TNF-α, IL-6, and IL-1ß, as evidenced by the suppressed NF-κB pathway, restored the tight junction proteins ZO-1 and Claudin-1 in the colon, and promoted the diversity and abundance of beneficial gut microbiota. Collectively, these findings suggest that PC ameliorates colitis symptoms through the reduction in NF-κB signaling activation to mitigate inflammatory damage, thus repairing the intestinal barrier, and regulating the gut microbiota.


Assuntos
Colite Ulcerativa , Sulfato de Dextrana , Microbioma Gastrointestinal , NF-kappa B , Transdução de Sinais , Wolfiporia , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/microbiologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , NF-kappa B/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Wolfiporia/química , Masculino , Modelos Animais de Doenças , Citocinas/metabolismo , Colo/patologia , Colo/metabolismo , Colo/efeitos dos fármacos , Colo/microbiologia , Proteínas de Junções Íntimas/metabolismo , Camundongos Endogâmicos C57BL
8.
Int J Pharm ; 658: 124223, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38744413

RESUMO

This study aimed to microencapsulate the probiotic strain Lactiplantibacillus plantarum 4S6R (basonym Lactobacillus plantarum) in both microcapsules and microspheres by prilling/vibration technique. A specific polymeric mixture, selected for its responsiveness to parallel colonic stimuli, was individuated as a carrier of microparticles. Although the microspheres were consistent with some critical quality parameters, they showed a low encapsulation efficiency and were discarded. The microcapsules produced demonstrated high yields (97.52%) and encapsulation efficiencies (90.06%), with dimensional analysis and SEM studies confirming the desired size morphology and structure. The results of thermal stress tests indicate the ability of the microcapsules to protect the probiotic. Stability studies showed a significant advantage of the microcapsules over non-encapsulated probiotics, with greater stability over time. The release study under simulated gastrointestinal conditions demonstrated the ability of the microcapsules to protect the probiotics from gastric acid and bile salts, ensuring their viability. Examination in a simulated faecal medium revealed the ability of the microcapsules to release the bacteria into the colon, enhancing their beneficial impact on gut health. This research suggests that the selected mixture of reactive polymers holds promise for improving the survival and efficacy of probiotics in the gastrointestinal tract, paving the way for the development of advanced probiotic products.


Assuntos
Cápsulas , Colo , Lactobacillus plantarum , Microesferas , Probióticos , Probióticos/administração & dosagem , Colo/microbiologia , Colo/metabolismo , Ácidos e Sais Biliares/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Tamanho da Partícula , Sistemas de Liberação de Medicamentos/métodos , Ácido Gástrico/química , Ácido Gástrico/metabolismo , Estabilidade de Medicamentos , Fezes/microbiologia
9.
Gut Microbes ; 16(1): 2356270, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38797998

RESUMO

High-fat diets alter gut barrier integrity, leading to endotoxemia by impacting epithelial functions and inducing endoplasmic reticulum (ER) stress in intestinal secretory goblet cells. Indeed, ER stress, which is an important contributor to many chronic diseases such as obesity and obesity-related disorders, leads to altered synthesis and secretion of mucins that form the protective mucus barrier. In the present study, we investigated the relative contribution of omega-3 polyunsaturated fatty acid (PUFAs)-modified microbiota to alleviating alterations in intestinal mucus layer thickness and preserving gut barrier integrity. Male fat-1 transgenic mice (exhibiting endogenous omega-3 PUFAs tissue enrichment) and wild-type (WT) littermates were fed either an obesogenic high-fat diet (HFD) or a control diet. Unlike WT mice, HFD-fed fat-1 mice were protected against mucus layer alterations as well as an ER stress-mediated decrease in mucin expression. Moreover, cecal microbiota transferred from fat-1 to WT mice prevented changes in the colonic mucus layer mainly through colonic ER stress downregulation. These findings highlight a novel feature of the preventive effects of omega-3 fatty acids against intestinal permeability in obesity-related conditions.


Assuntos
Colo , Dieta Hiperlipídica , Estresse do Retículo Endoplasmático , Ácidos Graxos Ômega-3 , Microbioma Gastrointestinal , Mucosa Intestinal , Camundongos Transgênicos , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos , Masculino , Ácidos Graxos Ômega-3/metabolismo , Colo/microbiologia , Colo/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Obesidade/metabolismo , Obesidade/microbiologia , Muco/metabolismo , Camundongos Endogâmicos C57BL , Mucinas/metabolismo , Células Caliciformes/metabolismo , Transplante de Microbiota Fecal
10.
Food Funct ; 15(11): 5813-5824, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38747641

RESUMO

Carbohydrates are an important macronutrient whose processing and digestive fate can have numerous beneficial or adverse effects on consumer health. This study investigated the impact of heat-moisture treatments (HMT) and citric acid treatments (CAT) on arrowroot starch (ARS) with a focus on its physicochemical properties, digestibility, and influence on gut microbiota. The results revealed that HMT and CAT did not alter the colloidal characteristics of ARS but significantly affected the balance between amorphous and crystalline regions. Changes in thermal properties, morphology, and particle size were also observed. These can influence ARS shelf life and functional properties in various food applications. Furthermore, certain treatments in both processing methods increased the resistant starch (RS) content of ARS, with HMT for 16 hours at 80 °C and CAT with 0.6 M citric acid, resulting in the most pronounced effects. These changes coincided with reductions in rapidly digestible starch (RDS) levels and improvements in the ratio of slowly digestible starch (SDS) to RDS, which could potentially improve glycemic control. This study also examined the impact of processed ARS on colonic microbiota composition. It found that ARS-derived RS formed under HMT and CAT did not negatively affect the prebiotic potential of the RS fraction. Both treatments were associated with lowering the Firmicutes to Bacteroidetes ratio (F/B), a marker of gut health, and decreasing the relative abundance of Proteobacteria, microbes associated with adverse health effects. Additionally, CAT-derived RS showed a significant increase in the relative abundance of Roseburia, a beneficial gut bacterium. In conclusion, processing ARS through HMT and CAT techniques has the potential for enhancing its RS content, improving its glycemic impact, and positively influencing the gut microbiota composition, potentially contributing to gut health and metabolic well-being.


Assuntos
Colo , Microbioma Gastrointestinal , Temperatura Alta , Prebióticos , Amido , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Amido/química , Amido/metabolismo , Colo/microbiologia , Colo/metabolismo , Masculino , Ácido Cítrico/farmacologia , Amido Resistente/farmacologia , Bactérias/classificação , Bactérias/metabolismo , Digestão , Adulto , Feminino , Manipulação de Alimentos/métodos
11.
Mol Syst Biol ; 20(6): 596-625, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38745106

RESUMO

The erosion of the colonic mucus layer by a dietary fiber-deprived gut microbiota results in heightened susceptibility to an attaching and effacing pathogen, Citrobacter rodentium. Nevertheless, the questions of whether and how specific mucolytic bacteria aid in the increased pathogen susceptibility remain unexplored. Here, we leverage a functionally characterized, 14-member synthetic human microbiota in gnotobiotic mice to deduce which bacteria and functions are responsible for the pathogen susceptibility. Using strain dropouts of mucolytic bacteria from the community, we show that Akkermansia muciniphila renders the host more vulnerable to the mucosal pathogen during fiber deprivation. However, the presence of A. muciniphila reduces pathogen load on a fiber-sufficient diet, highlighting the context-dependent beneficial effects of this mucin specialist. The enhanced pathogen susceptibility is not owing to altered host immune or pathogen responses, but is driven by a combination of increased mucus penetrability and altered activities of A. muciniphila and other community members. Our study provides novel insights into the mechanisms of how discrete functional responses of the same mucolytic bacterium either resist or enhance enteric pathogen susceptibility.


Assuntos
Akkermansia , Citrobacter rodentium , Microbioma Gastrointestinal , Animais , Camundongos , Citrobacter rodentium/patogenicidade , Humanos , Suscetibilidade a Doenças , Fibras na Dieta/metabolismo , Vida Livre de Germes , Dieta , Mucosa Intestinal/microbiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/imunologia , Verrucomicrobia/genética , Infecções por Enterobacteriaceae/microbiologia , Colo/microbiologia , Camundongos Endogâmicos C57BL
12.
J Agric Food Chem ; 72(23): 13099-13110, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38807079

RESUMO

Whole-grain foods are rich in bound polyphenols (BPs) whose health benefits were largely underestimated compared with free polyphenols. We first found that DFBP (dietary fiber with BPs from oat bran) exhibited stronger colonic antioxidant activities than DF. 16S rRNA sequencing showed that DFBP selectively changed gut microbial composition, which reciprocally released BPs from DFBP. Released polyphenols from DFBP reduced excessive colonic ROS and exhibited colonic antioxidant activities via the ROS/Akt/Nrf2 pathway revealed by transcriptome and western blot analysis. Colonic antioxidant activities of DFBP mediated by gut microbiota were next proven by treating mice with broad-spectrum antibiotics. Next, Clostridium butyricum, as a distinguished bacterium after DFBP intervention, improved colonic antioxidant capacities synergistically with DFBP in HFD-fed mice. This was explained by the upregulated mRNA expression of esterase, and cellulase of Clostridium butyricum participated in releasing BPs. Our results would provide a solid basis for explaining the health benefits of whole grains.


Assuntos
Avena , Colo , Dieta Hiperlipídica , Fibras na Dieta , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Polifenóis , Proteínas Proto-Oncogênicas c-akt , Espécies Reativas de Oxigênio , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Camundongos , Polifenóis/farmacologia , Polifenóis/química , Polifenóis/administração & dosagem , Polifenóis/metabolismo , Avena/química , Avena/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fibras na Dieta/metabolismo , Fibras na Dieta/farmacologia , Masculino , Dieta Hiperlipídica/efeitos adversos , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Colo/metabolismo , Colo/microbiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Espécies Reativas de Oxigênio/metabolismo , Humanos , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Bactérias/efeitos dos fármacos
13.
Food Chem ; 453: 139630, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-38781895

RESUMO

Rutin is a polyphenol with beneficial pharmacological properties. However, its bioavailability is often compromised due to low solubility and poor stability. Encapsulation technologies, such as emulsion systems, have been proven to be promising delivery vehicles for enhancing the bioavailability of bioactive compounds. Thus, this study was proposed and designed to investigate the colonic targeting and colonic fermentation characteristics of rutin-loaded ovalbumin-ferulic acid-polysaccharide (OVA-FA-PS) complex emulsions. The results indicate that OVA-FA-PS emulsion effectively inhibits the degradation of rutin active substances and facilitates its transport of rutin to the colon. The analysis revealed that the OVA-FA-κ-carrageenan emulsion loaded with rutin exhibited superior elasticity and colon targeting properties compared to the OVA-FA-hyaluronic acid or OVA-FA-sodium alginate emulsions loaded with rutin in the composite emulsion. Additionally, it was observed that the rutin loaded within the OVA-FA-κ-carrageenan emulsion underwent degradation and was converted to 4-hydroxybenzoic acid during colonic fermentation.


Assuntos
Colo , Ácidos Cumáricos , Emulsões , Fermentação , Ovalbumina , Polissacarídeos , Colo/metabolismo , Colo/microbiologia , Emulsões/química , Emulsões/metabolismo , Ovalbumina/química , Ovalbumina/metabolismo , Ácidos Cumáricos/química , Ácidos Cumáricos/metabolismo , Polissacarídeos/química , Polissacarídeos/metabolismo , Animais , Rutina/química , Rutina/metabolismo , Masculino
14.
BMC Microbiol ; 24(1): 156, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724913

RESUMO

BACKGROUND: To establish a method to induce Campylobacter jejuni colonization in the intestines of C57BL/6 mice through antibiotic-induced microbiome depletion. RESULTS: Fifty-four female C57BL/6 mice were divided into the normal, control, and experimental groups. The experimental group was administered intragastric cefoperazone sodium and sulbactam sodium (50 mg/mL) for 2 days; then, the experimental and control mice were intragastrically administered 200 µL C. jejuni, which was repeated once more after 2 days. Animal feces were collected, and the HipO gene of C. jejuni was detected using TaqMan qPCR from day 1 to day 14 after modeling completion. Immunofluorescence was used to detect intestinal C. jejuni colonization on day 14, and pathological changes were observed using hematoxylin and eosin staining. Additionally, 16S rDNA analyses of the intestinal contents were conducted on day 14. In the experimental group, C. jejuni was detected in the feces from days 1 to 14 on TaqMan qPCR, and immunofluorescence-labeled C. jejuni were visibly discernable in the intestinal lumen. The intestinal mucosa was generally intact and showed no significant inflammatory-cell infiltration. Diversity analysis of the colonic microbiota showed significant inter-group differences. In the experimental group, the composition of the colonic microbiota differed from that in the other 2 groups at the phylum level, and was characterized by a higher proportion of Bacteroidetes and a lower proportion of Firmicutes. CONCLUSIONS: Microbiome depletion induced by cefoperazone sodium and sulbactam sodium could promote long-term colonization of C. jejuni in the intestines of mice.


Assuntos
Antibacterianos , Infecções por Campylobacter , Campylobacter jejuni , Cefoperazona , Fezes , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S , Sulbactam , Animais , Campylobacter jejuni/efeitos dos fármacos , Campylobacter jejuni/crescimento & desenvolvimento , Feminino , Antibacterianos/farmacologia , Cefoperazona/farmacologia , Fezes/microbiologia , Infecções por Campylobacter/microbiologia , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Sulbactam/farmacologia , RNA Ribossômico 16S/genética , Intestinos/microbiologia , Colo/microbiologia , Colo/patologia , Modelos Animais de Doenças , Mucosa Intestinal/microbiologia , Mucosa Intestinal/efeitos dos fármacos , DNA Bacteriano/genética , DNA Ribossômico/genética
15.
Am J Physiol Gastrointest Liver Physiol ; 327(1): G36-G46, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38713615

RESUMO

Humans and mammals obtain vitamin B1 from dietary and gut microbiota sources. A considerable amount of the microbiota-generated vitamin exists in the form of thiamine pyrophosphate (TPP), and colonocytes are capable of absorbing TPP via a specific carrier-mediated process that involves the colonic TPP transporter (cTPPT encoded by SLC44A4). Little is known about the relative contribution of the SLC44A4 transporter toward total colonic carrier-mediated TPP uptake and its role in colon physiology. To address these issues, we generated an Slc44a4 knockout (KO) mouse model (by Cre-Lox recombination) and found a near-complete inhibition in colonic carrier-mediated [3H]TPP uptake in the Slc44a4 KO compared with wild-type (WT) littermates. We also observed a significant reduction in KO mice's body weight and a shortening of their colon compared with WT. Using RNAseq and Ingenuity pathway analysis (IPA) approaches, we found that knocking out the colonic Slc44a4 led to changes in the level of expression of many genes, including upregulation in those associated with intestinal inflammation and colitis. Finally, we found that the Slc44a4 KO mice were more susceptible to the effect of the colitogenic dextran sodium sulfate (DSS) compared with WT animals, a finding that lends support to the recent prediction by multiple genome-wide association studies (GWAS) that SLC44A4 is a possible colitis susceptibility gene. In summary, the results of these investigations show that Slc44a4 is the predominant or only transporter involved in the colonic uptake of TPP, that the transporter is important for colon physiology, and that its deletion increases susceptibility to inflammation.NEW & NOTEWORTHY This study shows that Slc44a4 is the predominant or only transport system involved in the uptake of the gut microbiota-generated thiamine pyrophosphate (TPP) in the colon and that its deletion affects colon physiology and increases its susceptibility to inflammation.


Assuntos
Colo , Microbioma Gastrointestinal , Camundongos Knockout , Tiamina Pirofosfato , Animais , Humanos , Masculino , Camundongos , Transporte Biológico , Colite/metabolismo , Colite/microbiologia , Colite/genética , Colite/induzido quimicamente , Colo/metabolismo , Colo/microbiologia , Microbioma Gastrointestinal/fisiologia , Absorção Intestinal , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/genética , Camundongos Endogâmicos C57BL , Tiamina Pirofosfato/metabolismo
16.
Cell Host Microbe ; 32(6): 1025-1036.e5, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38795710

RESUMO

The extent to which bacterial lipids produced by the gut microbiota penetrate host tissues is unclear. Here, we combined mass spectrometry approaches to identify lipids produced by the human gut symbiont Bacteroides thetaiotaomicron (B. theta) and spatially track these bacterial lipids in the mouse colon. We characterize 130 B. theta lipids by liquid chromatography-tandem mass spectrometry (LC-MS/MS), using wild-type and mutant B. theta strains to confidently identify lipid structures and their interconnected pathways in vitro. Of these, 103 B. theta lipids can be detected and spatially mapped in a single MALDI mass spectrometry imaging run. We map unlabeled bacterial lipids across colon sections of germ-free and specific-pathogen-free (SPF) mice and mice mono-colonized with wild-type or sphingolipid-deficient (BTMUT) B. theta. We observe co-localization of bacterially derived phosphatidic acid with host tissues in BTMUT mice, consistent with lipid penetration into host tissues. These results indicate limited and selective transfer of bacterial lipids to the host.


Assuntos
Bacteroides thetaiotaomicron , Colo , Microbioma Gastrointestinal , Lipidômica , Animais , Camundongos , Bacteroides thetaiotaomicron/metabolismo , Microbioma Gastrointestinal/fisiologia , Colo/microbiologia , Colo/metabolismo , Lipídeos/análise , Espectrometria de Massas em Tandem , Cromatografia Líquida , Metabolismo dos Lipídeos , Vida Livre de Germes , Organismos Livres de Patógenos Específicos , Ácidos Fosfatídicos/metabolismo , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Esfingolipídeos/metabolismo , Camundongos Endogâmicos C57BL , Feminino
17.
Food Funct ; 15(12): 6512-6522, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38804915

RESUMO

Children with Cystic Fibrosis (CF) are more likely to have intestinal dysbiosis due to recurrent antibiotic therapy and the conventional hypercaloric diet administered to them. This study aimed at evaluating the effect of isolated prebiotic components and probiotic strains, and their combinations as potential synbiotics, on the intestinal microbiota of CF children. A static in vitro colonic fermentation model was used by colonizing vials with faecal inoculum, a culture medium, and the substrates to be tested. Post treatment, aliquots were taken to determine ammonium, lactate, and short-chain fatty acids production and to profile the microbiota composition by 16s rRNA sequencing. At genus level, Escherichia-Shigella decreased (15.8%) with the treatment pectin + L. rhamnosus, followed by the beta-glucan + L. salivarius (15.5%). Inversely, the most increase in Bacteroides (44%) was obtained by the treatment with Pectin + L. reuteri. Lactate and acetic acid production was significantly increased with prebiotics and their combinations with L. rhamnosus and L. salivarius. In conclusion, the use of beta-glucan and pectin in combination with probiotic strains from the Lactobacillaceae family suggest potential to modulate dysbiosis and metabolic activity on CF colonic microbiota, encouraging further studies in animal studies or clinical settings to confirm the findings in vivo.


Assuntos
Colo , Fibrose Cística , Microbioma Gastrointestinal , Prebióticos , Probióticos , Humanos , Fibrose Cística/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/farmacologia , Criança , Colo/microbiologia , Colo/metabolismo , Fezes/microbiologia , Masculino , Fermentação , Ácidos Graxos Voláteis/metabolismo , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/metabolismo , Feminino , Disbiose/microbiologia , Pectinas/metabolismo , Pectinas/farmacologia
18.
Food Funct ; 15(12): 6536-6552, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38807503

RESUMO

A total of ninety-six weaned piglets were assigned to four dietary treatments in a 2 × 2 design. The treatments included: a standard milk formula (CTR); CTR + probiotics (6.4 × 108 cfu L-1Bifidobacterium longum subsp. infantis CECT 7210 and 1.1 × 108 cfu L-1Lactobacillus rhamnosus NH001) + prebiotics (galacto-oligosaccharides 4.36 g L-1 and human-milk-oligosaccharide 0.54 g L-1) (SYN); CTR + osteopontin (0.43 g L-1) (OPN); and CTR + SYN + OPN (CON). Daily records including feed intake, body weight, and clinical signs, were maintained throughout the 15-day trial. At the end of the study samples from blood, digestive content, and gut tissues were collected to determine serum TNF-α, intestinal fermentative activity (SCFA and ammonia), colonic microbiota (16S rRNA Illumina-MiSeq), histomorphology, and jejunal gene expression (Open-Array). No statistical differences were found in weight gain; however, the animals supplemented with osteopontin exhibited higher feed intake. In terms of clinical signs, synbiotic supplementation led to a shorter duration of diarrhoea episodes. Regarding gut health, the sequenced faecal microbiota revealed better control of potentially dysbiotic bacteria with the CON diet at day 15. In the colon compartment, a significant increase in SCFA concentration, a decrease in ammonia concentration, and a significant decrease in intraepithelial lymphocyte counts were particularly observed in CON animals. The supplemented diets were also associated with modified jejunal gene expression. The synbiotic combination was characterized by the upregulation of genes related to intestinal maturation (ALPI, SI) and nutrient transport (SLC13A1, SLC15A1, SLC5A1, SLC7A8), and the downregulation of genes related to the response to pathogens (GBP1, IDO, TLR4) or the inflammatory response (IDO, IL-1ß, TGF-ß1). Osteopontin promoted the upregulation of a digestive function gene (GCG). Correlational analysis between the microbiota population and various intestinal environmental factors (SCFA concentration, histology, and gene expression) proposes mechanisms of communication between the gut microbiota and the host. In summary, these results suggest an improvement in the colonic colonization process and a better modulation of the immune response when milk formula is supplemented with the tested synbiotic combined with osteopontin, benefiting from a synergistic effect.


Assuntos
Colo , Microbioma Gastrointestinal , Jejuno , Osteopontina , Simbióticos , Animais , Simbióticos/administração & dosagem , Suínos , Colo/microbiologia , Colo/metabolismo , Osteopontina/metabolismo , Osteopontina/genética , Jejuno/metabolismo , Jejuno/microbiologia , Lactação , Fórmulas Infantis , Feminino , Humanos , Prebióticos , Ração Animal/análise , Suplementos Nutricionais , Probióticos/farmacologia
19.
mSystems ; 9(6): e0004824, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38767377

RESUMO

Probiotics and synbiotics have been intensively used in animal husbandry due to their advantageous roles in animals' health. However, there is a paucity of research on probiotic and synbiotic supplementation from maternal gestation to the postnatal growing phases of offspring piglets. Thus, we assessed the effects of dietary supplementation of these two additives to sows and offspring piglets on skeletal muscle and body metabolism, colonic microbiota composition, and metabolite profiles of offspring piglets. Pregnant Bama mini-pigs and their offspring piglets (after weaning) were fed either a basal diet or a basal diet supplemented with antibiotics, probiotics, or synbiotics. At 65, 95, and 125 days old, eight pigs per group were euthanized and sampled for analyses. Probiotics increased the intramuscular fat content in the psoas major muscle (PMM) at 95 days old, polyunsaturated fatty acid (PUFA) and n-3 PUFA levels in the longissimus dorsi muscle (LDM) at 65 days old, C16:1 level in the LDM at 125 days old, and upregulated ATGL, CPT-1, and HSL expressions in the PMM at 65 days old. Synbiotics increased the plasma HDL-C level at 65 days old and TC level at 65 and 125 days old and upregulated the CPT-1 expression in the PMM at 125 days old. In addition, probiotics and synbiotics increased the plasma levels of HDL-C at 65 days old, CHE at 95 days old, and LDL-C at 125 days old, while decreasing the C18:1n9t level in the PMM at 65 days old and the plasma levels of GLU, LDH, and TG at 95 days old. Microbiome analysis showed that probiotic and synbiotic supplementation increased colonic Actinobacteria, Firmicutes, Verrucomicrobia, Faecalibacterium, Pseudobutyrivibrio, and Turicibacter abundances. However, antibiotic supplementation decreased colonic Actinobacteria, Bacteroidetes, Prevotella, and Unclassified_Lachnospiraceae abundances. Furthermore, probiotic and synbiotic supplementation was associated with alterations in 8, 7, and 10 differential metabolites at three different age stages. Both microbiome and metabolome analyses showed that the differential metabolic pathways were associated with carbohydrate, amino acid, and lipid metabolism. However, antibiotic supplementation increased the C18:1n9t level in the PMM at 65 days old and xenobiotic biodegradation and metabolism at 125 days old. In conclusion, sow-offspring's diets supplemented with these two additives showed conducive effects on meat flavor, nutritional composition of skeletal muscles, and body metabolism, which may be associated with the reshaping of colonic microbiota and metabolites. However, antibiotic supplementation has negative effects on colonic microbiota composition and fatty acid composition in the PMM. IMPORTANCE: The integral sow-offspring probiotic and synbiotic supplementation improves the meat flavor and the fatty acid composition of the LDM to some extent. Sow-offspring probiotic and synbiotic supplementation increases the colonic beneficial bacteria (including Firmicutes, Verrucomicrobia, Actinobacteria, Faecalibacterium, Turicibacter, and Pseudobutyrivibrio) and alters the colonic metabolite profiles, such as guanidoacetic acid, beta-sitosterol, inosine, cellobiose, indole, and polyamine. Antibiotic supplementation in sow-offspring's diets decreases several beneficial bacteria (including Bacteroidetes, Actinobacteria, Unclassified_Lachnospiraceae, and Prevotella) and has a favorable effect on improving the fatty acid composition of the LDM to some extent, while presenting the opposite effect on the PMM.


Assuntos
Suplementos Nutricionais , Microbioma Gastrointestinal , Metabolismo dos Lipídeos , Músculo Esquelético , Probióticos , Simbióticos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/fisiologia , Feminino , Suínos , Simbióticos/administração & dosagem , Probióticos/administração & dosagem , Probióticos/farmacologia , Gravidez , Músculo Esquelético/metabolismo , Músculo Esquelético/microbiologia , Músculo Esquelético/efeitos dos fármacos , Colo/microbiologia , Colo/metabolismo
20.
Int Immunopharmacol ; 135: 112285, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38762922

RESUMO

Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal inflammation regulated by intricate mechanisms. Recently, prebiotics is considered as promising nutritional strategy for the prevention and treatment of IBD. Prevotella histicola (P. histicola), an emerging probiotic, possesses apparently anti-inflammatory bioactivity. However, the role and underlying mechanism of P. histicola on IBD remain unclear. Hence, we probe into the effect of P. histicola on dextran sulfate sodium (DSS)-induced colitis and clarified the potential mechanism. Our results revealed that DSS-induced colonic inflammatory response and damaged epithelial barrier in mice were attenuated by oral administration of P. histicola. Moreover, supplementary P. histicola significantly enriched short-chain fatty acid (SCFA)-producing bacteria (Lactobacillus, and Bacillus) and reduced pathogenic bacteria (Erysipelotrichaceae, Clostridium, Bacteroides) in DSS-induced colitis. Notably, In DSS-treated mice, endoplasmic reticulum stress (ERS) was persistently activated in colonic tissue. Conversely, P. histicola gavage suppressed expansion of endoplasmic reticulum, downregulated PERK-ATF4-CHOP and IRE1α-JNK pathway. In vitro, the P. histicola supernatant eliminated LPS-induced higher production of pro-inflammatory cytokines regulated by NF-κB and impairment of epithelial barrier by inhibiting IRE1α-JNK signaling in Caco-2 cell. In summary, our study indicated that P. histicola mitigated DSS-induced chronic colitis via inhibiting IRE1α-JNK pathway and NF-κB signaling. These findings provide the new insights into the promotion of gut homeostasis and the application potential of P. histicola as a prebiotic for IBD in the future.


Assuntos
Colite , Sulfato de Dextrana , Estresse do Retículo Endoplasmático , Endorribonucleases , Camundongos Endogâmicos C57BL , NF-kappa B , Prevotella , Proteínas Serina-Treonina Quinases , Animais , Colite/induzido quimicamente , Colite/microbiologia , Colite/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , NF-kappa B/metabolismo , Camundongos , Endorribonucleases/metabolismo , Humanos , Probióticos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Masculino , Colo/patologia , Colo/microbiologia , Colo/efeitos dos fármacos , Colo/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças
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