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OBJECTIVE: To conduct an exploratory examination of dietary patterns and quality during pregnancy in African-American women who were class I, II, or III obese, and those women with normal pre-pregnancy body mass index (pBMI), as well to identify dietary factors associated with GWG, and changes in the distal gut microbiome. African American women represent the largest group affected by pre-pregnancy obesity, a risk factor for several adverse birth outcomes. METHODS: This prospective study investigated the association between diet, distal gut microbiome, and GWG among African-American women (n = 21) with obesity (n = 15) compared to women with a normal pre-pregnancy body mass index (pBMI) (n = 6) at two time points, 27-29 and 37-39 weeks gestation. Dietary patterns associated with obesity severity and GWG gain were assessed using Welch's T-test and Mann-Whitney U. The association between the gut microbiome and dietary patterns was assessed using a regression-based kernel association test and the adaptive microbiome-based sum of powered score test. RESULTS: In early pregnancy, dietary intake of Total Fruits and Greens and Beans was significantly different between pBMI and GWG groups; significance was 0.022 and 0.028 respectively. Women with Class II/III obesity and those with GWG above guidelines had Healthy Eating Index (HEI) scores below 50, meeting less than 75% of dietary guidelines, and did not meet recommendations for fruit and vegetable or fiber intake. We found no significant associations between the microbiome composition and diet (HEI Scores). CONCLUSIONS FOR PRACTICE: Overall, the results indicate that women with pBMI obesity are not meeting minimum dietary guidelines for nutrient intakes during pregnancy, specifically fruits, vegetables, and fiber, regardless of GWG. Interventions for African-American women with pre-pregnancy obesity, with a focus on increasing consumption of fruits and vegetables, would be beneficial to control GWG and improve birth outcomes.
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Microbioma Gastrointestinal , Ganho de Peso na Gestação , Complicações na Gravidez , Negro ou Afro-Americano , Índice de Massa Corporal , Dieta , Feminino , Humanos , Obesidade , Gravidez , Estudos Prospectivos , VerdurasRESUMO
Alterations in diversity and function of the gut microbiome are associated with concomitant changes in immune response, including chronic inflammation. Chronic inflammation is a major risk factor for colorectal cancer (CRC). An important component of the inflammatory response system are the toll-like receptors (TLRs). TLRs are capable of sensing microbial components, including nucleic acids, lipopolysaccharides and peptidoglycans, as well as bacterial outer membrane vesicles (OMV). OMVs can be decorated with or carry as cargo these TLR activating factors. These microbial factors can either promote tolerance or activate signaling pathways leading to chronic inflammation. Herein we discuss the role of the microbiome and the OMVs that originate from intestinal bacteria in promoting chronic inflammation and the development of colitis-associated CRC. We also discuss the contribution of TLRs in mediating the microbiome-inflammation axis and subsequent cancer development. Understanding the role of the microbiome and its secretory factors in TLR response may lead to the development of better cancer therapeutics.
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Neoplasias Colorretais/patologia , Microbioma Gastrointestinal , Inflamação/metabolismo , Receptores Toll-Like/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/microbiologia , HumanosRESUMO
OBJECTIVE: The current research examined the association between state disfavoured tax on soda (i.e. the difference between soda sales tax and the tax on food products generally) and a summary score representing the strength of state laws governing competitive beverages (beverages that compete with the beverages in the federally funded school lunch programme) in US schools. DESIGN: The Classification of Laws Associated with School Students (CLASS) summary score reflected the strength of a state's laws restricting competitive beverages sold in school stores, vending machines, school fundraisers and à la carte cafeteria items. Bridging the Gap (BTG) is a nationally recognized research initiative that provided state-level soda tax data. The main study outcome was the states' competitive beverage summary scores for elementary, middle and high school grade levels, as predicted by the states' disfavoured soda tax. Univariate and multivariate analyses were conducted, adjusting for year and state. SETTING: Data from BTG and CLASS were used. SUBJECTS: BTG and CLASS data from all fifty states and the District of Columbia from 2003 to 2010 were used. RESULTS: A higher disfavoured soda sales tax was generally associated with an increased likelihood of having strong school beverage laws across grade levels, and especially when disfavoured soda sales tax was >5 %. CONCLUSIONS: These data suggest a concordance between states' soda taxes and laws governing beverages sold in schools. States with high disfavoured sales tax on soda had stronger competitive beverage laws, indicating that the state sales tax environment may be associated with laws governing beverage policy in schools.
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Bebidas Gaseificadas/efeitos adversos , Serviços de Alimentação , Modelos Econômicos , Política Nutricional , Instituições Acadêmicas , Impostos , Adolescente , Bebidas Gaseificadas/economia , Criança , Distribuidores Automáticos de Alimentos/economia , Distribuidores Automáticos de Alimentos/legislação & jurisprudência , Serviços de Alimentação/economia , Serviços de Alimentação/legislação & jurisprudência , Fidelidade a Diretrizes , Humanos , Política Nutricional/legislação & jurisprudência , Guias de Prática Clínica como Assunto , Instituições Acadêmicas/economia , Instituições Acadêmicas/legislação & jurisprudência , Governo Estadual , Impostos/economia , Impostos/legislação & jurisprudência , Estados Unidos , Adulto JovemRESUMO
Change within the intratumoral microbiome is a common feature in lung and other cancers and may influence inflammation and immunity in the tumor microenvironment, affecting growth and metastases. We previously characterized the lung cancer microbiome in patients and identified Acidovorax temperans as enriched in tumors. Here, we instilled A. temperans in an animal model driven by mutant K-ras and Tp53. This revealed A. temperans accelerates tumor development and burden through infiltration of proinflammatory cells. Neutrophils exposed to A. temperans displayed a mature, pro-tumorigenic phenotype with increased cytokine signaling, with a global shift away from IL-1ß signaling. Neutrophil to monocyte and macrophage signaling upregulated MHC II to activate CD4+ T cells, polarizing them to an IL-17A+ phenotype detectable in CD4+ and γδ populations (T17). These T17 cells shared a common gene expression program predictive of poor survival in human LUAD. These data indicate bacterial exposure promotes tumor growth by modulating inflammation.
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Biological nanoparticles, such as bacterial outer membrane vesicles (OMVs), are routinely characterized through transmission electron microscopy (TEM). In this study, we report a novel method to prepare OMVs for TEM imaging. To preserve vesicular shape and structure, we developed a dual fixation protocol involving osmium tetroxide incubation prior to negative staining with uranyl acetate. Combining osmium tetroxide with uranyl acetate resulted in preservation of sub-50 nm vesicles and improved morphological stability, enhancing characterization of lipid-based nanoparticles by TEM.
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Corantes , Tetróxido de Ósmio , Microscopia Eletrônica , Membrana Externa Bacteriana , Microscopia Eletrônica de Transmissão , Coloração e Rotulagem , OsmioRESUMO
Intratumoral microbes may have multifunctional roles in carcinogenesis. Microsatellite instability (MSI) is associated with higher tumor immunity and mutational burden. Using whole transcriptome and whole genome sequencing microbial abundance data, we investigated associations of intratumoral microbes with MSI, survival, and MSI-relevant tumor molecular characteristics across multiple cancer types including colorectal cancer (CRC), stomach adenocarcinoma, and endometrial carcinoma. Among 451 CRC patients, our key finding was strong associations of multiple CRC-associated genera, including Dialister and Casatella, with MSI. Dialister and Casatella abundance was associated with improved overall survival (hazard ratiomortality = 0.56, 95% confidence interval = 0.34 to 0.92, and hazard ratiomortality = 0.44, 95% confidence interval = 0.27 to 0.72), respectively, comparing higher relative to lower quantiles. Multiple intratumor microbes were associated with immune genes and tumor mutational burden. Diversity of oral cavity-originating microbes was also associated with MSI among CRC and stomach adenocarcinoma patients. Overall, our findings suggest the intratumor microbiota may differ by MSI status and play a role in influencing the tumor microenvironment.
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Adenocarcinoma , Neoplasias Colorretais , Neoplasias Gástricas , Humanos , Instabilidade de Microssatélites , Neoplasias Colorretais/patologia , Neoplasias Gástricas/genética , Adenocarcinoma/genética , Microambiente Tumoral/genéticaRESUMO
Helicobacter pylori is the primary cause of 78% of gastric cancer cases, providing an opportunity to prevent cancer by controlling a single bacterial pathogen within the complex gastric microbiota. We developed highly selective antimicrobial agents against H. pylori by fusing an H. pylori-binding guide peptide (MM1) to broad-spectrum antimicrobial peptides. The common dairy probiotic Lactococcus lactis was then engineered to secrete these guided antimicrobial peptides (gAMPs). When co-cultured in vitro with H. pylori, the gAMP probiotics lost no toxicity compared to unguided AMP probiotics against the target, H. pylori, while losing >90% of their toxicity against two tested off-target bacteria. To test binding to H. pylori, the MM1 guide was fused to green fluorescent protein (GFP), resulting in enhanced binding compared to unguided GFP as measured by flow cytometry. In contrast, MM1-GFP showed no increased binding over GFP against five different off-target bacteria. These highly selective gAMP probiotics were then tested by oral gavage in mice infected with H. pylori. As a therapy, the probiotics outperformed antibiotic treatment, effectively eliminating H. pylori in just 5 days, and also protected mice from challenge infection as a prophylactic. As expected, the gAMP probiotics were as toxic against H. pylori as the unguided AMP probiotics. However, a strong rebound in gastric species diversity was found with both the selective gAMP probiotics and the non-selective AMP probiotics. Eliminating the extreme microbial dysbiosis caused by H. pylori appeared to be the major factor in diversity recovery. IMPORTANCE Alternatives to antibiotics in the control of Helicobacter pylori and the prevention of gastric cancer are needed. The high prevalence of H. pylori in the human population, the induction of microbial dysbiosis by antibiotics, and increasing antibiotic resistance call for a more sustainable approach. By selectively eliminating the pathogen and retaining the commensal community, H. pylori control may be achieved without adverse health outcomes. Antibiotics are typically used as a therapeutic post-infection, but a more targeted, less disruptive approach could be used as a long-term prophylactic against H. pylori or, by extension, against other gastrointestinal pathogens. Furthermore, the modular nature of the guided antimicrobial peptide (gAMP) technology allows for the substitution of different guides for different pathogens and the use of a cocktail of gAMPs to avoid the development of pathogen resistance.
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Obesity-associated inflammation and/or oxidative stress can damage intramuscular proteins and jeopardize muscle integrity. The immunoproteasome (iProt) is vital to remove oxidatively modified proteins, but this function may be compromised with obesity. We sought to elucidate whether diet-induced obesity alters intramuscular iProt content and activity in mice to identify a possible mechanism for impaired muscle proteostasis in the obese state. Total proteasome content and activity and estimates of muscle oxidative damage, inflammation, muscle mass and strength were also assessed. Twenty-three male, 5-week-old C57BL/6J mice were fed a high-fat, high-sucrose (HFS; 45% kcal fat, 17% sucrose, n = 12) or low-fat, low-sucrose (LFS; 10% kcal fat, 0% sucrose, n = 11) diet for 12 weeks. Strength was assessed via a weightlifting test. Despite no change in pro-inflammatory cytokines (P > 0.05), oxidative protein damage was elevated within the gastrocnemius (P = 0.036) and tibialis anterior (P = 0.033) muscles of HFS-fed mice. Intramuscular protein damage coincided with reduced iProt and total proteasome activity (P < 0.05), and reductions in relative muscle mass (P < 0.001). Therefore, proteasome dysregulation occurs in obese muscle and may be a critical link in muscle oxidative stress. Novelty: Our results show for the first time that immunoproteasome and total proteasome function is significantly reduced within obese muscle. Visceral fat mass is a significant predictor of diminished proteasome activity in skeletal muscle. Proteasome function is inversely correlated with an intramuscular accumulation of oxidatively damaged proteins.
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Complexo de Endopeptidases do Proteassoma , Proteostase , Animais , Dieta Hiperlipídica , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , SacaroseRESUMO
Dietary patterns contribute to cancer risk. Separately, microbial factors influence the development of several cancers. However, the interaction of diet and the microbiome and their joint contribution to cancer treatment response needs more research. The microbiome significantly impacts drug metabolism, immune activation, and response to immunotherapy. One of the critical factors affecting the microbiome structure and function is diet. Data demonstrate that the diet and microbiome composition affects the immune response. Moreover, malnutrition is a significant confounder to cancer therapy response. There is little understanding of the interaction of malnutrition with the microbiome in the context of cancer. This review aims to address the current knowledge of dietary intake patterns and malnutrition among cancer patients and the impact on treatment outcomes. Second, this review will provide evidence linking the microbiome to cancer treatment response and provide evidence of the potentially strong effect that diet could have on this interaction. This review will formulate critical questions that will need further research to understand the diet-microbiome relationship in cancer treatment response and directions for future research to guide us to precision nutrition therapy to improve cancer outcomes.
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Microbioma Gastrointestinal , Desnutrição , Microbiota , Neoplasias , Dieta , Microbioma Gastrointestinal/fisiologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Estado NutricionalRESUMO
Tryptophan metabolism, via the kynurenine (Kyn) pathway, and microbial transformation of tryptophan to indolic compounds are fundamental for host health; both of which are altered in colon carcinogenesis. Alterations in tryptophan metabolism begin early in colon carcinogenesis as an adaptive mechanism for the tumor to escape immune surveillance and metastasize. The microbial community is a key part of the tumor microenvironment and influences cancer initiation, promotion and treatment response. A growing awareness of the impact of the microbiome on tryptophan (Trp) metabolism in the context of carcinogenesis has prompted this review. We first compare the different metabolic pathways of Trp under normal cellular physiology to colon carcinogenesis, in both the host cells and the microbiome. Second, we review how the microbiome, specifically indoles, influence host tryptophan pathways under normal and oncogenic metabolism. We conclude by proposing several dietary, microbial and drug therapeutic modalities that can be utilized in combination to abrogate tumorigenesis.
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Carcinogênese/metabolismo , Neoplasias do Colo/terapia , Microbioma Gastrointestinal/efeitos dos fármacos , Triptofano/metabolismo , Evasão Tumoral/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinogênese/efeitos dos fármacos , Carcinogênese/imunologia , Colo/microbiologia , Colo/patologia , Neoplasias do Colo/imunologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/microbiologia , Terapia Combinada/métodos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Microbioma Gastrointestinal/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Indóis/administração & dosagem , Indóis/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Cinurenina/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/imunologia , Probióticos/administração & dosagem , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/metabolismo , Receptores de Hidrocarboneto Arílico/antagonistas & inibidores , Receptores de Hidrocarboneto Arílico/metabolismo , Simbiose/imunologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologiaRESUMO
A recent study by Montalban-Arques et al.1 in Cell Host & Microbe shows that augmenting the function of the gut microbiota reduces tumor burden. Four Clostridiales species blocked tumor growth as efficient as chemotherapy or immunotherapy in colorectal cancer and melanoma.
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Microbioma Gastrointestinal , Melanoma , Bactérias , Humanos , Imunoterapia , Melanoma/terapia , Linfócitos TRESUMO
A recent study in Nature finds significant shifts in the gut microbiome of post-menopausal women on severe calorie restriction concomitant with weight loss. Microbiota transplantation to germ-free mice display a similar weight loss, along with a bloom in C. difficile, unlocking clues to microbial metabolic alteration in weight loss.
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Bactérias/patogenicidade , Restrição Calórica , Microbioma Gastrointestinal , Animais , Clostridioides difficile , Transplante de Microbiota Fecal , Fezes/microbiologia , Vida Livre de Germes , Humanos , Camundongos , Obesidade/microbiologia , Redução de PesoRESUMO
Peripheral artery disease (PAD) affects over 200 million people worldwide, resulting in significant morbidity and mortality, yet treatment options remain limited. Among the manifestations of PAD is a severe functional disability and decline, which is thought to be the result of different pathophysiological mechanisms including oxidative stress, skeletal muscle pathology, and reduced nitric oxide bioavailability. Thus, compounds that target these mechanisms may have a therapeutic effect on walking performance in PAD patients. Phytochemicals produced by plants have been widely studied for their potential health effects and role in various diseases including cardiovascular disease and cancer. In this review, we focus on PAD and discuss the evidence related to the clinical utility of different phytochemicals. We discuss phytochemical research in preclinical models of PAD, and we highlight the results of the available clinical trials that have assessed the effects of these compounds on PAD patient functional outcomes.
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Doença Arterial Periférica/terapia , Compostos Fitoquímicos/uso terapêutico , Animais , Ensaios Clínicos como Assunto , Humanos , Terapia Nutricional/métodosRESUMO
A paper published in Science probes over 1500 tumor samples from multiple cancer types for markers of a tumor microbiome and viable bacteria. Unique intertumoral and intracellular signatures associated with clinical biomarkers and metabolic pathways provide clues to the roles bacteria play in carcinogenesis.
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Microbiota , Neoplasias , Bactérias/genética , Carcinogênese , HumanosRESUMO
Following publication of the original paper [1], the authors submitted a new Additional file 5 to replace the one containing formatting issues. The updated Additional file 5 is published in this correction.
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Gut microbial composition has shown to be associated with obesity, diabetes mellitus, inflammatory bowel disease, colitis, autoimmune disorders, and cancer, among other diseases. Microbiome research has significantly evolved through the years and continues to advance as we develop new and better strategies to more accurately measure its composition and function. Careful selection of study design, inclusion and exclusion criteria of participants, and methodology are paramount to accurately analyze microbial structure. Here we present the most up-to-date available information on methods for gut microbial collection and analysis.
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Metagenoma , Metagenômica , Microbiota , Pesquisa , Evolução Biológica , Microbioma Gastrointestinal , Humanos , Metagenômica/métodos , Reação em Cadeia da Polimerase , RNA Ribossômico 16SRESUMO
Among the laboratory and bioinformatic processing steps for human microbiome studies, a lack of consistency in DNA extraction methodologies is hindering the ability to compare results between studies and sometimes leading to errant conclusions. The purpose of this article is to highlight the issues related to DNA extraction methods and to suggest minimum standard requirements that should be followed to ensure consistency and reproducibility.
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DNA/isolamento & purificação , Genômica/normas , Microbiota , DNA/normas , Fezes/química , HumanosRESUMO
OBJECTIVE: Obesity is a risk factor for colorectal cancer (CRC), accounting for more than 14% of CRC incidence. Microbial dysbiosis and chronic inflammation are common characteristics in both obesity and CRC. Human and murine studies, together, demonstrate the significant impact of the microbiome in governing energy metabolism and CRC development; yet, little is understood about the contribution of the microbiome to development of obesity-associated CRC as compared to individuals who are not obese. DESIGN: In this study, we conducted a meta-analysis using five publicly available stool and tissue-based 16S rRNA and whole genome sequencing (WGS) data sets of CRC microbiome studies. High-resolution analysis was employed for 16S rRNA data, which allowed us to achieve species-level information to compare with WGS. RESULTS: Characterisation of the confounders between studies, 16S rRNA variable region and sequencing method did not reveal any significant effect on alpha diversity in CRC prediction. Both 16S rRNA and WGS were equally variable in their ability to predict CRC. Results from diversity analysis confirmed lower diversity in obese individuals without CRC; however, no universal differences were found in diversity between obese and non-obese individuals with CRC. When examining taxonomic differences, the probability of being classified as CRC did not change significantly in obese individuals for all taxa tested. However, random forest classification was able to distinguish CRC and non-CRC stool when body mass index was added to the model. CONCLUSION: Overall, microbial dysbiosis was not a significant factor in explaining the higher risk of colon cancer among individuals with obesity.
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BACKGROUND: Lung cancer is the leading cancer diagnosis worldwide and the number one cause of cancer deaths. Exposure to cigarette smoke, the primary risk factor in lung cancer, reduces epithelial barrier integrity and increases susceptibility to infections. Herein, we hypothesize that somatic mutations together with cigarette smoke generate a dysbiotic microbiota that is associated with lung carcinogenesis. Using lung tissue from 33 controls and 143 cancer cases, we conduct 16S ribosomal RNA (rRNA) bacterial gene sequencing, with RNA-sequencing data from lung cancer cases in The Cancer Genome Atlas serving as the validation cohort. RESULTS: Overall, we demonstrate a lower alpha diversity in normal lung as compared to non-tumor adjacent or tumor tissue. In squamous cell carcinoma specifically, a separate group of taxa are identified, in which Acidovorax is enriched in smokers. Acidovorax temporans is identified within tumor sections by fluorescent in situ hybridization and confirmed by two separate 16S rRNA strategies. Further, these taxa, including Acidovorax, exhibit higher abundance among the subset of squamous cell carcinoma cases with TP53 mutations, an association not seen in adenocarcinomas. CONCLUSIONS: The results of this comprehensive study show both microbiome-gene and microbiome-exposure interactions in squamous cell carcinoma lung cancer tissue. Specifically, tumors harboring TP53 mutations, which can impair epithelial function, have a unique bacterial consortium that is higher in relative abundance in smoking-associated tumors of this type. Given the significant need for clinical diagnostic tools in lung cancer, this study may provide novel biomarkers for early detection.
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Neoplasias Pulmonares/genética , Neoplasias Pulmonares/microbiologia , Microbiota/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Biodiversidade , Comamonadaceae/classificação , Comamonadaceae/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Neoplasias de Células Escamosas/genética , Neoplasias de Células Escamosas/microbiologia , Proteobactérias/metabolismo , Reprodutibilidade dos Testes , Fumantes , Proteína Supressora de Tumor p53/metabolismoRESUMO
The microbes residing in the human gut, referred to as the microbiome, are intricately linked to energy homeostasis and subsequently obesity. Integral to the origins of obesity, the microbiome is believed to affect not only health of the human gut but also overall health. This microbiome-obesity association is mediated through the process of energy extraction, metabolism, and cross talk between the brain and the gut microbiome. Host exposures, including diet, that potentially modify genetic predisposition to obesity and affect weight management are reviewed. The higher prevalence of obesity among women and recent evidence linking obesity during pregnancy with offspring health make this topic particularly relevant. Current limitations in microbiome research to address obesity and future advances in this field are described. Applications of this science with respect to applied nursing and overall health care in general are included, with emphasis on the reproductive health of women and their offspring.