Association of the anorectal microbiome and patient-reported gastrointestinal outcomes in patients with anal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15504-e15504
Author(s):  
Ramez Kouzy ◽  
Daniel Lin ◽  
Molly Blue El Alam ◽  
Joseph Abi Jaoude ◽  
Grace L. Smith ◽  
...  

e15504 Background: Among patients with anal cancer undergoing chemoradiotherapy, the association between the microbiome and toxicity is not well documented. We sought to quantify the gastrointestinal-related patient-reported outcomes (PROs) and local microbiome profiles of patients with anal cancer receiving chemoradiotherapy in order to check for potential profiles that can help in predicting toxicity during treatment. Methods: We prospectively followed patients with non-metastatic squamous cell carcinoma of the anal canal who received definitive chemoradiotherapy. Anorectal swab samples were collected before treatment initiation and at 4 subsequent timepoints. Consequently, PROs were collected using the bowel subdomain of the Expanded Prostate Cancer Index Composite (EPIC). Samples were sequenced using 16S rRNA of the V4 region. Sequence reads were grouped by amplicon sequence variants (ASV’s) representative of unique bacterial species. We then used Linear discriminant analysis Effect Size (LEfSe) with an effect size of 4 to identify taxa at baseline that were differentially enriched in patients with high vs. low toxicity by end of treatment. We compared the EPIC scores with the relative abundance of species identified in the LEfSe using a paired Wilcoxon test. Results: The study included 22 patients (18 women and 4 men), whose median age was 59 years. Most patients were Stage III (59%) with negative HIV status (94%). The majority of patients (91%) received standard of care chemoradiotherapy. Overall toxicity was the highest at week 5 of treatment. At all individual time points, alpha diversity of the microbiome did not correlate with patient-reported GI function, additionally overall baseline diversity was not predictive of eventual GI outcomes. The LEfSe identified that patients with low patient reported toxicity at week 5 had higher of abundance of Selenomonas at baseline, while patients with higher toxicity had high abundance of baseline Actinobacteria, Peptoniphilus, Clostridiales , and Clostridia. When comparing the relative abundance of bacterial species among patients with high and low toxicities, patients with higher relative abundance of Clostridia and Actinobacteria had significantly higher toxicity (p = 0.03). Conclusions: Certain microbiome profiles at baseline are associated with anal cancer patients’ gastrointestinal-related PROs during chemoradiation. Our data provide novel avenues to study the potential uses of the local microbiome as a biomarker in predicting treatment toxicities in anal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 4-4
Author(s):  
Ramez Kouzy ◽  
Daniel Lin ◽  
Sonal Suresh Noticewala ◽  
Lauren Elizabeth Colbert ◽  
Cullen M. Taniguchi

4 Background: Anal cancer is a rare, but treatable, malignancy caused by the human papilloma virus (HPV). Because anal cancer is uncommon and carries a significant social stigma, this disease has rarely been studied in a prospective fashion, creating a large knowledge gap of which biological factors can improve treatment responses, particularly the microbiome which regulates many facets of oncobiology. Methods: We collected microbiome samples before, during, and after definitive chemoradiation for localized anal cancer as part of an IRB-approved institutional clinical trial (2017-0606). Samples were collected by a non-invasive swab biopsy that enabled collection of tumor cells and microbiome during standard-of-care treatment visits. Bacterial genomic DNA is extracted using MO BIO PowerSoil DNA Isolation Kit (MO BIO Laboratories) and the 16S rDNA V4 region is amplified by PCR and sequenced on the MiSeq platform (Illumina) using the 2x250 bp paired-end protocol, yielding pair-end reads that overlapped almost completely. Sequence read pairs are demultiplexed using unique molecular barcodes, and reads are merged using USEARCH version 7.0.1090 and grouped by organizational taxonomy units (OTU’s) representative of unique bacterial species. Responders are were those patients who had more than 60% tumor shrinkage by MRI at the midpoint of treatment, and all others were considered non-responders. Results: As of June 2019 we enrolled 17 patients and analyzed 14. The majority of patients (10/14, 71.4%) were responders but unfortunately, 4 patients developed in-field recurrences of their anal cancer within a year after their treatment ended and were all T3 or T4 tumors. We found that alpha-diversity of the microbiome did not change during chemoradiation, but non-responders exhibited a lower alpha diversity compared to responders at baseline. Furthermore, specific taxa were correlated with treatment response, which imply a basis for future therapy. Conclusions: The alpha diversity of the microbiome is correlated with treatment response in HPV+ anal cancer. The idenitification of specific bacterial species between responders and non-responder might pave the way for more effective therapeis in the future.


2021 ◽  
Author(s):  
Daniel Lin ◽  
Molly B El Alam ◽  
Joseph Abi Jaoude ◽  
Ramez Kouzy ◽  
Jae L Phan ◽  
...  

IMPORTANCE: Patients with localized squamous cell carcinoma of the anus (SCCA) who experience treatment toxicity or recurrences have few therapeutic options. Investigation into the microbiome's influence on treatment toxicity or its potential use as a predictive biomarker in this rare disease could improve these patients' outcomes. OBJECTIVE: To longitudinally characterize the SCCA tumor microbiome and assess its association with treatment-related toxicities. DESIGN: Prospective cohort study. SETTING: Single tertiary cancer center. PARTICIPANTS: Twenty-two patients with biopsy-confirmed non-metastatic SCCA receiving standard-of-care chemoradiotherapy as part of an Institutional Review Board-approved study from April 2017 to July 2019. MAIN OUTCOMES AND MEASURES: Diversity and taxonomic characterization of the SCCA microbiome throughout chemoradiotherapy using swab-based anorectal microbial specimen collection and 16S rRNA gene sequencing. RESULTS: Twenty-two SCCA patients were included in this study with a median (range) age of 58.5 (39-77), and 18 (82%) were women. Alpha diversity remained relatively stable throughout chemoradiotherapy, except for decreases in the Chao1 (P=0.03) and Observed Features (P=0.03) indices at week 5 relative to baseline. Tumor microbial compositions measured using weighted UniFrac changed significantly by the end of treatment (P=0.03). Linear discriminant analysis effect sizes revealed differential enrichment of bacteria at specific time points, including the enrichment of Clostridia at both baseline and follow-up and the enrichment of Corynebacterium at week 5. Patients experiencing high toxicity at week 5 had higher relative abundances of Clostridia, Actinobacteria, and Clostridiales at baseline (P=0.03 for all). CONCLUSIONS AND RELEVANCE: Our study presents the first longitudinal characterization of the SCCA microbiome throughout chemoradiation. The tumor microbiome undergoes significant changes during and after chemoradiotherapy, and patient-reported toxicity levels are associated with patients' microbial profiles. Further studies into these microbial characterizations and associations are needed to elucidate the tumor microbiome's role in predicting treatment-related outcomes for SCCA patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yuchuan Li ◽  
Qiuxia Liu ◽  
Chunting Peng ◽  
Bing Ruan

Although the role of the gut microbiota in obesity has recently received considerable attention, the exact mechanism is unclear. This study was aimed at investigating the profiles of bacterial communities in fecal samples and differentially expressed proteins (DEPs) in the peripheral blood in mice fed a high-fat diet (HFD) and standard diet (SD) and at providing new insights into the pathogenesis of obesity. The profiles of bacterial communities in fecal samples and DEPs in the peripheral blood were characterized in mice fed HFD and SD, respectively. The levels of 3 DEPs increased in HFD mice. The alpha diversity was significantly lower after 4 and 12 weeks in HFD mice. The beta diversity was higher after 4, 8, and 12 weeks in HFD mice. A total of 16 gut bacterial clades were significantly different with the linear discriminant analysis (LDA) score higher than 4 over time. The relative abundance levels of Proteobacteria and Deferribacteres were higher, while those of Bacteroidetes and Firmicutes were lower in HFD mice at the phylum level. The relative abundance of Desulfovibrionaceae and Rikenellaceae increased in HFD mice at the family level. The relative abundance of the Bacteroidetes_S24-7_group and Lachnospiraceae was lower in HFD mice. The gut microbiota had a significant correlation with serum lipid indexes and expression of DEPs at the phylum and family levels. The changes in the gut microbiota of HFD mice and their associations with the levels of inflammatory proteins could be one of the major etiological mechanisms underlying obesity.


2020 ◽  
Vol 9 (12) ◽  
pp. 4068
Author(s):  
Jean-Luc C. Mougeot ◽  
Micaela F. Beckman ◽  
Holden C. Langdon ◽  
Michael T. Brennan ◽  
Farah Bahrani Mougeot

The endogenous microbiome of healthy individuals in oral cavities is diverse, representing over 700 bacterial species. Imbalance in oral and gut microbiome composition and associated gene expression has been linked to different forms of hematological (blood) cancers. Our objective is to compare oral microbiome profiles of patients with blood cancers (BC group: N = 39 patients, n = 124 oral samples) to those of healthy control subjects (HC group: N = 27 subjects, n = 100 oral samples). Saliva samples and swabs of buccal mucosa, supragingival plaque, and tongue were collected from blood cancer patients and healthy controls. Next-generation sequencing (16S-rRNA gene V3–V4 region) was used to determine the relative abundance of bacterial taxa present at the genus and species levels. Differences in oral microbiome beta-diversity were determined using multivariate permutational analysis of variance (PERMANOVA). Linear discriminant analysis (LDA) effect size (LEfSe) analysis was performed to identify differentiating bacterial taxa in pairwise comparisons. The PATRICv3.6.7 online tool was used to determine the predominance of potential pathogenicity in the BC group. The oral microbiome beta-diversities of the BC and HC groups differed and corresponded to a reduced alpha-diversity in the BC group. LEfSe analysis showed significant LDA scores for Actinomyces and Rothia spp., differentiating the BC group from the HC group. In silico analysis using PATRICv3.6.7 demonstrated that the groups of bacteria possessing traits of “antibiotic resistance”, “oral pathogen”, and “virulence” was enriched in the BC group. Although 56% of the BC patients received antibiotics within two weeks of the oral bacterial sampling, Actinomyces genus remained the top differentiating feature in the BC group regardless of the administration of antibiotics, while Rothia dentocariosa was detected as the top differentiating feature in the BC patients who did not receive antibiotics, but not in those who received antibiotics. Further investigation is needed to better understand the interactions of certain oral species with the host immune system to better characterize clinically relevant associations with hematological cancers.


2020 ◽  
Vol 16 (12) ◽  
pp. e1524-e1531 ◽  
Author(s):  
Ramez Kouzy ◽  
Joseph Abi Jaoude ◽  
Daniel Lin ◽  
Molly B. El Alam ◽  
Bruce D. Minsky ◽  
...  

PURPOSE: Among patients with anal cancer, chemoradiotherapy is often associated with toxicities that diminish quality of life. We describe the GI-related patient-reported outcomes (PROs) of patients with anal cancer receiving chemoradiotherapy to improve patient-physician communication. METHODS: We prospectively followed patients with nonmetastatic squamous cell carcinoma of the anal canal who received definitive chemoradiotherapy. Patients completed the bowel subdomain of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire before treatment and at 4 subsequent timepoints. We used the paired Wilcoxon test to compare EPIC scores at different times. RESULTS: The study included 21 patients; median age was 57 years. Most patients (52%) had T2 and either N0 or N1 disease (81%). Most patients (91%) received chemotherapy with cisplatin-fluorouracil and either intensity-modulated radiotherapy or volumetric modulated arc therapy. Compared with the patients’ median overall summary score at baseline (66), their median score at 1 week (82) was higher ( P = .009), whereas their median score at 5 weeks (54) was lower ( P = .025). The patients’ median overall summary score at baseline and at 3 months did not differ ( P = .919). Three months after radiotherapy, most patients reported minimal adverse effects compared with baseline. CONCLUSION: The GI-related PROs of patients with anal cancer tend to fluctuate during radiotherapy but return to baseline by 3 months, at which time most patients report few or no residual adverse effects. We provide a clear timeline of GI acute toxicity using sequential PRO measurements that will improve patient-physician communication regarding expectations for cancer treatment.


2020 ◽  
Vol 30 (8) ◽  
pp. 1151-1156
Author(s):  
Travis T Sims ◽  
Greyson W G Biegert ◽  
Doreen Ramogola-Masire ◽  
Kebatshabile Ngoni ◽  
Travis Solley ◽  
...  

IntroductionWe characterized the cervical 16S rDNA microbiome of patients in Botswana with high-grade cervical dysplasia and locally advanced cervical cancer.MethodsThis prospective study included 31 patients: 21 with dysplasia and 10 with cancer. The Shannon diversity index was used to evaluate alpha (intra-sample) diversity, while the UniFrac (weighted and unweighted) and Bray–Curtis distances were employed to evaluate beta (inter-sample) diversity. The relative abundance of microbial taxa was compared among samples using linear discriminant analysis effect size.ResultsAlpha diversity was significantly higher in patients with cervical cancer than in patients with cervical dysplasia (P<0.05). Beta diversity also differed significantly (weighted UniFrac Bray–Curtis, P<0.01). Neither alpha diversity (P=0.8) nor beta diversity (P=0.19) varied by HIV status. The results of linear discriminant analysis effect size demonstrated that multiple taxa differed significantly between patients with cervical dysplasia vs cancer. Lachnospira bacteria (in the Clostridia class) were particularly enriched among cervical dysplasia patients, while Proteobacteria (members of the Firmicutes phyla and the Comamonadaceae family) were enriched in patients with cervical cancer.DiscussionThe results of our study suggest that differences exist in the diversity and composition of the cervical microbiota between patients with cervical dysplasia and patients with cervical cancer in Botswana. Additional studies are warranted to validate these findings and elucidate their clinical significance among women living in sub-Saharan Africa, as well as other regions of the world.


2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0002
Author(s):  
Judith Baumhauer ◽  
Jack Teitel ◽  
Allison McIntyre ◽  
David Mitten ◽  
Jeff Houck

Category: Other Introduction/Purpose: Each year approximately 30-40% of people over the age of 65 fall. Approximately one half of these falls result in an injury with the estimated annual direct medical costs of $30 billion. Pain, mobility issues, neuropathy and post-operative weight bearing limitations make foot and ankle patients particularly vulnerable to falls. Current approaches to determine at risk patients are cumbersome and time consuming requiring performance testing and “hands on” clinical assessment. The efficiency of obtaining PRO, such as PROMIS, in the clinical arena has been well documented. The purpose of this study is determine if patient reported outcomes (PROMIS) can identify orthopaedic and specifically foot and ankle patients at risk to fall. Methods: Prospective patient reported outcomes (PROMIS CAT physical function, pain interference and depression and CMS fall risk assessment questions) and patient demographics were collected for all patients at each clinic visit from an academic orthopaedic multi-specialty practice between January 2015 and November 2017. Standardized yes/no validated self-reported fall risk questions include: “Have you fallen in the last year?” and “Do you feel you are at risk of falling?” Histograms, t-tests, confidence intervals and effect size were used to determine the fall risk “YES” patients were different than the “NO” for ALL orthopaedic patients and specifically foot and ankle patients. Logistic Regression was used to determine if age, gender, height, weight, and PROMIS scales predicted self-reported falls risk. Results: 94,761 orthopaedic patients comprising 315,273 visits (44% male, mean age 53.7+/-17 years) and 13,720 foot/ankle patients comprising 33,480 visits (37% male, mean age 52.7+/-16.1 years) had complete data for analysis. Table 1 provides the means/SD/p-values/effect sizes for patient self-identifying at risk to fall stratified by PROMIS PF/ PI/Dep t-scores. Although all PROMIS scores demonstrated significant impairment between patients at risk designation (yes/no), PROMIS PF had the largest effect size for ALL Ortho and FOOT AND ANKLE patients (0.8 and 0.7 respectively). Patients who are at risk to fall have PROMIS PF t-scores >1.5 lower than the United States normative population while the patients not at risk are less <1 SD. In the adjusted regression models gender and PROMIS PF had the largest coefficients. Conclusion: Falls are a major threat to quality of life and independence yet prevention/treatment strategies are difficult to implement across a health system. There is also a tremendous societal cost with orthopaedic surgeons often the recipient of these debilitated patients. PROMIS assessments are part of the AOFAS OFAR initiative to track patient recovery with treatment and can additional be used to fulfill a quality indicator requirement by CMS. This study demonstrates these assessments (PROMIS threshold values) can also be linked to self-report falls risk (yes/no) and may identify patients at risk with no face to face time required from the provider.


2021 ◽  
Vol 9 (3) ◽  
pp. 617
Author(s):  
Zhenbing Wu ◽  
Qianqian Zhang ◽  
Yaoyao Lin ◽  
Jingwen Hao ◽  
Shuyi Wang ◽  
...  

The gill and gastrointestinal tract are primary entry routes for pathogens. The symbiotic microbiota are essential to the health, nutrition and disease of fish. Though the intestinal microbiota of Nile tilapia (Oreochromis niloticus) has been extensively studied, information on the mucosa-associated microbiota of this species, especially the gill and gastrointestinal mucosa-associated microbiota, is lacking. This study aimed to characterize the gill and gastrointestinal mucosa- and digesta-associated microbiota, as well as the intestinal metabolite profiles in the New Genetically Improved Farmed Tilapia (NEW GIFT) strain of farmed adult Nile tilapia by high-throughput sequencing and gas chromatography/mass spectrometry metabolomics. The diversity, structure, composition, and predicted function of gastrointestinal microbiota were significantly different across gastrointestinal regions and sample types (Welch t-test; p < 0.05). By comparing the mucosa- and digesta-associated microbiota, linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed that Pelomonas, Ralstoniapickettii, Comamonadaceae, and Staphylococcus were significantly enriched in the mucosa-associated microbiota, whereas many bacterial taxa were significantly enriched in the digesta-associated microbiota, including Chitinophagaceae, Cetobacterium, CandidatusCompetibacter, Methyloparacoccus, and chloroplast (LDA score > 3.5). Furthermore, Undibacterium, Escherichia–Shigella, Paeniclostridium, and Cetobacterium were dominant in the intestinal contents and mucosae, whereas Sphingomonasaquatilis and Roseomonasgilardii were commonly found in the gill and stomach mucosae. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) analysis revealed that the predictive function of digesta-associated microbiota significantly differed from that of mucosa-associated microbiota (R = 0.8152, p = 0.0001). In addition, our results showed a significant interdependence between specific intestinal microbes and metabolites. Notably, the relative abundance values of several potentially beneficial microbes, including Undibacterium, Crenothrix, and Cetobacterium, were positively correlated with most intestinal metabolites, whereas the relative abundance values of some potential opportunistic pathogens, including Acinetobacter, Mycobacterium, Escherichia–Shigella, Paeniclostridium, Aeromonas, and Clostridiumsensustricto 1, were negatively correlated with most intestinal metabolites. This study revealed the characteristics of gill and gastrointestinal mucosa-associated and digesta-associated microbiota of farmed Nile tilapia and identified a close correlation between intestinal microbes and metabolites. The results serve as a basis for the effective application of targeted probiotics or prebiotics in the diet to regulate the nutrition and health of farmed tilapia.


Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2139
Author(s):  
Feilong Deng ◽  
Yushan Li ◽  
Yunjuan Peng ◽  
Xiaoyuan Wei ◽  
Xiaofan Wang ◽  
...  

Archaea are an essential class of gut microorganisms in humans and animals. Despite the substantial progress in gut microbiome research in the last decade, most studies have focused on bacteria, and little is known about archaea in mammals. In this study, we investigated the composition, diversity, and functional potential of gut archaeal communities in pigs by re-analyzing a published metagenomic dataset including a total of 276 fecal samples from three countries: China (n = 76), Denmark (n = 100), and France (n = 100). For alpha diversity (Shannon Index) of the archaeal communities, Chinese pigs were less diverse than Danish and French pigs (p < 0.001). Consistently, Chinese pigs also possessed different archaeal community structures from the other two groups based on the Bray–Curtis distance matrix. Methanobrevibacter was the most dominant archaeal genus in Chinese pigs (44.94%) and French pigs (15.41%), while Candidatus methanomethylophilus was the most predominant in Danish pigs (15.71%). At the species level, the relative abundance of Candidatus methanomethylophilus alvus, Natrialbaceae archaeon XQ INN 246, and Methanobrevibacter gottschalkii were greatest in Danish, French, and Chinese pigs with a relative abundance of 14.32, 11.67, and 16.28%, respectively. In terms of metabolic potential, the top three pathways in the archaeal communities included the MetaCyc pathway related to the biosynthesis of L-valine, L-isoleucine, and isobutanol. Interestingly, the pathway related to hydrogen consumption (METHANOGENESIS-PWY) was only observed in archaeal reads, while the pathways participating in hydrogen production (FERMENTATION-PWY and PWY4LZ-257) were only detected in bacterial reads. Archaeal communities also possessed CAZyme gene families, with the top five being AA3, GH43, GT2, AA6, and CE9. In terms of antibiotic resistance genes (ARGs), the class of multidrug resistance was the most abundant ARG, accounting for 87.41% of archaeal ARG hits. Our study reveals the diverse composition and metabolic functions of archaea in pigs, suggesting that archaea might play important roles in swine nutrition and metabolism.


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