The Regional Specificity of Mucosa-Associated Microbiota in Patients with Distal Colorectal Cancer

Digestion ◽  
2021 ◽  
pp. 1-9
Author(s):  
Yoshihiko Kono ◽  
Ryo Inoue ◽  
Takumi Teratani ◽  
Mineyuki Tojo ◽  
Yuko Kumagai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fusobacterium Nucleatum ◽  
Amplicon Sequencing ◽  
Normal Mucosa ◽  
Rrna Gene ◽  
Normal Tissues ◽  
Streptococcus Anginosus ◽  
Significant Difference ◽  
Regional Specificity ◽  
Tissue Specimens

<b><i>Background/Aims:</i></b> Recent studies have demonstrated that the populations of several microbes are significantly increased in fecal samples from patients with colorectal cancer (CRC), suggesting their involvement in the development of CRC. The aim of this study was to identify microbes which are increased in distal CRCs and to identify the specific location of microbes increased in mucosal tissue around the tumor. <b><i>Methods:</i></b> Tissue specimens were collected from surgical resections of 28 distal CRCs. Five samples were collected from each specimen (location A: tumor, B: adjacent normal mucosa, C: normal mucosa 1 cm proximal to the tumor, D: normal mucosa 3 cm proximally, and E: normal mucosa 6 cm proximally). The microbiota in the sample were analyzed using 16S rRNA gene amplicon sequencing and the relative abundance (RA) of microbiota compared among the 5 locations. <b><i>Results:</i></b> At the genus level, the RA of <i>Fusobacterium</i> and <i>Streptococcus</i> at location A was the highest among the 5 locations, significantly different from that in location E. The dominant species of each genus was <i>Fusobacterium nucleatum</i> and <i>Streptococcus anginosus.</i> The RAs of these species gradually decreased from locations B to E with a statistically significant difference in <i>F. nucleatum</i>. The genus <i>Peptostreptococcus</i> also showed a similar trend, and the RA of <i>Peptostreptococcus stomatis</i> in location A was significantly associated with depth of tumor invasion and tumor size. <b><i>Conclusion:</i></b> Although the clinical relevance is not clear yet, these results suggest that <i>F. nucleatum, S. anginosus</i>, and <i>P. stomatis</i> can spread to the adjacent normal tissues and may change the surrounding microenvironment to support the progression of CRC.

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

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.

scholarly journals Association between colorectal cancer and Fusobacterium nucleatum and Bacteroides fragilis bacteria in Iranian patients: a preliminary study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Aref Shariati ◽  
Shabnam Razavi ◽  
Ehsanollah Ghaznavi-Rad ◽  
Behnaz Jahanbin ◽  
Abolfazl Akbari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Relative Abundance ◽  
Normal Tissue ◽  
Bacteroides Fragilis ◽  
Fusobacterium Nucleatum ◽  
Normal Mucosa ◽  
Clinicopathologic Characteristics ◽  
Tissue Samples ◽  
Adjacent Normal Mucosa ◽  
Iranian Patients

Abstract Background and aim Recent studies have proposed that commensal bacteria might be involved in the development and progression of gastrointestinal disorders such as colorectal cancer (CRC). Therefore, in this study, the relative abundance of Fusobacterium nucleatum, Bacteroides fragilis, Streptococcus bovis/gallolyticus, and Enteropathogenic Escherichia coli (EPEC) in CRC tissues, and their association with clinicopathologic characteristics of CRC was investigated in Iranian patients. Moreover, the role of these bacteria in the CRC-associated mutations including PIK3CA, KRAS, and BRAF was studied. Method To these ends, the noted bacteria were quantified in paired tumors and normal tissue specimens of 30 CRC patients, by TaqMan quantitative Real-Time Polymerase Chain Reaction (qPCR). Next, possible correlations between clinicopathologic factors and mutations in PIK3CA, KRAS, and BRAF genes were analyzed. Results In studied samples, B. fragilis was the most abundant bacteria that was detected in 66 and 60% of paired tumor and normal samples, respectively. Furthermore, 15% of the B. fragilis-positive patients were infected with Enterotoxigenic B. fragilis (ETBF) in both adenocarcinoma and matched adjacent normal samples. F. nucleatum was also identified in 23% of tumors and 13% of adjacent normal tissue samples. Moreover, the relative abundance of these bacteria determined by 2-ΔCT was significantly higher in CRC samples than in adjacent normal mucosa (p < 0.05). On the other hand, our findings indicated that S. gallolyticus and EPEC, compared to adjacent normal mucosa, were not prevalent in CRC tissues. Finally, our results revealed a correlation between F. nucleatum-positive patients and the KRAS mutation (p = 0.02), while analyses did not show any association between bacteria and mutation in PIK3CA and BRAF genes. Conclusion The present study is the first report on the analysis of different bacteria in CRC tissue samples of Iranian patients. Our findings revealed that F. nucleatum and B. fragilis might be linked to CRC. However, any link between gut microbiome dysbiosis and CRC remains unknown.

scholarly journals Supplementation of a lacto-fermented rapeseed-seaweed blend promotes gut microbial- and gut immune-modulation in weaner piglets

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Hui ◽  
Paulina Tamez-Hidalgo ◽  
Tomasz Cieplak ◽  
Gizaw Dabessa Satessa ◽  
Witold Kot ◽  
...  
Keyword(s):  
Immune Modulation ◽  
Amplicon Sequencing ◽  
Saccharina Latissima ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Colon Mucosa ◽  
Weaned Piglets ◽  
Brown Macroalgae ◽  
Blood Concentrations ◽  
Significant Difference

Abstract Background The direct use of medical zinc oxide in feed will be abandoned after 2022 in Europe, leaving an urgent need for substitutes to prevent post-weaning disorders. Results This study investigated the effect of using rapeseed-seaweed blend (rapeseed meal added two brown macroalgae species Ascophylum nodosum and Saccharina latissima) fermented by lactobacilli (FRS) as feed ingredients in piglet weaning. From d 28 of life to d 85, the piglets were fed one of three different feeding regimens (n = 230 each) with inclusion of 0%, 2.5% and 5% FRS. In this period, no significant difference of piglet performance was found among the three groups. From a subset of piglets (n = 10 from each treatment), blood samples for hematology, biochemistry and immunoglobulin analysis, colon digesta for microbiome analysis, and jejunum and colon tissues for histopathological analyses were collected. The piglets fed with 2.5% FRS manifested alleviated intraepithelial and stromal lymphocytes infiltration in the gut, enhanced colon mucosa barrier relative to the 0% FRS group. The colon microbiota composition was determined using V3 and V1-V8 region 16S rRNA gene amplicon sequencing by Illumina NextSeq and Oxford Nanopore MinION, respectively. The two amplicon sequencing strategies showed high consistency between the detected bacteria. Both sequencing strategies indicated that inclusion of FRS reshaped the colon microbiome of weaned piglets with increased Shannon diversity. Prevotella stercorea was verified by both methods to be more abundant in the piglets supplied with FRS feed, and its abundance was positively correlated with colonic mucosa thickness but negatively correlated with blood concentrations of leucocytes and IgG. Conclusions FRS supplementation relieved the gut lymphocyte infiltration of the weaned piglets, improved the colon mucosa barrier with altered microbiota composition. Increasing the dietary inclusion of FRS from 2.5% to 5% did not lead to further improvements.

The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer

Chemotherapy ◽  
2022 ◽  
pp. 1-10
Author(s):  
Cheng Yang ◽  
Na Xie ◽  
Zhifei Luo ◽  
Xiling Ruan ◽  
Yixin Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Poor Prognosis ◽  
Cancer Metastasis ◽  
Mrna Level ◽  
Normal Mucosa ◽  
Tnm Stage ◽  
Expression Levels ◽  
Normal Tissues

<b><i>Introduction:</i></b> We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). <b><i>Methods:</i></b> CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. <b><i>Results:</i></b> Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. <b><i>Conclusion:</i></b> CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.

scholarly journals POTENTIAL PREVENTIVE EFFECT OF LACTOBACILLUS ACIDOPHILUS AND LACTOBACILLUS PLANTARUM IN PATIENTS WITH POLYPS OR COLORECTAL CÂNCER

2018 ◽  
Vol 55 (4) ◽  
pp. 407-411 ◽  
Author(s):  
Nazi ZINATIZADEH ◽  
Farzad KHALILI ◽  
Parviz FALLAH ◽  
Malihe FARID ◽  
Maryam GERAVAND ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lactobacillus Plantarum ◽  
Lactobacillus Acidophilus ◽  
Rrna Gene ◽  
Preventive Effect ◽  
Healthy Group ◽  
Significant Difference ◽  
Average Copy ◽  
And Gender ◽  
Colorectal Cancer Patients

ABSTRACT BACKGROUND: Colorectal cancer is one of the major causes of death worldwide. Many studies have been done on the biology of its formation as well as its treatment in recent years. One of the factors involved in the formation or treatment of this malignancy can be attributed to the microbial flora in the intestine. OBJECTIVE: This study investigate the potential preventive effect of Lactobacillus acidophilus and Lactobacillus plantarum in patients with polyps or colorectal cancer (CRC). METHODS: A total of 77 samples were selected in the form of three groups including individuals suffering from CRC, polyps and healthy subjects. Genomic DNA of fecal specimens and standard strains were extracted and amplified employing primers targeting of the 16S rRNA gene for initial detection. Absolute Real Time PCR quantification was used to determine the copy of the bacterial expression per gram of feces. RESULTS: No significant difference were observed between age and gender in the mentioned groups (P=0.06). The average copy number of Lactobacillus acidophilus shows Significant difference between the healthy group and those with polyps (P<0.0001), the healthy group and those with colorectal cancer (P<0.0001), as well as those with polyps and the colorectal cancer patients (P<0.0001). CONCLUSION: These results may indicate that taking Lactobacillus acidophilus in people with a family history of CRC and people with polyps may be a way of preventing, treating or reducing the severity of CRC.

Nfy-c expression in colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15086-e15086
Author(s):  
A. E. Kottorou ◽  
A. G. Antonacopoulou ◽  
L. Skarlas ◽  
P. D. Grivas ◽  
C. D. Scopa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Recurrence ◽  
Clinicopathological Parameters ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Expression Levels ◽  
Nuclear Factor Y ◽  
Significant Difference ◽  
Tissue Specimens

e15086 Background: Nuclear factor Y- C (NFY-C) gene encodes one of the three subunits of nuclear factor Y, a highly conserved transcription factor which binds to the promoters of a variety of genes, which are implicated in cell cycle progression, drug metabolism and antigen presentation. The purpose of the current study was to investigate the role of NFY-C in colorectal cancer by evaluating its mRNA expression in both malignant and normal colonic tissue from patients with colorectal carcinomas with and without disease relapse. Methods: Publicly available expression microarray data were analyzed to reveal elevated levels of NFY-C in patients with colorectal carcinoma who relapsed compared to patients who remained disease free. The mRNA levels of NFY-C were evaluated by quantitative RT-PCR in 81 neoplastic colorectal tissue specimens and 23 normal tissue specimens from patients with colorectal cancer who had undergone curative resections at the University Hospital of Patras, Greece, between 1995 and 2005. The mRNA levels were analysed in relation to clinicopathological parameters. Results: No significant difference was found in the expression levels of NFY-C between normal and malignant tissues. The expression levels of NFY-C were not related to age, gender, grade, stage or primary site of the disease. However, a statistically significant difference (p=0.02) was observed in NFY-C levels between patients with and without disease recurrence. More specifically, patients with low NFY-C levels relapsed more often than patients who overexpressed NFY-C. Nevertheless, the expression was not related to time to disease progression. Finally, patients with higher NFY-C expression levels seem to have improved survival, compared to patients with low NFY-C expression levels although the difference was not statistically significant. Conclusions: Expression levels of NFY-C seem to be associated with disease recurrence. The role of NFY-C in colorectal cancer warrants further investigation. No significant financial relationships to disclose.

Identification of epigenetic silencing of GCNT2 expression by comprehensive real-time PCR screening in colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 506-506
Author(s):  
Kazunorii Nakamura ◽  
Horomichi Sawaki ◽  
Keishi Yamashita ◽  
Masahiko Watanabe ◽  
Hisashi Narimatsu
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Real Time ◽  
Cell Lines ◽  
Real Time Pcr ◽  
Critical Role ◽  
Normal Mucosa ◽  
Primary Cancer ◽  
Normal Tissues ◽  
Cancer Tissues

506 Background: Glycoprotein expression profile has been proved to be dramatically altered in human cancers, however specific glycogenes which are aberrant in expression in cancer cells has not been fully identified. Recent accumulated evidence supported notion that the reduced expression of tumor suppressor genes is explained by DNA promoter methylation in human cancer. Methods: We used Comprehensive Real time PCR system (CRPS) for glycogenes (189 genes) to identify genes aberrantly expressed in colorectal cancer tissues (CRC) as compared to the corresponding normal mucosa tissues. GCNT2 was of particular interest among the identified genes in CRC. Results: (1) GCNT2 harbors 3 isoforms which have different promoter regions. (2) All of the 3 isoforms of GCNT2 genes were remarkably decreased in CRC as compared to the corresponding normal mucosa, and each isoform expression was strongly associated with other 2 isoforms in primary cancer tissues by TaqMan real time PCR (R = 0.99-995, p < 0.0001). (3) Among the 5 CRC cell lines (DLD1, HCT116, CACO2, LOVO), those which were silenced in expression were reactivated by demethylating agents such as 5-aza-2’ deoxycytidine and trichostatin A. (4) Promoter region of the variant 2 of GCNT2 was consistent with its silenced expression in CRC cell lines by cloned sequence, so we examined DNA methylation status of the promoter of the GCNT2 variant 2 in 50 primary cancer tissues and the corresponding normal tissues. Quantitative MSP revealed that almost half of normal tissues have methylation as high as tumor tissues, while, in the primary CRC with less methylation in the corresponding normal tissues, DNA methylation was higher in primary CRC tissues than in the corresponding normal tissues. Finally, GCNT2 variant 2 stable transfection induced expression of other 2 isoform variants. Conclusions: We identified novel methylation gene GCNT2 among the glycoenes. Glycoenes that were altered in genomic or epigenetic manner have been few, so GCNT2 may play a critical role in cancer progression through glycan change.

scholarly journals The Very Low Frequency of Epstein-Barr JC and BK Viruses DNA in Colorectal Cancer Tissues in Shiraz, Southwest Iran

2018 ◽  
Vol 67 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Jamal Sarvari ◽  
Shahab Mahmoudvand ◽  
Neda Pirbonyeh ◽  
Akbar Safaei ◽  
Seyed Younes Hosseini
Keyword(s):  
Colorectal Cancer ◽  
Dna Sequences ◽  
Low Frequency ◽  
Normal Tissues ◽  
Barr Virus ◽  
Total Dna ◽  
Epstein Barr ◽  
Tissue Specimens ◽  
Cancer Tissues ◽  
Southwest Iran

Viruses including Epstein-Barr virus (EBV), JCV and BKV have been reported to be associated with some cancers. The association of these viruses with colorectal cancers remains controversial. Our objective was to investigate their infections association with adenocarcinoma and adenomatous polyps of the colon. Totally, 210 paraffin-embedded tissue specimens encompassing 70 colorectal adenocarcinoma, 70 colorectal adenomatous and 70 colorectal normal tissues were included. The total DNA was extracted, then qualified samples introduced to polymerase chain reaction (PCR). The EBV, JCV and BKV genome sequences were detected using specific primers by 3 different in-house PCR assays. Out of 210 subjects, 98 cases were female and the rest were male. The mean age of the participants was 52 ± 1.64 years. EBV and JCV DNA was detected just in one (1.42%) out of seventy adenocarcinoma colorectal tissues. All adenomatous polyp and normal colorectal tissues were negative for EBV and JCV DNA sequences. Moreover, all the patients and healthy subjects were negative for BKV DNA sequences. The results suggested that EBV and JCV genomes were not detectable in the colorectal tissue of patients with colorectal cancer in our population. Hence, BKV might not be necessitated for the development of colorectal cancer. The findings merit more investigations.

scholarly journals Tumour Microbiome-Based Subtypes of Colorectal Cancer Correlate with Clinical Variables

2020 ◽  
Author(s):  
Barbora Zwinsová ◽  
Vyacheslav Petrov ◽  
Martina Hrivňáková ◽  
Stanislav Smatana ◽  
Lenka Micenková ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiome ◽  
Primary Tumour ◽  
Distant Metastases ◽  
Normal Mucosa ◽  
Tnm Staging ◽  
Response To Treatment ◽  
Clinical Variable ◽  
Rrna Gene ◽  
Clinical Variables

Abstract BackgroundLong-term dysbiosis of the gut microbiome has a significant impact on the development, progression and the aggressiveness of colorectal cancer (CRC) and may explain part of the observed heterogeneity of the disease from phenotypic, prognostic and response to treatment perspectives. Although the shifts in gut microbiome in the normal-adenoma-carcinoma sequence have been described, the landscape of microbiome within CRC and its associations with clinical variables remain under-explored. ResultsWe performed 16S rRNA gene sequencing of paired tumour tissue, adjacent visually-normal mucosa and stool swabs of N=186 patients with stage 0-IV CRC to describe the tumour microbiome and its association with clinical variable and to derive tumour microbial subtypes.We identified new genera never previously associated with CRC tumour mucosa (Flavonifractor, Haemophilus, Howardella, Pseudomonas, Sutterella, Treponema 2) or CRC (Actinobacillus, Aggregatibacter, Bergeyella, Phocaeiola, Defluviitaleaceae UCG-011, Massilia, Tyzzerella 4). The bacteria residing on tumour-mucosa were dominated by genera belonging to (potential) oral pathogens. Based on tumour microbial profiles, we stratified CRC patients into three subtypes. The subtypes were significantly associated with prognostic factors such as tumor grade, primary tumour sidedness and TNM staging, with one subtype enriched in tumours with poor prognosis. Further, we inspected the associations of microbiome with clinical variables in a subtype-agnostic setting. The primary tumour-associated clinical variables predominantly correlated with tumour mucosal microbiome, while the presence of local and distant metastases was mostly associated with the stool microbiome.ConclusionsUnderstanding the interactions of the bacteria residing on tumour mucosa within different CRC tumour microbiome subtypes will help to better understand the underlying biological background of the heterogeneity of this disease. Indeed, the tumour microbiome is a possible source of additional integrative markers of CRC patients’ survival and prognosis. We found that CRC microbiome is strongly correlated with clinical variables, but these associations are dependent on the microbial environment (tumour mucosa, normal mucosa, stool). Our study thus identifies limitations of the usage of microbiome composition as marker of CRC progression, suggesting the need of combining several sampling sites (e.g. stool and tumour swabs).

scholarly journals Trikafta therapy alters the CF lung mucus metabolome reshaping microbiome niche space

2021 ◽  
Author(s):  
Lauren Sosinski ◽  
Christian Martin-Hernandez ◽  
Kerri A Neugebauer ◽  
Lydia-Ann J Ghuneim ◽  
Douglas V Guzior ◽  
...  
Keyword(s):  
Drug Effects ◽  
Amplicon Sequencing ◽  
Kynurenine Pathway ◽  
Rrna Gene ◽  
Structural Modifications ◽  
Lung Microbiome ◽  
Fda Approval ◽  
Significant Difference ◽  
Before And After ◽  
Log Ratio

Novel small molecule therapies for cystic fibrosis (CF) are showing promising efficacy and becoming more widely available since recent FDA approval. The newest of these is a triple therapy of Elexacaftor-Tezacaftor-Ivacaftor (ETI). Little is known about how these drugs will affect polymicrobial lung infections, which are the leading cause of morbidity and mortality among people with CF (pwCF). We analyzed the sputum microbiome and metabolome from pwCF (n=24) before and after TKT therapy using 16S rRNA gene amplicon sequencing and untargeted metabolomics. The lung microbiome diversity, particularly its evenness, was increased (p = 0.044) and the microbiome profiles were different between individuals before and after therapy (PERMANOVA F=1.92, p=0.044). Despite these changes, the microbiomes were more similar within an individual than across the sampled population. There were no specific microbial taxa that were different in abundance before and after therapy, but collectively, the log-ratio of anaerobes to pathogens significantly decreased. The sputum metabolome also showed changes due to TKT. Beta-diversity increased after therapy (PERMANOVA F=4.22, p=0.022) and was characterized by greater variation across subjects while on treatment. This significant difference in the metabolome was driven by a decrease in peptides, amino acids, and metabolites from the kynurenine pathway. Metabolism of the three small molecules that make up TKT was extensive, including previously uncharacterized structural modifications. This study shows that TKT therapy affects both the microbiome and metabolome of airway mucus. This effect was stronger on sputum biochemistry, which may reflect changing niche spaces for microbial residency in lung mucus as the drug effects take hold, which then leads to changing microbiology.

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