Increasing evidence suggests that the composition of the human gut microbiome is important in the etiology of human diseases; however, the personal factors that influence the gut microbiome ...composition are poorly characterized. Animal models point to sex hormone-related differentials in microbiome composition. In this study, we investigated the relationship of sex, body mass index (BMI) and dietary fiber intake with the gut microbiome in 82 humans. We sequenced fecal 16S rRNA genes by 454 FLX technology, then clustered and classified the reads to microbial genomes using the QIIME pipeline. Relationships of sex, BMI, and fiber intake with overall gut microbiome composition and specific taxon abundances were assessed by permutational MANOVA and multivariate logistic regression, respectively. We found that sex was associated with the gut microbiome composition overall (p=0.001). The gut microbiome in women was characterized by a lower abundance of Bacteroidetes (p=0.03). BMI (>25 kg/m2 vs. <25 kg/m2) was associated with the gut microbiome composition overall (p=0.05), and this relationship was strong in women (p=0.03) but not in men (p=0.29). Fiber from beans and from fruits and vegetables were associated, respectively, with greater abundance of Actinobacteria (p=0.006 and false discovery rate adjusted q=0.05) and Clostridia (p=0.009 and false discovery rate adjusted q=0.09). Our findings suggest that sex, BMI, and dietary fiber contribute to shaping the gut microbiome in humans. Better understanding of these relationships may have significant implications for gastrointestinal health and disease prevention.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The human microbiome contributes metabolic functions, protects against pathogens, educates the immune system, and through these basic functions, directly or indirectly, affects most of our ...physiologic functions. Here, we consider the human microbiome and its relationship to several major noncommunicable human conditions, including orodigestive tract cancers, neurologic diseases, diabetes, and obesity. We also highlight the scope of contextual macroenvironmental factors (toxicological and chemical environment, built environment, and socioeconomic environment) and individual microenvironmental factors (smoking, alcohol, and diet) that may push the microbiota toward less healthy or more healthy conditions, influencing the development of these diseases. Last, we highlight current uncertainties and challenges in the study of environmental influences on the human microbiome and implications for understanding noncommunicable disease, suggesting a research agenda to strengthen the scientific evidence base.
Early-onset colorectal cancer (CRC) is increasing in the USA despite rapid declines in older ages. Similar patterns are reported in Australia and Canada, but a comprehensive global analysis of ...contemporary data is lacking.
We extracted long-term data from Cancer Incidence in Five Continents and supplemental sources to report on worldwide CRC incidence rates and trends by age (20-49 years and ≥50 years) through diagnosis year 2012 or beyond (Australia, Finland, New Zealand, Norway, Sweden, USA).
During 2008-2012, age-standardised CRC incidence rates in adults <50 ranged from 3.5 per 100 000 (95% CI 3.2 to 3.9) in India (Chennai) to 12.9 (95% CI 12.6 to 13.3) in Korea. During the most recent decade of available data, incidence in adults <50 was stable in 14 of 36 countries; declined in Austria, Italy and Lithuania; and increased in 19 countries, nine of which had stable or declining trends in older adults (Australia, Canada, Denmark, Germany, New Zealand, Slovenia, Sweden, UK and USA). In Cyprus, Netherlands and Norway, inclines in incidence in young adults were twice as rapid as those in older adults (eg, Norway average annual per cent change (AAPC), 1.9 (95% CI 1.4 to 2.5) vs 0.5 (95% CI 0.3 to 0.7)). Among most high-income countries with long-term data, the uptick in early-onset disease began in the mid-1990s. The steepest increases in young adults were in Korea (AAPC, 4.2 (95% CI 3.4 to 5.0)) and New Zealand (AAPC, 4.0 (95% CI 2.1 to 6.0)).
CRC incidence increased exclusively in young adults in nine high-income countries spanning three continents, potentially signalling changes in early-life exposures that influence large bowel carcinogenesis.
Periodontitis, the progressive loss of the alveolar bone around the teeth and the major cause of tooth loss in adults, is due to oral microorganisms, including Porphyromonas gingivalis. Periodontitis ...is associated with a local overly aggressive immune response and a spectrum of systemic effects, but the role of this condition in orodigestive cancers is unclear. We prospectively examined clinically ascertained periodontitis (N = 12,605) and serum IgG immune response to P.gingivalis (N = 7852) in relation to orodigestive cancer mortality among men and women in the National Health and Nutrition Examination Survey III. A detailed oral health exam was conducted from 1988 to 1994 in survey Phases I and II, whereas serum IgG for P.gingivalis was measured from 1991 to 1994 in Phase II only. One hundred and five orodigestive cancer deaths were ascertained through 31 December 2006. Periodontitis (moderate or severe) was associated with increased orodigestive cancer mortality relative risks (RR) = 2.28, 95% confidence interval (CI) = 1.17-4.45; mortality risks also increased with increasing severity of periodontal disease (P trend = 0.01). Periodontitis-associated mortality was in excess for colorectal (RR = 3.58; 95% CI = 1.15-11.16) and possibly for pancreatic cancer (RR = 4.56; 95% CI = 0.93-22.29). Greater serum P.gingivalis IgG tended to be associated overall with increased orodigestive cancer mortality (P trend = 0.06); P.gingivalis-associated excess orodigestive mortality was also found for healthy subjects not exhibiting overt periodontal disease (RR = 2.25; 95% CI = 1.23-4.14). Orodigestive cancer mortality is related to periodontitis and to the periodontal pathogen, P.gingivalis, independent of periodontal disease. Porphyromonas gingivalis is a biomarker for microbe-associated risk of death due to orodigestive cancer.
Abstract
Background
Ambient air pollution is a modifiable risk factor for cardiovascular disease, yet uncertainty remains about the size of risks at lower levels of fine particulate matter (PM2.5) ...exposure which now occur in the USA and elsewhere.
Methods
We investigated the relationship of ambient PM2.5 exposure with cause-specific cardiovascular disease mortality in 565 477 men and women, aged 50 to 71 years, from the National Institutes of Health-AARP Diet and Health Study. During 7.5 x 106 person-years of follow up, 41 286 cardiovascular disease deaths, including 23 328 ischaemic heart disease (IHD) and 5894 stroke deaths, were ascertained using the National Death Index. PM2.5 was estimated using a hybrid land use regression (LUR) geostatistical model. Multivariate Cox regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CI).
Results
Each increase of 10 μg/m3 PM2.5 (overall range, 2.9–28.0 μg/m3) was associated, in fully adjusted models, with a 16% increase in mortality from ischaemic heart disease hazard ratio (HR) 1.16; 95% CI 1.09-1.22 and a 14% increase in mortality from stroke (HR 1.14; CI 1.02-1.27). Compared with PM2.5 exposure <8 μg/m3 (referent), risks for CVD were increased in relation to PM2.5 exposures in the range of 8–12 μg/m3 (CVD: HR 1.04; 95% CI 1.00-1.08), in the range 12–20 μg/m3 (CVD: HR 1.08; 95% CI 1.03-1.13) and in the range 20+ μg/m3 (CVD: HR 1.19; 95% CI 1.10-1.28). Results were robust to alternative approaches to PM2.5 exposure assessment and statistical analysis.
Conclusions
Long-term exposure to fine particulate air pollution is associated with ischaemic heart disease and stroke mortality, with excess risks occurring in the range of and below the present US long-term standard for ambient exposure to PM2.5 (12 µg/m3), indicating the need for continued improvements in air pollution abatement for CVD prevention.
Population-based epidemiologic studies can provide important insight regarding the role of the microbiome in human health and disease. Buccal cells samples using commercial mouthwash have been ...obtained in large prospective cohorts for the purpose of studying human genomic DNA. We aimed to better understand if these mouthwash samples are also a valid resource for the study of the oral microbiome. We collected one saliva sample and one Scope mouthwash sample from 10 healthy subjects. Bacterial 16S rRNA genes from both types of samples were amplified, sequenced, and assigned to bacterial taxa. We comprehensively compared these paired samples for bacterial community composition and individual taxonomic abundance. We found that mouthwash samples yielded similar amount of bacterial DNA as saliva samples (p from Student's t-test for paired samples = 0.92). Additionally, the paired samples had similar within sample diversity (p from = 0.33 for richness, and p = 0.51 for Shannon index), and clustered as pairs for diversity when analyzed by unsupervised hierarchical cluster analysis. No significant difference was found in the paired samples with respect to the taxonomic abundance of major bacterial phyla, Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria, and Actinobacteria (FDR adjusted q values from Wilcoxin signed-rank test = 0.15, 0.15, 0.87, 1.00 and 0.15, respectively), and all identified genera, including genus Streptococcus (q = 0.21), Prevotella (q = 0.25), Neisseria (q = 0.37), Veillonella (q = 0.73), Fusobacterium (q = 0.19), and Porphyromonas (q = 0.60). These results show that mouthwash samples perform similarly to saliva samples for analysis of the oral microbiome. Mouthwash samples collected originally for analysis of human DNA are also a resource suitable for human microbiome research.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Investigation of microbe-metabolite relationships in the gut is needed to understand and potentially reduce colorectal cancer (CRC) risk.
Microbiota and metabolomics profiling were performed on ...lyophilized feces from 42 CRC cases and 89 matched controls. Multivariable logistic regression was used to identify statistically independent associations with CRC. First principal coordinate-component pair (PCo1-PC1) and false discovery rate (0.05)-corrected P-values were calculated for 116,000 Pearson correlations between 530 metabolites and 220 microbes in a sex*case/control meta-analysis.
Overall microbe-metabolite PCo1-PC1 was more strongly correlated in cases than in controls (Rho 0.606 vs 0.201, P = 0.01). CRC was independently associated with lower levels of Clostridia, Lachnospiraceae, p-aminobenzoate and conjugated linoleate, and with higher levels of Fusobacterium, Porphyromonas, p-hydroxy-benzaldehyde, and palmitoyl-sphingomyelin. Through postulated effects on cell shedding (palmitoyl-sphingomyelin), inflammation (conjugated linoleate), and innate immunity (p-aminobenzoate), metabolites mediated the CRC association with Fusobacterium and Porphyromonas by 29% and 34%, respectively. Overall, palmitoyl-sphingomyelin correlated directly with abundances of Enterobacteriaceae (Gammaproteobacteria), three Actinobacteria and five Firmicutes. Only Parabacteroides correlated inversely with palmitoyl-sphingomyelin. Other lipids correlated inversely with Alcaligenaceae (Betaproteobacteria). Six Bonferroni-significant correlations were found, including low indolepropionate and threnoylvaline with Actinobacteria and high erythronate and an uncharacterized metabolite with Enterobacteriaceae.
Feces from CRC cases had very strong microbe-metabolite correlations that were predominated by Enterobacteriaceae and Actinobacteria. Metabolites mediated a direct CRC association with Fusobacterium and Porphyromonas, but not an inverse association with Clostridia and Lachnospiraceae. This study identifies complex microbe-metabolite networks that may provide insights on neoplasia and targets for intervention.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human microbiota have many functions that could contribute to cancer initiation and/or progression at local sites, yet the relation of the lung microbiota to lung cancer prognosis has not been ...studied.
In a pilot study, 16S rRNA gene sequencing was performed on paired lung tumor and remote normal samples from the same lobe/segment in 19 patients with non-small cell lung cancer (NSCLC). We explored associations of tumor or normal tissue microbiome diversity and composition with recurrence-free (RFS) and disease-free survival (DFS), and compared microbiome diversity and composition between paired tumor and normal samples.
Higher richness and diversity in normal tissue were associated with reduced RFS (richness
= 0.08, Shannon index
= 0.03) and DFS (richness
= 0.03, Shannon index
= 0.02), as was normal tissue overall microbiome composition (Bray-Curtis
= 0.09 for RFS and
= 0.02 for DFS). In normal tissue, greater abundance of family Koribacteraceae was associated with increased RFS and DFS, whereas greater abundance of families Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae were associated with reduced RFS or DFS (
< 0.05). Tumor tissue diversity and overall composition were not associated with RFS or DFS. Tumor tissue had lower richness and diversity (
≤ 0.0001) than paired normal tissue, though overall microbiome composition did not differ between the paired samples.
We demonstrate, for the first time, a potential relationship between the normal lung microbiota and lung cancer prognosis, which requires confirmation in a larger study.
Definition of bacterial biomarkers of prognosis may lead to improved survival outcomes for patients with lung cancer.
We tested the hypothesis that an altered community of gut microbes is associated with risk of colorectal cancer (CRC) in a study of 47 CRC case subjects and 94 control subjects. 16S rRNA genes in ...fecal bacterial DNA were amplified by universal primers, sequenced by 454 FLX technology, and aligned for taxonomic classification to microbial genomes using the QIIME pipeline. Taxonomic differences were confirmed with quantitative polymerase chain reaction and adjusted for false discovery rate. All statistical tests were two-sided. From 794217 16S rRNA gene sequences, we found that CRC case subjects had decreased overall microbial community diversity (P = .02). In taxonomy-based analyses, lower relative abundance of Clostridia (68.6% vs 77.8%) and increased carriage of Fusobacterium (multivariable odds ratio OR = 4.11; 95% confidence interval CI = 1.62 to 10.47) and Porphyromonas (OR = 5.17; 95% CI = 1.75 to 15.25) were found in case subjects compared with control subjects. Because of the potentially modifiable nature of the gut bacteria, our findings may have implications for CRC prevention.
A history of periodontal disease and the presence of circulating antibodies to selected oral pathogens have been associated with increased risk of pancreatic cancer; however, direct relationships of ...oral microbes with pancreatic cancer have not been evaluated in prospective studies. We examine the relationship of oral microbiota with subsequent risk of pancreatic cancer in a large nested case-control study.
We selected 361 incident adenocarcinoma of pancreas and 371 matched controls from two prospective cohort studies, the American Cancer Society Cancer Prevention Study II and the National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. From pre-diagnostic oral wash samples, we characterised the composition of the oral microbiota using bacterial 16S ribosomal RNA (16S rRNA) gene sequencing. The associations between oral microbiota and risk of pancreatic cancer, controlling for the random effect of cohorts and other covariates, were examined using traditional and L1-penalised least absolute shrinkage and selection operator logistic regression.
Carriage of oral pathogens,
and
, were associated with higher risk of pancreatic cancer (adjusted OR for presence vs absence=1.60 and 95% CI 1.15 to 2.22; OR=2.20 and 95% CI 1.16 to 4.18, respectively). Phylum
and its genus
were associated with decreased pancreatic cancer risk (OR per per cent increase of relative abundance=0.94 and 95% CI 0.89 to 0.99; OR=0.87 and 95% CI 0.79 to 0.95, respectively). Risks related to these phylotypes remained after exclusion of cases that developed within 2 years of sample collection, reducing the likelihood of reverse causation in this prospective study.
This study provides supportive evidence that oral microbiota may play a role in the aetiology of pancreatic cancer.
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