scholarly journals The microbiome in PTEN hamartoma tumor syndrome

2018 ◽  
Vol 25 (3) ◽  
pp. 233-243 ◽  
Author(s):  
Victoria Byrd ◽  
Ted Getz ◽  
Roshan Padmanabhan ◽  
Hans Arora ◽  
Charis Eng

Germline PTEN mutations defining PTEN hamartoma tumor syndrome (PHTS) confer heritable predisposition to breast, endometrial, thyroid and other cancers with known age-related risks, but it remains impossible to predict if any individual will develop cancer. In the general population, gut microbial dysbiosis has been linked to cancer, yet is unclear whether these are associated in PHTS patients. In this pilot study, we aimed to characterize microbial composition of stool, urine, and oral wash from 32 PTEN mutation-positive individuals using 16S rRNA gene sequencing. PCoA revealed clustering of the fecal microbiome by cancer history (P = 0.03, R 2 = 0.04). Fecal samples from PHTS cancer patients had relatively more abundant operational taxonomic units (OTUs) from family Rikenellaceae and unclassified members of Clostridia compared to those from non-cancer patients, whereas families Peptostreptococcaceae, Enterobacteriaceae, and Bifidobacteriaceae represented relatively more abundant OTUs among fecal samples from PHTS non-cancer patients. Functional metagenomic prediction revealed enrichment of the folate biosynthesis, genetic information processing and cell growth and death pathways among fecal samples from PHTS cancer patients compared to non-cancer patients. We found no major shifts in overall diversity and no clustering by cancer history among oral wash or urine samples. Our observations suggest the utility of an expanded study to interrogate gut dysbiosis as a potential cancer risk modifier in PHTS patients.

2021 ◽  
Vol 12 ◽  
Author(s):  
Yun Li ◽  
Yuting Cai ◽  
Qian Huang ◽  
Wei Tan ◽  
Bingyan Li ◽  
...  

PurposeChoroidal neovascularization (CNV) is the defining feature of neovascular age-related macular degeneration (nAMD). Gut microbiota might be deeply involved in the pathogenesis of nAMD. This study aimed to reveal the roles of the gut microbiome and fecal metabolome in a mouse model of laser-induced CNV.MethodsThe feces of C57BL/6J mice with or without laser-induced CNV were collected. Multi-omics analyses, including 16S rRNA gene sequencing and untargeted metabolomics, were conducted to analyze the changes in the gut microbial composition and the fecal metabolomic profiles in CNV mice.ResultsThe gut microbiota was significantly altered in CNV mice. The abundance of Candidatus_Saccharimonas was significantly upregulated in the feces of CNV mice, while 16 genera, including Prevotellaceae_NK3B31_group, Candidatus_Soleaferrea, and Truepera, were significantly more abundant in the controls than in the CNV group. Fecal metabolomics identified 73 altered metabolites (including 52 strongly significantly altered metabolites) in CNV mice compared to control mice. Correlation analysis indicated significant correlations between the altered fecal metabolites and gut microbiota genera, such as Lachnospiraceae_UCG-001 and Candidatus_Saccharimonas. Moreover, KEGG analysis revealed six pathways associated with these altered metabolites, such as the ABC transporter, primary bile acid biosynthesis and steroid hormone biosynthesis pathways.ConclusionThe study identified an altered fecal microbiome and metabolome in a CNV mouse model. The altered microbes, metabolites and the involved pathways might be associated with the pathogenesis of nAMD.


Author(s):  
Ravichandra Vemuri ◽  
Chrissy Sherrill ◽  
Matthew A Davis ◽  
Kylie Kavanagh

Abstract Age-related changes in gut microbiome impact host health. The interactive relationship between the microbiome and physiological systems in an aged body system remains to be clearly defined, particularly in the context of inflammation. Therefore, we aimed to evaluate systemic inflammation, microbial translocation (MT), and differences between fecal and mucosal microbiomes. Ascending colon mucosal biopsies, fecal samples, and blood samples from healthy young and old female vervet monkeys were collected for 16S rRNA gene sequencing, MT, and cytokine analyses, respectively. To demonstrate microbial co-occurrence patterns, we used Kendall’s tau correlation measure of interactions between microbes. We found elevated levels of plasma LBP-1, MCP-1, and CRP in old monkeys, indicative of higher MT and systemic inflammation. Microbiome analysis revealed significant differences specific to age. At the phylum level, abundances of pathobionts such as Proteobacteria were increased in the mucosa of old monkeys. At the family level, Helicobacteriaceae was highly abundant in mucosal samples (old); in contrast, Ruminococcaceae were higher in the fecal samples of old monkeys. We found significantly lower Firmicutes:Bacteroidetes ratio and lower abundance of butyrate-producing microbes in old monkeys, consistent with less healthy profiles. Microbial community co-occurrence analysis on mucosal samples revealed 13 nodes and 41 associations in the young monkeys, but only 12 nodes and 21 associations in the old monkeys. Our findings provide novel insights into systemic inflammation and gut microbial interactions, highlight the importance of the mucosal niche, and facilitate further understanding of the decline in the stability of the microbial community with aging.


Author(s):  
Feilong Deng ◽  
Maryanna McClure ◽  
Rick Rorie ◽  
Xiaofan Wang ◽  
Jianmin Chai ◽  
...  

Abstract Background The greatest impact on profitability of a commercial beef operation is reproduction. However, in beef heifers, little is known about the vaginal and fecal microbiota with respect to their relationship with fertility. To this end, we followed heifers through gestation to examine the dynamics of vaginal and fecal microbial composition throughout pregnancy. Results Heifers were exposed to an estrus synchronization protocol, observed over a 12-day period, artificially inseminated 12 h to 18 h after observed estrus, and subsequently exposed to bulls for a 50-day breeding season. Vaginal samples were taken at pre-breeding (n = 72), during the first (n = 72), and second trimester (n = 72) for all individuals, and third trimester for individuals with confirmed pregnancies (n = 56). Fecal samples were taken at pre-breeding (n = 32) and during the first trimester (n = 32), including bred and open individuals. Next generation sequencing of the V4 region of the16S rRNA gene via the Illumina MiSeq platform was applied to all samples. Shannon indices and the number of observed bacterial features were the same in fecal samples. However, significant differences in vaginal microbiome diversity between gestation stages were observed. No differences in beta-diversity were detected in vaginal or fecal samples regarding pregnancy status, but such differences were seen with fecal microbiome over time. Random Forest was developed to identify predictors of pregnancy status in vaginal (e.g., Histophilus, Clostridiaceae, Campylobacter) and fecal (e.g., Bacteroidales, Dorea) samples. Conclusions Our study shows that bovine vaginal and fecal microbiome could be used as biomarkers of bovine reproduction. Further experiments are needed to validate these biomarkers and to examine their roles in a female’s ability to establish pregnancy.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jian Chen ◽  
Ai Jin ◽  
Lei Huang ◽  
Yan Zhao ◽  
Yuwen Li ◽  
...  

Comprehensive microbial analysis has revealed that the lung harbors a complex variety of microbiota, and although the dynamic distribution of the lung microbiota in mice and laying hens of different ages is well established, this distribution has not been clarified in broilers of different ages. Here, we performed 16S rRNA gene sequencing of lung lavage fluid from broilers at 3 (3D), 7 (7D), 14 (14D), 21 (21D), and 35 (35D) days of age to evaluate changes in the composition of their lung microbiota. Upon examination of the composition and function of the broiler lung microbiota, we found that their maturation increased significantly with age. Specifically, the microbiota composition was similar between 7 and 14D and between 21 and 35D. The relative abundance of aerobic bacteria in the broiler lungs gradually increased as the broilers developed, whereas the relative abundance of potentially pathogenic bacteria reached its highest level at 3D. The relative abundance of predicted functions in microbiota was very similar among 3, 7, and 14D, whereas the Glycan Biosynthesis and Metabolism pathway in microbiota was enriched at 21D. These findings suggest that these metabolic pathways play critical roles in shaping broiler microbiota at these age stages. In addition, short-term external ammonia stimulation significantly increased lung inflammation but did not significantly affect the lung microbiota. Taken together, these data reveal the dynamics of age-related changes in the microbiota of broiler lungs and the stability (the significant variation in the microbial composition) of these microbial communities in response to short-term ammonia stress. These findings provide new insights into the development of broiler lung microbiota and serve as a reference for subsequent studies to evaluate disease prevention in broilers subjected to large-scale breeding.


2019 ◽  
Vol 20 (6) ◽  
pp. 1430 ◽  
Author(s):  
Laetitia Cortes ◽  
Harm Wopereis ◽  
Aude Tartiere ◽  
Julie Piquenot ◽  
Joost Gouw ◽  
...  

A metaproteomic analysis was conducted on the fecal microbiome of eight infants to characterize global protein and pathway expression. Although mass spectrometry-based proteomics is now a routine tool, analysis of the microbiome presents specific technical challenges, including the complexity and dynamic range of member taxa, the need for well-annotated metagenomic databases, and high inter-protein sequence redundancy and similarity. In this study, an approach was developed for assessment of biological phenotype and metabolic status, as a functional complement to DNA sequence analysis. Fecal samples were prepared and analysed by tandem mass spectrometry and a homology-based meta-clustering strategy was used to combine peptides from multiple species into representative proteins. In total, 15,250 unique peptides were sequenced and assigned to 2154 metaclusters, which were then assigned to pathways and functional groups. Differences were noted in several pathways, consistent with the dominant genera observed in different subjects. Although this study was not powered to draw conclusions from the comparisons, the results obtained demonstrate the applicability of this approach and provide the methods needed for performing semi-quantitative comparisons of human fecal microbiome composition, physiology and metabolism, as well as a more detailed assessment of microbial composition in comparison to 16S rRNA gene sequencing.


Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 254
Author(s):  
Ying Wang ◽  
Jianqing Zhu ◽  
Jie Fang ◽  
Li Shen ◽  
Shuojia Ma ◽  
...  

We characterized the gut microbial composition and relative abundance of gut bacteria in the larvae and adults of Pieris canidia by 16S rRNA gene sequencing. The gut microbiota structure was similar across the life stages and sexes. The comparative functional analysis on P. canidia bacterial communities with PICRUSt showed the enrichment of several pathways including those for energy metabolism, immune system, digestive system, xenobiotics biodegradation, transport, cell growth and death. The parameters often used as a proxy of insect fitness (development time, pupation rate, emergence rate, adult survival rate and weight of 5th instars larvae) showed a significant difference between treatment group and untreated group and point to potential fitness advantages with the gut microbiomes in P. canidia. These data provide an overall view of the bacterial community across the life stages and sexes in P. canidia.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Esteban Góngora ◽  
Kyle H. Elliott ◽  
Lyle Whyte

AbstractThe role of the gut microbiome is increasingly being recognized by health scientists and veterinarians, yet its role in wild animals remains understudied. Variations in the gut microbiome could be the result of differential diets among individuals, such as variation between sexes, across seasons, or across reproductive stages. We evaluated the hypothesis that diet alters the avian gut microbiome using stable isotope analysis (SIA) and 16S rRNA gene sequencing. We present the first description of the thick-billed murre (Uria lomvia) fecal microbiome. The murre microbiome was dominated by bacteria from the genus Catellicoccus, ubiquitous in the guts of many seabirds. Microbiome variation was explained by murre diet in terms of proportion of littoral carbon, trophic position, and sulfur isotopes, especially for the classes Actinobacteria, Bacilli, Bacteroidia, Clostridia, Alphaproteobacteria, and Gammaproteobacteria. We also observed differences in the abundance of bacterial genera such as Catellicoccus and Cetobacterium between sexes and reproductive stages. These results are in accordance with behavioural observations of changes in diet between sexes and across the reproductive season. We concluded that the observed variation in the gut microbiome may be caused by individual prey specialization and may also be reinforced by sexual and reproductive stage differences in diet.


2017 ◽  
Vol 8 (5) ◽  
pp. 681-695 ◽  
Author(s):  
J.S.Y. Low ◽  
S.-E. Soh ◽  
Y.K. Lee ◽  
K.Y.C. Kwek ◽  
J.D. Holbrook ◽  
...  

Several studies have reported that intestinal microbial colonisation patterns differ between non-allergic and allergic infants. However, the microbial signature underlying the pathogenesis of allergies remains unclear. We aim to gain insight into the development of the intestinal microbiota of healthy infants and infants who develop allergy in early life, and identify potential microbiota biomarkers of later allergic disease. Using a case-control design in a Chinese sub-cohort of a Singaporean birth cohort (GUSTO), we utilised 16S rRNA gene sequencing to assess intestinal microbial composition and diversity of 21 allergic and 18 healthy infants at 3 weeks, 3 months and 6 months of age, and correlated the microbiota with allergy at ages 18 and 36 months. Pronounced differences in intestinal microbiota composition between allergic and healthy infants were observed at 3 months of age. The intestine of healthy infants was colonised with higher abundance of commensal Bifidobacterium. Conversely, Klebsiella, an opportunistic pathogen, was significantly enriched in the allergic infants. Interestingly, infants with a high Klebsiella/Bifidobacterium (K/B) ratio (above the population median K/B ratio) at age 3 months had an odds ratio of developing allergy by 3 years of age of 9.00 (95% confidence interval 1.46-55.50) compared to those with low K/B ratio. This study demonstrated a relationship between the ratio of genera Klebsiella and Bifidobacterium during early infancy and development of paediatric allergy in childhood. Our study postulates that an elevated K/B ratio in early infancy could be a potential indicator of an increased risk of allergy development. This line of research might enable future intervention strategies in early life to prevent or treat allergy. Our study provides new insights into microbial signatures associated with childhood allergy, in particular, suggests that an elevated K/B ratio could be a potential early-life microbiota biomarker of allergic disease.


2022 ◽  
Vol 8 ◽  
Author(s):  
Weilan Wang ◽  
Jodi E. Nettleton ◽  
Michael G. Gänzle ◽  
Raylene A. Reimer

To identify possible mechanisms by which maternal consumption of non-nutritive sweeteners increases obesity risk in offspring, we reconstructed the major alterations in the cecal microbiome of 3-week-old offspring of obese dams consuming high fat/sucrose (HFS) diet with or without aspartame (5–7 mg/kg/day) or stevia (2–3 mg/kg/day) by shotgun metagenomic sequencing (n = 36). High throughput 16S rRNA gene sequencing (n = 105) was performed for dams, 3- and 18-week-old offspring. Maternal consumption of sweeteners altered cecal microbial composition and metabolism of propionate/lactate in their offspring. Offspring daily body weight gain, liver weight and body fat were positively correlated to the relative abundance of key microbes and enzymes involved in succinate/propionate production while negatively correlated to that of lactose degradation and lactate production. The altered propionate/lactate production in the cecum of weanlings from aspartame and stevia consuming dams implicates an altered ratio of dietary carbohydrate digestion, mainly lactose, in the small intestine vs. microbial fermentation in the large intestine. The reconstructed microbiome alterations could explain increased offspring body weight and body fat. This study demonstrates that intense sweet tastants have a lasting and intergenerational effect on gut microbiota, microbial metabolites and host health.


Author(s):  
Shiju Xiao ◽  
Guangzhong Zhang ◽  
Chunyan Jiang ◽  
Xin Liu ◽  
Xiaoxu Wang ◽  
...  

BackgroundIncreasing evidence has shown that alterations in the intestinal microbiota play an important role in the pathogenesis of psoriasis. The existing relevant studies focus on 16S rRNA gene sequencing, but in-depth research on gene functions and comprehensive identification of microbiota is lacking.ObjectivesTo comprehensively identify characteristic gut microbial compositions, genetic functions and relative metabolites of patients with psoriasis and to reveal the potential pathogenesis of psoriasis.MethodsDNA was extracted from the faecal microbiota of 30 psoriatic patients and 15 healthy subjects, and metagenomics sequencing and bioinformatic analyses were performed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database, cluster of orthologous groups (COG) annotations, and metabolic analyses were used to indicate relative target genes and pathways to reveal the pathogenesis of psoriasis.ResultsCompared with healthy individuals, the gut microbiota of psoriasis patients displayed an alteration in microbial taxa distribution, but no significant difference in microbial diversity. A distinct gut microbial composition in patients with psoriasis was observed, with an increased abundance of the phyla Firmicutes, Actinobacteria and Verrucomicrobia and genera Faecalibacterium, Bacteroides, Bifidobacterium, Megamonas and Roseburia and a decreased abundance of the phyla Bacteroidetes, Euryarchaeota and Proteobacteria and genera Prevotella, Alistipes, and Eubacterium. A total of 134 COGs were predicted with functional analysis, and 15 KEGG pathways, including lipopolysaccharide (LPS) biosynthesis, WNT signaling, apoptosis, bacterial secretion system, and phosphotransferase system, were significantly enriched in psoriasis patients. Five metabolites, hydrogen sulfide (H2S), isovalerate, isobutyrate, hyaluronan and hemicellulose, were significantly dysregulated in the psoriatic cohort. The dysbiosis of gut microbiota, enriched pathways and dysregulated metabolites are relevant to immune and inflammatory response, apoptosis, the vascular endothelial growth factor (VEGF) signaling pathway, gut-brain axis and brain-skin axis that play important roles in the pathogenesis of psoriasis.ConclusionsA clear dysbiosis was displayed in the gut microbiota profile, genetic functions and relative metabolites of psoriasis patients. This study is beneficial for further understanding the inflammatory pathogenesis of psoriasis and could be used to develop microbiome-based predictions and therapeutic approaches.


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