Colorectal Cancer-Associated Microbiome Patterns and Signatures

The gut microbiome is dynamic and shaped by diet, age, geography, and environment. The disruption of normal gut microbiota (dysbiosis) is closely related to colorectal cancer (CRC) risk and progression. To better identify and characterize CRC-associated dysbiosis, we collected six independent cohorts with matched normal pairs (when available) for comparison and exploration of the microbiota and their interactions with the host. Comparing the microbial community compositions between cancerous and adjacent noncancerous tissues, we found that more microbes were depleted than enriched in tumors. Despite taxonomic variations among cohorts, consistent depletion of normal microbiota (members of Clostridia and Bacteroidia) and significant enrichment of oral-originated pathogens (such as Fusobacterium nucleatum and Parvimonas micra) were observed in CRC compared to normal tissues. Sets of hub and hub-connecting microbes were subsequently identified to infer microbe-microbe interaction networks in CRC. Furthermore, biclustering was used for identifying coherent patterns between patients and microbes. Two patient-microbe interaction patterns, named P0 and P1, can be consistently identified among the investigated six CRC cohorts. Characterization of the microbial community composition of the two patterns revealed that patients in P0 and P1 differed significantly in microbial alpha and beta diversity, and CRC‐associated microbiota changes consist of continuous populations of widespread taxa rather than discrete enterotypes. In contrast to the P0, the patients in P1 have reduced microbial alpha diversity compared to the adjacent normal tissues, and P1 possesses more oral-related pathogens than P0 and controls. Collectively, our study investigated the CRC-associated microbiome changes, and identified reproducible microbial signatures across multiple independent cohorts. More importantly, we revealed that the CRC heterogeneity can be partially attributed to the variety and compositional differences of microbes and their interactions to humans.

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AB1232 ORAL DYSBIOSIS REFLECTS THE IMMUNOLOGICAL ALTERATION OF RA REGARDING TO ACPA AND HLA DRB1*SE: NAGASAKI ISLAND STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5147 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1907.2-1907

Author(s):

Y. Tsuji ◽

M. Tamai ◽

S. Morimoto ◽

D. Sasaki ◽

M. Nagayoshi ◽

...

Keyword(s):

Beta Diversity ◽

Healthy Subjects ◽

Microbial Community Composition ◽

Alpha Diversity ◽

Enzyme Linked Immunosorbent Assay ◽

Rrna Gene ◽

Oral Microbiota ◽

Unifrac Distance ◽

Alpha And Beta Diversity ◽

The Difference

Background:Anti-citrullinated protein antibody (ACPA) production is observed in several organs even prior to the onset of rheumatoid arthritis (RA), and oral mucosa is considered to be one of the important tissues. The presence of HLA-DRB1*SE closely associates with ACPA production. Saliva is considered to reflect the oral microbiota including periodontal disease. Alteration of oral microbiota of RA becomes to be normalized by DMARDs treatment, however, the interaction of HLA-DRB1*SE, ACPA and oral microbiota of RA patients remains to be elucidated.Objectives:The Nagasaki Island Study, which had started in 2014 collaborating with Goto City, is intended for research of the preclinical stage of RA, including ACPA/HLA genotype screening and ultrasound and magnetic resonance imaging examinations in high-risk subjects. Using the samples accumulated in this cohort, we have tried to investigate the difference of oral microbiota among RA patients and healthy subjects regarding to ACPA and HLA-DRB1*SE.Methods:Blood and salivary samples were obtained from 1422 subjects out of 4276 who have participated in the Nagasaki Island Study from 2016 to 2018. ACPA positivity was 1.7 % in total. Some of RA patients resided in Goto City participated in the Nagasaki Island Study. At this point, we selected 291 subjects, who were ACPA positive non-RA healthy subjects (n=22) and patients with RA (n=33, 11 subjects were ACPA positive and 22 ACPA negative respectively) as the case, age and gender matched ACPA negative non-RA healthy subjects (n=236) as the control. ACPA was measured by an enzyme-linked immunosorbent assay, and HLA genotyping was quantified by next-generation sequencing (Ref.1). The operational taxonomic unit (OUT) analysis using 16S rRNA gene sequencing were performed. The richness of microbial diversity within-subject (alpha diversity) was scaled via Shannon entropy. The dissimilarity between microbial community composition was calculated using Bray-Curtis distance as a scale, and differences between groups (beta diversity) were tested by permutational multivariate analysis of variance (PERMANOVA). In addition, UniFrac distance calculated in consideration of the distance on the phylogenetic tree were performed.Results:Median age 70 y.o., % Female 58.8 %. Among RA and non-RA subjects, not alpha diversity but beta diversity was statistically significance (p=0.022, small in RA). In RA subjects, both alpha and beta diversity is small (p<0.0001), especially significant in ACPA positive RA (Figure 1). Amongt RA subjects, presence of HLA-DRB1*SE did not show the difference but the tendency of being small of alpha diversity (p=0.29).Conclusion:Our study has suggested for the first time the association of oral microbiota alteration with the presence of ACPA and HLA-DRB1*SE. Oral dysbiosis may reflect the immunological status of patients with RA.References:[1]Kawaguchi S, et al. Methods Mol Biol 2018;1802: 22Disclosure of Interests:None declared

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Spatial and Annual Variation in Microbial Abundance, Community Composition, and Diversity Associated With Alpine Surface Snow

Frontiers in Microbiology ◽

10.3389/fmicb.2021.781904 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lucas Fillinger ◽

Kerstin Hürkamp ◽

Christine Stumpp ◽

Nina Weber ◽

Dominik Forster ◽

...

Keyword(s):

Climate Change ◽

Microbial Community ◽

Community Composition ◽

Microbial Community Composition ◽

Alpha Diversity ◽

Community Diversity ◽

Taxon Richness ◽

European Alps ◽

Prokaryotic Cell ◽

Surface Snow

Understanding microbial community dynamics in the alpine cryosphere is an important step toward assessing climate change impacts on these fragile ecosystems and meltwater-fed environments downstream. In this study, we analyzed microbial community composition, variation in community alpha and beta diversity, and the number of prokaryotic cells and virus-like particles (VLP) in seasonal snowpack from two consecutive years at three high altitude mountain summits along a longitudinal transect across the European Alps. Numbers of prokaryotic cells and VLP both ranged around 104 and 105 per mL of snow meltwater on average, with variation generally within one order of magnitude between sites and years. VLP-to-prokaryotic cell ratios spanned two orders of magnitude, with median values close to 1, and little variation between sites and years in the majority of cases. Estimates of microbial community alpha diversity inferred from Hill numbers revealed low contributions of common and abundant microbial taxa to the total taxon richness, and thus low community evenness. Similar to prokaryotic cell and VLP numbers, differences in alpha diversity between years and sites were generally relatively modest. In contrast, community composition displayed strong variation between sites and especially between years. Analyses of taxonomic and phylogenetic community composition showed that differences between sites within years were mainly characterized by changes in abundances of microbial taxa from similar phylogenetic clades, whereas shifts between years were due to significant phylogenetic turnover. Our findings on the spatiotemporal dynamics and magnitude of variation of microbial abundances, community diversity, and composition in surface snow may help define baseline levels to assess future impacts of climate change on the alpine cryosphere.

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PSI-10 Establishing a foundation to harvest the potential of the microbiome in poultry production

Journal of Animal Science ◽

10.1093/jas/skz258.594 ◽

2019 ◽

Vol 97 (Supplement_3) ◽

pp. 293-294

Author(s):

Camila S Marcolla ◽

Benjamin Willing

Keyword(s):

Microbial Community ◽

Gut Microbiota ◽

Community Composition ◽

Relative Abundance ◽

Microbial Community Composition ◽

Alpha Diversity ◽

Poultry Production ◽

Microbiota Composition ◽

Microbial Composition ◽

The Impact

Abstract This study aimed to characterize poultry microbiota composition in commercial farms using 16S rRNA sequencing. Animals raised in sanitized environments have lower survival rates when facing pathogenic challenges compared to animals naturally exposed to commensal organisms. We hypothesized that intensive rearing practices inadvertently impair chicken exposure to microbes and the establishment of a balanced gut microbiota. We compared gut microbiota composition of broilers (n = 78) and layers (n = 20) from different systems, including commercial intensive farms with and without in-feed antibiotics, organic free-range farms, backyard-raised chickens and chickens in an experimental farm. Microbial community composition of conventionally raised broilers was significantly different from antibiotic-free broilers (P = 0.012), from broilers raised outdoors (P = 0.048) and in an experimental farm (P = 0.006) (Fig1). Significant community composition differences were observed between antibiotic-fed and antibiotic-free chickens (Fig2). Antibiotic-free chickens presented higher alpha-diversity, higher relative abundance of Deferribacteres, Fusobacteria, Bacteroidetes and Actinobacteria, and lower relative abundance of Firmicutes, Clostridiales and Enterobacteriales than antibiotic-fed chickens (P < 0.001) (Fig3). Microbial community composition significantly changed as birds aged. In experimental farm, microbial community composition was significant different for 7, 21 and 35 day old broilers (P < 0.001), and alpha diversity increased from 7 to 21d (P < 0.024), but not from 21 to 35d; whereas, in organic systems, increases in alpha-diversity were observed from 7d to 21d, and from 21d to 35d (P < 0.05). Broilers and layers raised together showed no differences in microbiota composition and alpha diversity (P > 0.8). It is concluded that production practices consistently impact microbial composition, and that antibiotics significantly reduces microbial diversity. We are now exploring the impact of differential colonization in a controlled setting, to determine the impact of the microbes associated with extensively raised chickens. This study will support future research and the development of methods to isolate and introduce beneficial microbes to commercial systems.

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Exploring microbial determinants of apple replant disease (ARD): a microhabitat approach under split-root design

FEMS Microbiology Ecology ◽

10.1093/femsec/fiaa211 ◽

2020 ◽

Vol 96 (12) ◽

Author(s):

Alicia Balbín-Suárez ◽

Maik Lucas ◽

Doris Vetterlein ◽

Søren J Sørensen ◽

Traud Winkelmann ◽

...

Keyword(s):

Microbial Community ◽

Community Composition ◽

Microbial Community Composition ◽

Rrna Gene ◽

Apple Rootstocks ◽

Apple Replant Disease ◽

Alpha And Beta Diversity ◽

Replant Disease ◽

Split Root ◽

And Control

ABSTRACT Apple replant disease (ARD) occurs worldwide in apple orchards and nurseries and leads to a severe growth and productivity decline. Despite research on the topic, its causality remains unclear. In a split-root experiment, we grew ARD-susceptible ‘M26’ apple rootstocks in different substrate combinations (+ARD: ARD soil; -ARD: gamma-irradiated ARD soil; and Control: soil with no apple history). We investigated the microbial community composition by 16S rRNA gene amplicon sequencing (bacteria and archaea) along the soil–root continuum (bulk soil, rhizosphere and rhizoplane). Significant differences in microbial community composition and structure were found between +ARD and -ARD or +ARD and Control along the soil–root continuum, even for plants exposed simultaneously to two different substrates (-ARD/+ARD and Control/+ARD). The substrates in the respective split-root compartment defined the assembly of root-associated microbial communities, being hardly influenced by the type of substrate in the respective neighbor compartment. Root-associated representatives from Actinobacteria were the most dynamic taxa in response to the treatments, suggesting a pivotal role in ARD. Altogether, we evidenced an altered state of the microbial community in the +ARD soil, displaying altered alpha- and beta-diversity, which in turn will also impact the normal development of apple rhizosphere and rhizoplane microbiota (dysbiosis), concurring with symptom appearance.

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Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits

10.21203/rs.3.rs-400629/v1 ◽

2021 ◽

Author(s):

Hirotsugu Shiroma ◽

Satoshi Shiba ◽

Pande Putu Erawijantari ◽

Hiroyuki Takamaru ◽

Masayoshi Yamada ◽

...

Keyword(s):

Colorectal Cancer ◽

Random Forest ◽

Gut Microbiota ◽

Learning Algorithm ◽

Fusobacterium Nucleatum ◽

Shotgun Metagenomics ◽

Flight Mass Spectrometry ◽

Parvimonas Micra ◽

Increased Risk ◽

One Year

Abstract Background: Postoperative colorectal cancer (CRC) patients are at increased risk of developing metachronous CRC. Despite accumulating evidence indicating that the gut microbiota and metabolites can promote CRC carcinogenesis, the influence of surgery for CRC on the gut microbiota and metabolites remains partially understood. We hypothesized that if surgery does not eliminate the bacteria and metabolites promoting CRC carcinogenesis, these bacteria and metabolites might be associated with the development of metachronous CRC. To test this hypothesis, we collected 170 fecal samples from 85 CRC patients in pre- and approximately one year postsurgery status, and performed shotgun metagenomics sequencing and capillary electrophoresis time-of-flight mass spectrometry-based metabolomics analyses and compared pre- and postsurgery status.Results: CRC-associated bacteria such as Parvimonas micra and Fusobacterium nucleatum were significantly (P < 0.005) decreased after surgery. On the other hand, cholate, carcinogenesis-associated deoxycholate, its biotransformed genes (bai operon) from cholate to deoxycholate, and the contributing bacterium (Clostridium scindens) were significantly (P < 0.005) increased. Additionally, these alterations were only observed in postleft surgery. Cholate and glycocholate were significantly (P < 0.005) increased in postright surgery. We also developed a method for potential CRC risk assessment based on the gut microbiota and metabolomic compositions using a random forest machine learning algorithm and then applied it to postoperative patients. The estimated CRC risk based on the random forest algorithm was partially restored postsurgery. Conclusions: Our results indicate that the high potential CRC risk in CRC postoperative patients is associated with metabolites derived from the gut microbiota, which targets interventions to reduce the CRC risk.

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Analysis of changes in microbiome compositions related to the prognosis of colorectal cancer patients based on tissue-derived 16S rRNA sequences

Journal of Translational Medicine ◽

10.1186/s12967-021-03154-0 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Sukjung Choi ◽

Jongsuk Chung ◽

Mi-La Cho ◽

Donghyun Park ◽

Sun Shim Choi

Keyword(s):

Colorectal Cancer ◽

16S Rrna ◽

Pathogenic Bacteria ◽

Fusobacterium Nucleatum ◽

Amplicon Sequencing ◽

Normal Tissues ◽

16S Rrna Amplicon Sequencing ◽

Tumor Tissues ◽

Colorectal Cancer Patients ◽

Host Genes

Abstract Background Comparing the microbiome compositions obtained under different physiological conditions has frequently been attempted in recent years to understand the functional influence of microbiomes in the occurrence of various human diseases. Methods In the present work, we analyzed 102 microbiome datasets containing tumor- and normal tissue-derived microbiomes obtained from a total of 51 Korean colorectal cancer (CRC) patients using 16S rRNA amplicon sequencing. Two types of comparisons were used: ‘normal versus (vs.) tumor’ comparison and ‘recurrent vs. nonrecurrent’ comparison, for which the prognosis of patients was retrospectively determined. Results As a result, we observed that in the ‘normal vs. tumor’ comparison, three phyla, Firmicutes, Actinobacteria, and Bacteroidetes, were more abundant in normal tissues, whereas some pathogenic bacteria, including Fusobacterium nucleatum and Bacteroides fragilis, were more abundant in tumor tissues. We also found that bacteria with metabolic pathways related to the production of bacterial motility proteins or bile acid secretion were more enriched in tumor tissues. In addition, the amount of these two pathogenic bacteria was positively correlated with the expression levels of host genes involved in the cell cycle and cell proliferation, confirming the association of microbiomes with tumorigenic pathway genes in the host. Surprisingly, in the ‘recurrent vs. nonrecurrent’ comparison, we observed that these two pathogenic bacteria were more abundant in the patients without recurrence than in the patients with recurrence. The same conclusion was drawn in the analysis of both normal and tumor-derived microbiomes. Conclusions Taken together, it seems that understanding the composition of tissue microbiomes is useful for predicting the prognosis of CRC patients.

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Evaluation of the gut microbiome in association with biological signatures of inflammation in murine polytrauma and shock

Scientific Reports ◽

10.1038/s41598-021-85897-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sandra A. Appiah ◽

Christine L. Foxx ◽

Dominik Langgartner ◽

Annette Palmer ◽

Cristian A. Zambrano ◽

...

Keyword(s):

Gut Microbiota ◽

Community Composition ◽

Gut Microbiome ◽

Beta Diversity ◽

Microbial Community Composition ◽

Alpha Diversity ◽

Global Changes ◽

Rrna Gene ◽

Alpha And Beta Diversity ◽

Increased Risk

AbstractSevere injuries are frequently accompanied by hemorrhagic shock and harbor an increased risk for complications. Local or systemic inflammation after trauma/hemorrhage may lead to a leaky intestinal epithelial barrier and subsequent translocation of gut microbiota, potentially worsening outcomes. To evaluate the extent with which trauma affects the gut microbiota composition, we performed a post hoc analysis of a murine model of polytrauma and hemorrhage. Four hours after injury, organs and plasma samples were collected, and the diversity and composition of the cecal microbiome were evaluated using 16S rRNA gene sequencing. Although cecal microbial alpha diversity and microbial community composition were not found to be different between experimental groups, norepinephrine support in shock animals resulted in increased alpha diversity, as indicated by higher numbers of distinct microbial features. We observed that the concentrations of proinflammatory mediators in plasma and intestinal tissue were associated with measures of microbial alpha and beta diversity and the presence of specific microbial drivers of inflammation, suggesting that the composition of the gut microbiome at the time of trauma, or shortly after trauma exposure, may play an important role in determining physiological outcomes. In conclusion, we found associations between measures of gut microbial alpha and beta diversity and the severity of systemic and local gut inflammation. Furthermore, our data suggest that four hours following injury is too early for development of global changes in the alpha diversity or community composition of the intestinal microbiome. Future investigations with increased temporal-spatial resolution are needed in order to fully elucidate the effects of trauma and shock on the gut microbiome, biological signatures of inflammation, and proximal and distal outcomes.

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Elevational changes in bacterial microbiota structure and diversity in an arthropod-disease vector

10.1101/2021.06.02.446707 ◽

2021 ◽

Author(s):

Tuomas Aivelo ◽

Mélissa Lemoine ◽

Barbara Tschirren

Keyword(s):

Microbial Community ◽

Microbial Diversity ◽

Community Composition ◽

Vector Competence ◽

Microbial Community Composition ◽

Alpha Diversity ◽

Swiss Alps ◽

Elevational Gradients ◽

Disease Vector ◽

Bacterial Microbiota

Environmental conditions change rapidly along elevational gradients and have been found to affect community composition in macroscopic taxa, with lower diversity typically observed at higher elevations. In contrast, microbial community responses to elevation are still poorly understood. Specifically, the effects of elevation on vector-associated microbiota have not been studied to date, even though the within-vector microbial community is known to influence vector competence for a range of zoonotic pathogens. Here we characterize the structure and diversity of the bacterial microbiota in an important zoonotic disease vector, the sheep tick Ixodes ricinus, along replicated elevational gradient (630 - 1673 masl) in the Swiss Alps. 16S rRNA sequencing of the whole within-tick bacterial microbiota of questing nymphs and adults revealed a decrease in Faith's phylogenetic microbial alpha diversity with increasing elevation, while beta diversity analyses revealed a lower variation in microbial community composition at higher elevations. We also found a higher microbial diversity later in the season and significant differences in microbial diversity among tick life stages and sexes, with lowest microbial alpha diversity observed in adult females. No associations between tick genetic diversity and bacterial diversity were observed. Our study demonstrates systematic changes in tick bacterial microbiota diversity along elevational gradients. The observed patterns mirror diversity changes along elevational gradients typically observed in macroscopic taxa, and they highlight the key role of environmental factors in shaping within-host microbial communities in ectotherms.

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Interaction Between Host MicroRNAs and the Gut Microbiota in Colorectal Cancer

10.1101/192401 ◽

2017 ◽

Author(s):

Ce Yuan ◽

Michael Burns ◽

Subbaya Subramanian ◽

Ran Blekhman

Keyword(s):

Colorectal Cancer ◽

Gut Microbiome ◽

Normal Tissue ◽

Microbial Community Composition ◽

Taxonomic Composition ◽

Integrated Analysis ◽

Tissue Samples ◽

Microbiome Composition ◽

Normal Tissues ◽

Mirnas Expression

AbstractBackgroundAlthough variation in gut microbiome composition has been linked with colorectal cancer (CRC), the factors that mediate the interactions between CRC tumors and the microbiome are poorly understood. MicroRNAs (miRNAs) are known to regulate CRC progression and patient survival outcomes. In addition, recent studies suggested that host miRNAs can also regulate bacterial growth and influence the composition of the gut microbiome. Here, we investigated the association between miRNAs expression in human CRC tumor and normal tissues and the microbiome composition associated with these same tissues.MethodWe sequenced the small RNAs from patient-matched tumor and normal tissue samples collected from 44 human CRC patients performed an integrated analysis with microbiome taxonomic composition data from these same samples. We then interrogated the functions of the bacteria correlated with miRNAs that were differentially expressed (DE) between tumor and matched normal tissues, as well as the functions of miRNAs correlated with bacterial taxa that have been previously associated with CRC, including Fusobacterium, Providencia, Bacteroides, Akkermansia, Roseburia, Porphyromonas, and Peptostreptococcus.ResultsWe identified 76 miRNAs as DE between CRC and normal tissue, including known oncogenic miRNAs miR-182, miR-503, and miR-17∼92. These DE miRNAs were correlated with the relative abundance of several bacterial taxa, including Firmicutes, Bacteroidetes, and Proteobacteria. Bacteria correlated with DE miRNAs were enriched with distinct predicted metabolic categories. Additionally, we found that miRNAs correlated with CRC-associated bacteria are predicted to regulate targets that are relevant for host-microbiome interactions, and highlight a possible role for miRNA-driven glycan production in the recruitment of pathogenic microbial taxa.ConclusionsOur work characterized a global relationship between microbial community composition and miRNA expression in human CRC tissues. Our results support a role for miRNAs in mediating a bi-directional host-microbiome interaction in CRC. In addition, we highlight sets of potentially interacting microbes and host miRNAs, suggesting several pathways that can be targeted via future therapies.

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Evaluating the Impact of Wastewater Effluent on Microbial Communities in the Panke, an Urban River

Water ◽

10.3390/w11050888 ◽

2019 ◽

Vol 11 (5) ◽

pp. 888 ◽

Cited By ~ 2

Author(s):

Marcella Nega ◽

Burga Braun ◽

Sven Künzel ◽

Ulrich Szewzyk

Keyword(s):

Microbial Community ◽

16S Rrna ◽

16S Rrna Gene ◽

Sampling Site ◽

River Sediments ◽

Microbial Community Composition ◽

Rrna Gene ◽

Sequencing Data ◽

Alpha And Beta Diversity ◽

The Impact

Pharmaceuticals are consumed in high amounts and can enter as emerging organic compounds in surface waters as they are only partially retained in wastewater treatment plants (WWTPs). Receiving pharmaceuticals may burden the aquatic environment, as they are designed to be bioactive even at low concentrations. Sediment biofilm populations were analyzed in river sediments due to the exposure of an inflow of WWTP effluents. Illumina MiSeq 16S rRNA gene amplicon sequencing was performed of 108 sediment samples, which were taken from multiple cores within three sampling locations in the Panke River, with one sampling site located downstream of the inflow. Sequencing data were processed to infer microbial community structure in samples concerning the environmental variables, such as micropollutants and physicochemical parameters measured for each core. More than 25 different micropollutants were measured in pore water samples, in which bezafibrate, clofibric acid, carbamazepine, and diclofenac were detected at high concentrations. Bacterial 16S rRNA gene amplicons revealed Nitrospirae, Proteobacteria, Chloroflexi, Actinobacteria, Acidobacteria, Bacteroidetes, and Ignavibacteriae as the most abundant groups in the samples. Differences in microbial community composition were observed with respect to micropollutants. However, our findings revealed that the composition of the microbial community was not only governed by the effluent. The significant changes in the alpha- and beta-diversity were explained by phenobarbital and SO42−, which did not originate from the WWTP indicating that more unobserved factors are also likely to play a role in affecting the biofilm community’s composition.

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