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1.
Cell ; 185(3): 513-529.e21, 2022 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-35120663

RESUMEN

The human gut microbiota resides within a diverse chemical environment challenging our ability to understand the forces shaping this ecosystem. Here, we reveal that fitness of the Bacteroidales, the dominant order of bacteria in the human gut, is an emergent property of glycans and one specific metabolite, butyrate. Distinct sugars serve as strain-variable fitness switches activating context-dependent inhibitory functions of butyrate. Differential fitness effects of butyrate within the Bacteroides are mediated by species-level variation in Acyl-CoA thioesterase activity and nucleotide polymorphisms regulating an Acyl-CoA transferase. Using in vivo multi-omic profiles, we demonstrate Bacteroides fitness in the human gut is associated together, but not independently, with Acyl-CoA transferase expression and butyrate. Our data reveal that each strain of the Bacteroides exists within a unique fitness landscape based on the interaction of chemical components unpredictable by the effect of each part alone mediated by flexibility in the core genome.


Asunto(s)
Microbioma Gastrointestinal , Metaboloma , Polisacáridos/metabolismo , Acilcoenzima A/metabolismo , Secuencia de Aminoácidos , Aminoácidos de Cadena Ramificada/metabolismo , Bacteroidetes/efectos de los fármacos , Bacteroidetes/genética , Bacteroidetes/crecimiento & desarrollo , Butiratos/química , Butiratos/farmacología , Coenzima A Transferasas/química , Coenzima A Transferasas/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/genética , Variación Genética/efectos de los fármacos , Concentración de Iones de Hidrógeno , Metaboloma/efectos de los fármacos , Metaboloma/genética , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Especificidad de la Especie , Estrés Fisiológico/efectos de los fármacos , Estrés Fisiológico/genética , Transcripción Genética/efectos de los fármacos
2.
Cell ; 173(7): 1742-1754.e17, 2018 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-29906449

RESUMEN

Osmotic diarrhea is a prevalent condition in humans caused by food intolerance, malabsorption, and widespread laxative use. Here, we assess the resilience of the gut ecosystem to osmotic perturbation at multiple length and timescales using mice as model hosts. Osmotic stress caused reproducible extinction of highly abundant taxa and expansion of less prevalent members in human and mouse microbiotas. Quantitative imaging revealed decimation of the mucus barrier during osmotic perturbation, followed by recovery. The immune system exhibited temporary changes in cytokine levels and a lasting IgG response against commensal bacteria. Increased osmolality prevented growth of commensal strains in vitro, revealing one mechanism contributing to extinction. Environmental availability of microbiota members mitigated extinction events, demonstrating how species reintroduction can affect community resilience. Our findings (1) demonstrate that even mild osmotic diarrhea can cause lasting changes to the microbiota and host and (2) lay the foundation for interventions that increase system-wide resilience.


Asunto(s)
Diarrea/patología , Microbioma Gastrointestinal/efectos de los fármacos , Polietilenglicoles/farmacología , Animales , Bacteroidetes/efectos de los fármacos , Bacteroidetes/genética , Bacteroidetes/aislamiento & purificación , Ciego/química , Ciego/metabolismo , Ciego/microbiología , Ciego/patología , Colon/química , Colon/microbiología , Colon/patología , Citocinas/metabolismo , Diarrea/inmunología , Diarrea/microbiología , Diarrea/veterinaria , Heces/microbiología , Glicósido Hidrolasas/metabolismo , Humanos , Inmunidad Humoral/efectos de los fármacos , Inmunoglobulina G/metabolismo , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Metagenómica , Ratones , Concentración Osmolar , Polietilenglicoles/metabolismo , Proteoma/análisis , ARN Ribosómico 16S/química , ARN Ribosómico 16S/genética , Verrucomicrobia/efectos de los fármacos , Verrucomicrobia/genética , Verrucomicrobia/aislamiento & purificación
3.
FASEB J ; 38(8): e23603, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38648368

RESUMEN

Recent evidence suggests that chronic exposure to opioid analgesics such as morphine disrupts the intestinal epithelial layer and causes intestinal dysbiosis. Depleting gut bacteria can preclude the development of tolerance to opioid-induced antinociception, suggesting an important role of the gut-brain axis in mediating opioid effects. The mechanism underlying opioid-induced dysbiosis, however, remains unclear. Host-produced antimicrobial peptides (AMPs) are critical for the integrity of the intestinal epithelial barrier as they prevent the pathogenesis of the enteric microbiota. Here, we report that chronic morphine or fentanyl exposure reduces the antimicrobial activity in the ileum, resulting in changes in the composition of bacteria. Fecal samples from morphine-treated mice had increased levels of Akkermansia muciniphila with a shift in the abundance ratio of Firmicutes and Bacteroidetes. Fecal microbial transplant (FMT) from morphine-naïve mice or oral supplementation with butyrate restored (a) the antimicrobial activity, (b) the expression of the antimicrobial peptide, Reg3γ, (c) prevented the increase in intestinal permeability and (d) prevented the development of antinociceptive tolerance in morphine-dependent mice. Improved epithelial barrier function with FMT or butyrate prevented the enrichment of the mucin-degrading A. muciniphila in morphine-dependent mice. These data implicate impairment of the antimicrobial activity of the intestinal epithelium as a mechanism by which opioids disrupt the microbiota-gut-brain axis.


Asunto(s)
Analgésicos Opioides , Disbiosis , Fentanilo , Microbioma Gastrointestinal , Mucosa Intestinal , Ratones Endogámicos C57BL , Morfina , Animales , Morfina/farmacología , Ratones , Disbiosis/inducido químicamente , Disbiosis/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/microbiología , Masculino , Fentanilo/farmacología , Analgésicos Opioides/farmacología , Eje Cerebro-Intestino/efectos de los fármacos , Trasplante de Microbiota Fecal , Proteínas Asociadas a Pancreatitis/metabolismo , Akkermansia/efectos de los fármacos , Péptidos Antimicrobianos/farmacología , Bacteroidetes/efectos de los fármacos
4.
BMC Microbiol ; 24(1): 283, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39085808

RESUMEN

BACKGROUND: The guts of mammals are home to trillions of microbes, forming a complex and dynamic ecosystem. Gut microbiota is an important biological barrier for maintaining immune homeostasis. Recently, the use of antibiotics to clear gut microbiota has gained popularity as a low cost and easy-to-use alternative to germ-free animals. However, the effect of the duration of the antibiotic cocktail on the gut microbiome is unclear, and more importantly, the effect of dramatic changes in the gut microbiota on intestinal tissue morphology and local immune response is rarely reported. RESULTS: We observed a significant reduction in fecal microbiota species and abundance after 1 week of exposure to an antibiotic cocktail, gavage twice daily by intragastric administration. In terms of composition, Bacteroidetes and Firmicutes were replaced by Proteobacteria. Extending antibiotic exposure to 2-3 weeks did not significantly improve the overall efficiency of microbiotal consumption. No significant histomorphological changes were observed in the first 2 weeks of antibiotic cocktail exposure, but the expression of inflammatory mediators in intestinal tissue was increased after 3 weeks of antibiotic cocktail exposure. Mendelian randomization analysis showed that Actinobacteria had a significant causal association with the increase of IL-1ß (OR = 1.65, 95% CI = 1.23 to 2.21, P = 0.007) and TNF-α (OR = 1.81, 95% CI = 1.26 to 2.61, P = 0.001). CONCLUSIONS: Our data suggest that treatment with an antibiotic cocktail lasting 1 week is sufficient to induce a significant reduction in gut microbes. 3 weeks of antibiotic exposure can lead to the colonization of persistant microbiota and cause changes in intestinal tissue and local immune responses.


Asunto(s)
Antibacterianos , Heces , Microbioma Gastrointestinal , Antibacterianos/farmacología , Animales , Heces/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Interleucina-1beta/genética , Ratones , Bacterias/efectos de los fármacos , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Ratones Endogámicos C57BL , Bacteroidetes/efectos de los fármacos , Firmicutes/efectos de los fármacos
5.
Nature ; 529(7585): 212-5, 2016 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-26762459

RESUMEN

The gut is home to trillions of microorganisms that have fundamental roles in many aspects of human biology, including immune function and metabolism. The reduced diversity of the gut microbiota in Western populations compared to that in populations living traditional lifestyles presents the question of which factors have driven microbiota change during modernization. Microbiota-accessible carbohydrates (MACs) found in dietary fibre have a crucial involvement in shaping this microbial ecosystem, and are notably reduced in the Western diet (high in fat and simple carbohydrates, low in fibre) compared with a more traditional diet. Here we show that changes in the microbiota of mice consuming a low-MAC diet and harbouring a human microbiota are largely reversible within a single generation. However, over several generations, a low-MAC diet results in a progressive loss of diversity, which is not recoverable after the reintroduction of dietary MACs. To restore the microbiota to its original state requires the administration of missing taxa in combination with dietary MAC consumption. Our data illustrate that taxa driven to low abundance when dietary MACs are scarce are inefficiently transferred to the next generation, and are at increased risk of becoming extinct within an isolated population. As more diseases are linked to the Western microbiota and the microbiota is targeted therapeutically, microbiota reprogramming may need to involve strategies that incorporate dietary MACs as well as taxa not currently present in the Western gut.


Asunto(s)
Dieta/efectos adversos , Extinción Biológica , Microbioma Gastrointestinal , Adulto , Animales , Bacteroidetes/efectos de los fármacos , Carbohidratos de la Dieta/administración & dosificación , Fibras de la Dieta/administración & dosificación , Trasplante de Microbiota Fecal , Femenino , Fermentación/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/microbiología , Vida Libre de Gérmenes , Voluntarios Sanos , Humanos , Masculino , Ratones , Linaje
6.
BMC Microbiol ; 21(1): 166, 2021 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-34082715

RESUMEN

Antibiotic exposure during pregnancy will adversely affect the growth of offspring; however, this remains controversial and the mechanism is poorly understood. To study this phenomenon, we added ceftriaxone sodium to the drinking water of pregnant rats and continuously monitored the body weight of their offspring. The results showed that compared with the control group, the offspring exposed to antibiotics during pregnancy had a higher body weight up to 3 weeks old but had a lower body weight at 6 weeks old. To determine the role of the gut microbiota and its metabolites in the growth of offspring, we collected feces for sequencing and further established that the experimental group has a different composition ratio of dominant bacteria at 6 week old, among which S24-7 correlated negatively with body weight and the metabolites that correlated with body weight-related unique flora were L-Valine, L-Leucine, Glutaric acid, N-Acetyl-L-glutamate, and 5-Methylcytosine. To further explore how they affect the growth of offspring, we submitted these data to Kyoto Encyclopedia of Genes and Genomes website for relevant pathway analysis. The results showed that compared with the control, the following metabolic pathways changed significantly: Valine, leucine, and isoleucine biosynthesis; Protein digestion and absorption; and Mineral absorption. Therefore, we believe that our findings support the conclusion that ceftriaxone sodium exposure in pregnancy has a long-lasting adverse effect on the growth of offspring because of an imbalance of gut microbiota, especially S24-7, via different metabolic pathways.


Asunto(s)
Antibacterianos/efectos adversos , Bacteroidetes/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Ceftriaxona/efectos adversos , Microbioma Gastrointestinal/efectos de los fármacos , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal/microbiología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Animales , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/aislamiento & purificación , Bacteroidetes/clasificación , Bacteroidetes/genética , Bacteroidetes/aislamiento & purificación , Femenino , Humanos , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/etiología , Efectos Tardíos de la Exposición Prenatal/genética , Ratas , Ratas Sprague-Dawley
7.
Am J Drug Alcohol Abuse ; 46(1): 4-12, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31689142

RESUMEN

Background: A growing body of evidence highlights the role of the intestine in the development of various alcohol use disorder (AUD) complications. The intestinal microbiome has been proposed as an essential factor in mediating the development of AUD complications such as alcoholic liver disease.Objectives: To provide a comprehensive description of alcohol-induced intestinal microbiome alterations.Methods: We conducted a systematic review of studies investigating the effect of alcohol on the intestinal microbiome using the PRISMA checklist. We searched the Medline database on the PubMed platform for studies determining the effect of alcohol on microbiota in individuals with AUD. The manual search included references of retrieved articles. Only human studies examining the intestinal bacterial microbiome using 16S ribosomal RNA sequencing were included. Data comparing relative abundances of bacteria comprising intestinal microbiota was extracted.Results: We retrieved 17 studies investigating intestinal microbiome alterations in individuals with AUD. Intestinal microbiome alterations in individuals with AUD included depletion of Akkermansia muciniphila and Faecalibacterium prausnitzii and an increase of Enterobacteriaceae. At the phylum level, a higher abundance of Proteobacteria and lower of Bacteroidetes were found. Mixed results regarding Bifidobacterium were obtained. Several species of short-chain fatty acids producing bacteria had a lower abundance in individuals with alcohol use disorder.Conclusion: Intestinal microbiome alterations associated with dysbiosis in individuals with AUD are generally consistent across studies, making it a promising target in potential AUD complications treatment.


Asunto(s)
Alcoholismo/microbiología , Fenómenos Fisiológicos Bacterianos/efectos de los fármacos , Disbiosis/microbiología , Microbioma Gastrointestinal , Akkermansia/efectos de los fármacos , Bacterias/clasificación , Bacteroidetes/efectos de los fármacos , Enterobacteriaceae/efectos de los fármacos , Faecalibacterium/efectos de los fármacos , Fibrosis/microbiología , Hepatitis Alcohólica/microbiología , Humanos , Proteobacteria/efectos de los fármacos
8.
Anaerobe ; 66: 102283, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33022383

RESUMEN

Alistipes spp is a genus of Gram-negative anaerobic rods involved in very few human diseases. We report the first case of abdominal infection due to Alistipes onderdonkii in a 58-year-old man with a history of chronic obstructive pulmonary disease. He presented with abdominal pain and general malaise after retrogastric drainage for a pancreatitis episode a few days earlier. After the diagnosis of diffuse peritonitis with perforation and necrotizing pancreatic collection, abundant pancreatic fluid was drained and yielded the isolation of A. onderdonkii in pure culture. Resistance to penicillin and moxifloxacin was documented for this strain. Treatment with metronidazole was prescribed, and the patient was discharged after improvement of his general condition.


Asunto(s)
Bacteroidetes/clasificación , Infecciones Intraabdominales/diagnóstico , Infecciones Intraabdominales/microbiología , Anaerobiosis , Antibacterianos/uso terapéutico , Bacteroidetes/efectos de los fármacos , Bacteroidetes/genética , ADN Bacteriano , Humanos , Infecciones Intraabdominales/tratamiento farmacológico , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Peritonitis/diagnóstico , Peritonitis/microbiología , ARN Ribosómico 16S , Resultado del Tratamiento
9.
Anaerobe ; 61: 102145, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31918362

RESUMEN

Current research indicates that changes in gut microbiota can impact the host, but it is not always clear how dietary and environmental factors alter gut microbiota. One potential factor is antimicrobial activity of compounds ingested by the host. The goal of this study was to determine the antimicrobial activity of common plant secondary metabolites against pure cultures of paired, structurally and phylogenetically distinct gastrointestinal bacteria of human or bovine origin: Prevotella bryantii B14, Bacteroides fragilis 25285, Acetoanaerobium (Clostridium) sticklandii SR and Clostridioides difficile 9689. When growth media were amended with individual phytochemicals (the alkaloids: berberine, capsaicin, nicotine, piperine and quinine and the phenolic: curcumin), growth of each species was inhibited to varying degrees at the three greatest concentrations tested (0.10-10.00 mg mL-1). The viable cell numbers of all the cultures were reduced, ≥4-logs, by berberine at concentrations ≥1.00 mg mL-1. Quinine performed similarly to berberine for B14, 25285, and SR at the same concentrations. The other phytochemicals were inhibitory, but not as much as quinine or berberine. Nicotine had activity against all four species (≥2-log reduction in viable cell number at 10.00 mg mL-1), but had stronger activity against the Gram-positive bacteria, SR and 9689, (≥4-log reductions at 10.00 mg mL-1). In conclusion, the phytochemicals had varying spectra of antimicrobial activity. These results are consistent with the hypothesis that ingested phytochemicals have the ability to differentially impact gut microbiota through antimicrobial activity.


Asunto(s)
Antibacterianos/farmacología , Bacteroidetes/efectos de los fármacos , Firmicutes/efectos de los fármacos , Fitoquímicos/farmacología , Alcaloides/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana
10.
Molecules ; 25(3)2020 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-32033507

RESUMEN

The allicin diallyldisulfid-S-oxide, a major garlic organosulfur compound (OSC) in crushed garlic (Allium sativum L.), possesses antibacterial effects, and influences gut bacteria. In this study, we made allicin-free garlic (AFG) extract and investigated its effects on gut microbiome. C57BL/6N male mice were randomly divided into 6 groups and fed normal diet (ND) and high-fat diet (HFD) supplemented with or without AFG in concentrations of 1% and 5% for 11 weeks. The genomic DNAs of feces were used to identify the gut microbiome by sequencing 16S rRNA genes. The results revealed that the ratio of p-Firmicutes to p-Bacteroidetes increased by aging and HFD was reduced by AFG. In particular, the f-Lachnospiraceae, g-Akkermansia, and g-Lactobacillus decreased by aging and HFD was enhanced by AFG. The g-Dorea increased by aging and HFD decreased by AFG. In addition, the ratio of glutamic-pyruvic transaminase to glutamic-oxaloacetic transaminase (GPT/GOT) in serum was significantly increased in the HFD group and decreased by AFG. In summary, our data demonstrated that dietary intervention with AFG is a potential way to balance the gut microbiome disturbed by a high-fat diet.


Asunto(s)
Antibacterianos/farmacología , Suplementos Dietéticos , Ajo/química , Microbioma Gastrointestinal/efectos de los fármacos , Extractos Vegetales/farmacología , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Bacteroidetes/efectos de los fármacos , Bacteroidetes/aislamiento & purificación , Dieta Alta en Grasa , Disulfuros , Firmicutes/efectos de los fármacos , Firmicutes/aislamiento & purificación , Ajo/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ácidos Sulfínicos/análisis , Verrucomicrobia/efectos de los fármacos , Verrucomicrobia/aislamiento & purificación
11.
Artículo en Inglés | MEDLINE | ID: mdl-32998606

RESUMEN

Given the toxicity and widespread occurrence of hexavalent chromium [Cr(VI)] in aquatic environments, we investigated the feasibility of a down-flow hanging sponge (DHS) biofilm reactor for the enrichment of microbial communities capable of Cr(VI) removal. In the present study, a laboratory-scale DHS reactor fed with a molasses-based medium containing Cr(VI) was operated for 112 days for the investigation. The enrichment of Cr(VI)-removing microbial communities was evaluated based on water quality and prokaryotic community analyses. Once the DHS reactor began to operate, high average volumetric Cr(VI) removal rates of 1.21-1.45 mg L-sponge-1 h-1 were confirmed under varying influent Cr(VI) concentrations (approximately 20-40 mg L-1). 16S rRNA gene amplicon sequencing analysis suggested the presence of phylogenetically diverse prokaryotic lineages, including phyla that contain well-known Cr(VI)-reducing bacteria (e.g., Bacteroidetes, Firmicutes, and Proteobacteria) in the polyurethane sponge media of the DHS reactor. Therefore, our findings indicate that DHS reactors have great potential for the enrichment of Cr(VI)-removing microbial communities.


Asunto(s)
Biopelículas/crecimiento & desarrollo , Reactores Biológicos/microbiología , Cromo/análisis , Microbiota/efectos de los fármacos , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodos , Bacteroidetes/efectos de los fármacos , Firmicutes/efectos de los fármacos , Poliuretanos/química , Proteobacteria/efectos de los fármacos , ARN Ribosómico 16S/genética
12.
Gut ; 68(2): 248-262, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30007918

RESUMEN

OBJECTIVE: The medicinal fungus Ophiocordyceps sinensis and its anamorph Hirsutella sinensis have a long history of use in traditional Chinese medicine for their immunomodulatory properties. Alterations of the gut microbiota have been described in obesity and type 2 diabetes. We examined the possibility that H. sinensis mycelium (HSM) and isolated fractions containing polysaccharides may prevent diet-induced obesity and type 2 diabetes by modulating the composition of the gut microbiota. DESIGN: High-fat diet (HFD)-fed mice were treated with HSM or fractions containing polysaccharides of different molecular weights. The effects of HSM and polysaccharides on the gut microbiota were assessed by horizontal faecal microbiota transplantation (FMT), antibiotic treatment and 16S rDNA-based microbiota analysis. RESULTS: Fraction H1 containing high-molecular weight polysaccharides (>300 kDa) considerably reduced body weight gain (∼50% reduction) and metabolic disorders in HFD-fed mice. These effects were associated with increased expression of thermogenesis protein markers in adipose tissues, enhanced gut integrity, reduced intestinal and systemic inflammation and improved insulin sensitivity and lipid metabolism. Gut microbiota analysis revealed that H1 polysaccharides selectively promoted the growth of Parabacteroides goldsteinii, a commensal bacterium whose level was reduced in HFD-fed mice. FMT combined with antibiotic treatment showed that neomycin-sensitive gut bacteria negatively correlated with obesity traits and were required for H1's anti-obesogenic effects. Notably, oral treatment of HFD-fed mice with live P. goldsteinii reduced obesity and was associated with increased adipose tissue thermogenesis, enhanced intestinal integrity and reduced levels of inflammation and insulin resistance. CONCLUSIONS: HSM polysaccharides and the gut bacterium P. goldsteinii represent novel prebiotics and probiotics that may be used to treat obesity and type 2 diabetes.


Asunto(s)
Ascomicetos , Bacteroidetes/efectos de los fármacos , Bacteroidetes/fisiología , Diabetes Mellitus Tipo 2/prevención & control , Polisacáridos Fúngicos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Obesidad/prevención & control , Animales , Dieta Alta en Grasa , Trasplante de Microbiota Fecal , Resistencia a la Insulina , Masculino , Ratones , Ratones Endogámicos C57BL , Peso Molecular , Prebióticos , Simbiosis
13.
J Proteome Res ; 18(8): 3086-3098, 2019 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-31264424

RESUMEN

Increasing awareness of the importance of a healthy Bifidobacterium-rich microbiome has led to a need for more knowledge on how different prebiotic carbohydrates specifically impact the infant microbiome, especially as a community instead of single bacterial targets. In this study, we combined proton nuclear magnetic resonance (1H NMR) metabolomics and molecular biology methods for quantification of bacteria to compare the prebiotic effect of bovine milk oligosaccharides (BMO) and synthetic galacto oligosaccharides (GOS) using mono- and cocultures of eight major bacteria related to a healthy infant microbiome. The results revealed that BMO treatments supported growth of Bifidobacterium longum subsp. longum and Parabacteroides distasonis, while at the same time growth of Clostridium perfringens and Escherichia coli was inhibited. In addition, there was a synergistic effect of combining lactose and BMO in regards to reducing C. perfringens, maintaining stable numbers of P. distasonis and simultaneously increasing numbers of the beneficial B. longum subsp. longum. These results indicate that the oligosaccharide composition plays a vital role in shaping the developing microbiota.


Asunto(s)
Bifidobacterium/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Lactosa/metabolismo , Prebióticos/microbiología , Animales , Bacteroidetes/efectos de los fármacos , Bacteroidetes/crecimiento & desarrollo , Bifidobacterium/crecimiento & desarrollo , Bovinos , Clostridium perfringens/efectos de los fármacos , Clostridium perfringens/crecimiento & desarrollo , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Galactosa/metabolismo , Galactosa/farmacología , Microbioma Gastrointestinal/genética , Humanos , Lactante , Lactosa/farmacología , Espectroscopía de Resonancia Magnética , Leche/química , Leche/microbiología , Oligosacáridos/química , Oligosacáridos/farmacología
14.
Infect Immun ; 87(10)2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31308086

RESUMEN

As important players in the host defense system, commensal microbes and the microbiota influence multiple aspects of host physiology. Bordetella pertussis infection is highly contagious among humans. However, the roles of the microbiota in B. pertussis pathogenesis are poorly understood. Here, we show that antibiotic-mediated depletion of the microbiota results in increased susceptibility to B. pertussis infection during the early stage. The increased susceptibility was associated with a marked impairment of the systemic IgG, IgG2a, and IgG1 antibody responses to B. pertussis infection after antibiotic treatment. Furthermore, the microbiota impacted the short-lived plasma cell responses as well as the recall responses of memory B cells to B. pertussis infection. Finally, we found that the dysbiosis caused by antibiotic treatment affects CD4+ T cell generation and PD-1 expression on CD4+ T cells and thereby perturbs plasma cell differentiation. Our results have revealed the importance of commensal microbes in modulating host immune responses to B. pertussis infection and support the possibility of controlling the severity of B. pertussis infection in humans by manipulating the microbiota.


Asunto(s)
Bordetella pertussis/inmunología , Disbiosis/inmunología , Microbioma Gastrointestinal/inmunología , Inmunidad Humoral , Simbiosis/inmunología , Tos Ferina/inmunología , Ampicilina/farmacología , Animales , Antibacterianos/farmacología , Anticuerpos Antibacterianos/biosíntesis , Anticuerpos Antibacterianos/clasificación , Bacteroidetes/clasificación , Bacteroidetes/efectos de los fármacos , Bacteroidetes/crecimiento & desarrollo , Bacteroidetes/inmunología , Bordetella pertussis/crecimiento & desarrollo , Bordetella pertussis/patogenicidad , Disbiosis/microbiología , Disbiosis/fisiopatología , Femenino , Firmicutes/clasificación , Firmicutes/efectos de los fármacos , Firmicutes/crecimiento & desarrollo , Firmicutes/inmunología , Microbioma Gastrointestinal/efectos de los fármacos , Inmunidad Innata , Inmunoglobulina G/biosíntesis , Inmunoglobulina G/clasificación , Metronidazol/farmacología , Ratones , Ratones Endogámicos BALB C , Neomicina/farmacología , Proteobacteria/clasificación , Proteobacteria/efectos de los fármacos , Proteobacteria/crecimiento & desarrollo , Proteobacteria/inmunología , Simbiosis/efectos de los fármacos , Vancomicina/farmacología , Tos Ferina/microbiología , Tos Ferina/fisiopatología
15.
Pharmacol Res ; 148: 104460, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31560944

RESUMEN

Neohesperidin (NHP), derived from citrus fruits, has attracted considerable interest due to its preventative and therapeutic effects on numerous diseases. However, little progress has been made in determining the exact function of NHP on tumorigenesis. In the current study, we found that NHP inhibited colorectal tumorigenesis in the APC min/+ transgenic mouse model, as well as induced apoptosis and blocked angiogenesis in vivo. Our in-cell study suggested that this tumorigenic preventative effect of NHP is not due to the direct impact on tumor cells. Intriguingly, by utilizing 16 s rRNA gene-based microbiota sequencing, the relative abundance of Bacteroidetes was decreased, while Firmicutes and Proteobacteria were increased in the presence of NHP. Additionally, the fecal microbiota transplantation experiment further revealed that feeding with fecal of NHP-treated mice induced considerable inhibition of tumorigenesis, which indicates that the alteration of gut microbiota is responsible for NHP-mediated prevention of colorectal tumorigenesis. Thus, our study not only suggests the efficacy of NHP as a potent natural product for preventing colorectal cancer but also proposes a compelling model to connect the gut microbiota to the preventative effect of NHP on tumorigenesis.


Asunto(s)
Carcinogénesis/efectos de los fármacos , Neoplasias Colorrectales/prevención & control , Microbioma Gastrointestinal/efectos de los fármacos , Hesperidina/análogos & derivados , Animales , Bacteroidetes/efectos de los fármacos , Trasplante de Microbiota Fecal/métodos , Heces/microbiología , Firmicutes/efectos de los fármacos , Microbioma Gastrointestinal/genética , Hesperidina/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microbiota/efectos de los fármacos , Microbiota/genética , Proteobacteria/efectos de los fármacos , ARN Ribosómico 16S/genética
16.
Br J Nutr ; 121(5): 549-559, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30688188

RESUMEN

Wholegrain oats are known to modulate the human gut microbiota and have prebiotic properties (increase the growth of some health-promoting bacterial genera within the colon). Research to date mainly attributes these effects to the fibre content; however, oat is also a rich dietary source of polyphenols, which may contribute to the positive modulation of gut microbiota. In vitro anaerobic batch-culture experiments were performed over 24 h to evaluate the impact of two different doses (1 and 3 % (w/v)) of oat bran, matched concentrations of ß-glucan extract or polyphenol mix, on the human faecal microbiota composition using 16S RNA gene sequencing and SCFA analysis. Supplementation with oats increased the abundance of Proteobacteria (P <0·01) at 10 h, Bacteroidetes (P <0·05) at 24 h and concentrations of acetic and propionic acid increased at 10 and 24 h compared with the NC. Fermentation of the 1 % (w/v) oat bran resulted in significant increase in SCFA production at 24 h (86 (sd 27) v. 28 (sd 5) mm; P <0·05) and a bifidogenic effect, increasing the relative abundance of Bifidobacterium unassigned at 10 h and Bifidobacterium adolescentis (P <0·05) at 10 and 24 h compared with NC. Considering the ß-glucan treatment induced an increase in the phylum Bacteroidetes at 24 h, it explains the Bacteriodetes effects of oats as a food matrix. The polyphenol mix induced an increase in Enterobacteriaceae family at 24 h. In conclusion, in this study, we found that oats increased bifidobacteria, acetic acid and propionic acid, and this is mediated by the synergy of all oat compounds within the complex food matrix, rather than its main bioactive ß-glucan or polyphenols. Thus, oats as a whole food led to the greatest impact on the microbiota.


Asunto(s)
Avena/química , Bacteroidetes/efectos de los fármacos , Bifidobacterium/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Granos Enteros , Ácido Acético/metabolismo , Heces/microbiología , Fermentación/efectos de los fármacos , Humanos , Polifenoles/farmacología , Prebióticos , Propionatos/metabolismo , Proteobacteria/efectos de los fármacos , beta-Glucanos/farmacología
17.
Appl Microbiol Biotechnol ; 103(13): 5269-5283, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31020379

RESUMEN

Gut microbiota play a key role in the regulation of obesity and associated metabolic disorders. To study the relationship between them, antibiotics have been widely used to generate pseudo-germ-free rodents as control models. However, it is not clear whether antibiotics impact an animal's metabolic phenotype. Therefore, the effect of antibiotics-induced gut microbial perturbations on metabolic phenotypes in high-fat diet (HFD) fed mice was investigated. The results showed that antibiotics perturbed gut microbial composition and structure. Community diversity and richness were reduced, and the phyla Firmicutes/Bacteroidetes (F/B) ratio was decreased by antibiotics. Visualization of Unifrac distance data using principal component analysis (PCA) and unweighted pair-group method with arithmetic mean (UPGAM) demonstrated that fecal samples of HFD-fed mice separated from those of chow diet (CD) fed mice. Fecal samples from antibiotics-treated and non-treated mice were clustered into two different microbial populations. Moreover, antibiotics suppressed HFD-induced metabolic features, including body weight gain (BWG), liver weight (LW), epididymal fat weight (EFW), and serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), fasting blood glucose (FBG), and insulin (INS) significantly (P < 0.05). Lachnospiraceae, Ruminiclostridium and Helicobacter, biomarkers of mouse gut microbiota before treatment by antibiotics, were positively correlated with obesity phenotypes significantly (P < 0.05) and were decreased by (92.95 ± 5.09) %, (97.73 ± 2.09) % and (99.48 ± 0.21) % respectively after 30 days of treatment by antibiotics. However, Bacteroidia were enriched in HFD-fed antibiotics-treated mice and were negatively correlated with obesity phenotypes significantly (P < 0.05). We suggested that the antibiotics-induced depletion of Lachnospiraceae, Ruminiclostridium, and Helicobacter, and the decrease in F/B ratio in gut microbiota played a role in the prevention of HFD-induced obesity in mice.


Asunto(s)
Antibacterianos/administración & dosificación , Bacteroidetes/clasificación , Firmicutes/clasificación , Microbioma Gastrointestinal/efectos de los fármacos , Obesidad/microbiología , Animales , Bacteroidetes/efectos de los fármacos , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Heces/microbiología , Firmicutes/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Fenotipo
18.
Ecotoxicol Environ Saf ; 167: 44-53, 2019 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-30292975

RESUMEN

Soil bacterial communities have complex regulatory networks, which are mainly associated with soil fertility and ecological functions, and are likely to be disturbed due to antibiotics applications. The impact of antibiotics, particularly in mixtures form, on bacterial communities in different paddy soils is poorly understood. Using pyrosequencing techniques of 16 S rRNA genes, this study investigated the synergistic effects of veterinary antibiotics (sulfadiazine, sulfamethoxazole, trimethoprim, florfenicol, and clarithromycin) on bacterial communities in a soil-bacteria-plant system. Rice was grown under controlled greenhouse conditions where unplanted and planted treatments were doped with 200 µg kg-1 of combined antibiotics over a period of 3 months. Bacterial richness remained unaltered, while a significant decline was observed in bacterial diversity due to antibiotics in the four paddy soils. Bacteroidetes and Acidobacteria were increased, while Actinobacteria and Firmicutes decreased under antibiotics exposure. Despite antibiotics perturbation, compositional variations were mainly attributed to the different paddy soils which harbor distinct bacterial communities. Haliangium and Gaiella were among the sensitive genera that were negatively correlated to antibiotics perturbation. Additionally, electrical conductivity, total organic carbon, and total nitrogen of soil solution were the key physiochemical indices which significantly influenced the structure of bacterial communities in the paddy soils. These findings expanded our knowledge of effects from synergistic antibiotics application and variations in bacterial communities among different paddy soils.


Asunto(s)
Antibacterianos/análisis , Microbiología del Suelo , Drogas Veterinarias/análisis , Acidobacteria/efectos de los fármacos , Acidobacteria/aislamiento & purificación , Actinobacteria/efectos de los fármacos , Actinobacteria/aislamiento & purificación , Bacteroidetes/efectos de los fármacos , Bacteroidetes/aislamiento & purificación , Biodiversidad , Carbono/análisis , Firmicutes/efectos de los fármacos , Firmicutes/aislamiento & purificación , Nitrógeno/análisis , Oryza/microbiología , ARN Ribosómico 16S/genética , Suelo/química
19.
Int J Mol Sci ; 20(8)2019 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-31003566

RESUMEN

The development of prebiotic fibers requires fast high-throughput screening of their effects on the gut microbiota. We demonstrated the applicability of a mictotiter plate in the in vitro fermentation models for the screening of potentially-prebiotic dietary fibers. The effects of seven rye bran-, oat- and linseed-derived fiber preparations on the human fecal microbiota composition and short-chain fatty acid production were studied. The model was also used to study whether fibers can alleviate the harmful effects of amoxicillin-clavulanate on the microbiota. The antibiotic induced a shift in the bacterial community in the absence of fibers by decreasing the relative amounts of Bifidobacteriaceae, Bacteroidaceae, Prevotellaceae, Lachnospiraceae and Ruminococcaceae, and increasing proteobacterial Sutterilaceae levels from 1% to 11% of the total microbiota. The fermentation of rye bran, enzymatically treated rye bran, its insoluble fraction, soluble oat fiber and a mixture of rye fiber:soluble oat fiber:linseed resulted in a significant increase in butyrate production and a bifidogenic effect in the absence of the antibiotic. These fibers were also able to counteract the negative effects of the antibiotic and prevent the decrease in the relative amount of bifidobacteria. Insoluble and soluble rye bran fractions and soluble oat fiber were the best for controlling the level of proteobacteria at the level below 2%.


Asunto(s)
Fibras de la Dieta/metabolismo , Ácidos Grasos Volátiles/biosíntesis , Microbioma Gastrointestinal/efectos de los fármacos , Prebióticos/administración & dosificación , Bacteroidetes/efectos de los fármacos , Bacteroidetes/aislamiento & purificación , Bifidobacterium/efectos de los fármacos , Bifidobacterium/aislamiento & purificación , Ácidos Grasos Volátiles/administración & dosificación , Ácidos Grasos Volátiles/química , Heces/química , Fermentación , Humanos , Proteobacteria/efectos de los fármacos , Proteobacteria/aislamiento & purificación
20.
Int J Mol Sci ; 20(9)2019 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-31052157

RESUMEN

Detecting microbial interactions is essential to the understanding of the structure and function of the gut microbiome. In this study, microbial co-occurrence patterns were inferred using a random matrix theory based approach in the gut microbiome of mice in response to chondroitin sulfate disaccharide (CSD) under healthy and stressed conditions. The exercise stress disrupted the network composition and microbial co-occurrence patterns. Thirty-four Operational Taxonomic Units (OTU) were identified as module hubs and connectors, likely acting as generalists in the microbial community. Mucispirillum schaedleri acted as a connector in the stressed network in response to CSD supplement and may play a key role in bridging intimate interactions between the host and its microbiome. Several modules correlated with physiological parameters were detected. For example, Modules M02 (under stress) and S05 (stress + CSD) were strongly correlated with blood urea nitrogen levels (r = 0.90 and -0.75, respectively). A positive correlation between node connectivity of the OTUs assigned to Proteobacteria with superoxide dismutase activities under stress (r = 0.57, p < 0.05) provided further evidence that Proteobacteria can be developed as a potential pathological marker. Our findings provided novel insights into gut microbial interactions and may facilitate future endeavor in microbial community engineering.


Asunto(s)
Microbioma Gastrointestinal , Estrés Fisiológico , Actinobacteria/efectos de los fármacos , Actinobacteria/aislamiento & purificación , Animales , Bacteroidetes/efectos de los fármacos , Bacteroidetes/aislamiento & purificación , Sulfatos de Condroitina/efectos adversos , Ratones , Ratones Endogámicos BALB C , Esfuerzo Físico , Proteobacteria/efectos de los fármacos , Proteobacteria/aislamiento & purificación
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