scholarly journals Adaptive changes in the gut microbiome during standard-of-care chemoradiotherapy for gynecologic cancers

2020 ◽  
Author(s):  
Molly B. El Alam ◽  
Travis T. Sims ◽  
Ramez Kouzy ◽  
Greyson W. G. Biegert ◽  
Joseph Abi Jaoude ◽  
...  

ABSTRACTBackgroundA diverse and abundant gut microbiome can improve cancer patients’ treatment response; however, the effect of pelvic chemoradiotherapy (CRT) on gut diversity and composition is unclear. The purpose of this prospective study was to identify changes in the diversity and composition of the gut microbiome during and after pelvic CRT.Materials and MethodsRectal swabs from 58 women with cervical, vaginal, or vulvar cancer from two institutions were prospectively analyzed before CRT (baseline), during CRT (weeks 1, 3, and 5), and at first follow-up (week 12) using 16Sv4 rRNA gene sequencing of the V4 hypervariable region of the bacterial 16S rRNA marker gene. Observed operational taxonomic units (OTUs; representative of richness) and Shannon, Simpson, Inverse Simpson, and Fisher diversity indices were used to characterize alpha (within-sample) diversity. Changes over time were assessed using a paired t-test, repeated measures ANOVA, and linear mixed modeling. Compositional changes in specific bacteria over time were evaluated using linear discriminant analysis effect size.ResultsGut microbiome richness and diversity levels continually decreased throughout CRT (mean Shannon diversity index, 2.52 vs. 2.91; all P <0.01), but were at or near baseline levels in 60% of patients by week 12. Patients with higher gut diversity at baseline had the steepest decline in gut microbiome diversity. Gut microbiome composition was significantly altered during CRT, with increases in Proteobacteria and decreases in Clostridiales, but adapted after CRT, with increases in Bacteroides species.ConclusionAfter CRT, the gut microbiome’s diversity tends to return to baseline levels, but its structure and composition remain significantly altered. These changes should be considered when designing studies to analyze the gut microbiome as a predictive or prognostic biomarker in patients who receive pelvic CRT for gynecologic cancers.

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247905
Author(s):  
Molly B. El Alam ◽  
Travis T. Sims ◽  
Ramez Kouzy ◽  
Greyson W. G. Biegert ◽  
Joseph A. B. I. Jaoude ◽  
...  

Background A diverse and abundant gut microbiome can improve cancer patients’ treatment response; however, the effect of pelvic chemoradiotherapy (CRT) on gut diversity and composition is unclear. The purpose of this prospective study was to identify changes in the diversity and composition of the gut microbiome during and after pelvic CRT. Materials and methods Rectal swabs from 58 women with cervical, vaginal, or vulvar cancer from two institutions were prospectively analyzed before CRT (baseline), during CRT (weeks 1, 3, and 5), and at first follow-up (week 12) using 16Sv4 rRNA gene sequencing of the V4 hypervariable region of the bacterial 16S rRNA marker gene. 42 of these patients received antibiotics during the study period. Observed operational taxonomic units (OTUs; representative of richness) and Shannon, Simpson, Inverse Simpson, and Fisher diversity indices were used to characterize alpha (within-sample) diversity. Changes over time were assessed using a paired t-test, repeated measures ANOVA, and linear mixed modeling. Compositional changes in specific bacteria over time were evaluated using linear discriminant analysis effect size. Results Gut microbiome richness and diversity levels continually decreased throughout CRT (mean Shannon diversity index, 2.52 vs. 2.91; all P <0.01), but were at or near baseline levels in 60% of patients by week 12. Patients with higher gut diversity at baseline had the steepest decline in gut microbiome diversity. Gut microbiome composition was significantly altered during CRT, with increases in Proteobacteria and decreases in Clostridiales, but adapted after CRT, with increases in Bacteroides species. Conclusion After CRT, the diversity of the gut microbiomes in this population tended to return to baseline levels by the 12 week follow-up period, but structure and composition remained significantly altered. These changes should be considered when designing studies to analyze the gut microbiome in patients who receive pelvic CRT for gynecologic cancers.


2020 ◽  
Vol 9 (11) ◽  
pp. 3687
Author(s):  
Ana F. Pereira-da-Mota ◽  
Jéssica Costa ◽  
Ana Amorim-de-Sousa ◽  
José M. González-Méijome ◽  
António Queirós

This study aimed to evaluate the effects of two months of orthokeratology (OK) treatment in the accommodative response of young adult myopes. Twenty eyes (21.8 ± 1.8 years) were fitted with the Paragon CRT® 100 LENS to treat myopia between −1.00 and −2.00 D. Low- and high-contrast visual acuity (LCDVA and HCDVA), central objective refraction, light disturbance (LD), and objective accommodative response (using the Grand Seiko WAM-5500 open-field autorefractometer coupled with a Badal system) were measured at baseline (BL) before lens wear and after 1, 15, 30, and 60 nights of OK. Refractive error correction was achieved during the first fifty days of OK lens wear, with minimal changes afterwards. LD analysis showed a transient increase followed by a reduction to baseline levels over the first 30 nights of treatment. The accommodative response was lower than expected for all target vergences in all visits (BL: 0.61 D at 1.00 D to 0.96 D at 5.00 D; 60 N: 0.36 D at 1.00 D to 0.79 D at 5.00 D). On average, the accommodative lag decreases over time with OK lens wear. However, these differences were not statistically significant (p > 0.050, repeated-measures ANOVA and Friedman test). This shows that overnight OK treatment does not affect objectively measured the accommodative response of young, low myopic eyes after two months of treatment stabilization.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1450-1450
Author(s):  
Gertraud Maskarinec ◽  
Phyllis Raquinio ◽  
Bruce Kristal ◽  
Lynne Wilkens ◽  
Adrian Franke ◽  
...  

Abstract Objectives As features of the gut microbiome may promote the development of type 2 diabetes (T2D), we examined the hypothesis that gut microbiome composition differs by glycemic/diabetes status within a subset of the Multiethnic Cohort. We also estimated the association of lipopolysaccharide-binding protein (LBP) as a measure of circulating bacterial endotoxin with T2D. This outer membrane component of gram-negative bacteria may affect glucose metabolism. Methods In 2013–16, cohort members from 5 ethnic groups completed clinic visits, questionnaires, and stool collections. Participants with self-reported T2D and/or taking medication were considered T2D cases. Those with fasting glucose &gt;125 and 100–125 mg/dL were classified as undiagnosed (UT2D) and prediabetes (PT2D). We characterized the gut microbiome through 16S rRNA gene sequencing (V1-V3). Plasma LBP was measured by ELISA. Linear regression was applied to estimate associations of gut microbiome community structure and LBP with T2D status adjusting for relevant confounders. Results Among 1756 participants (59.9–77.4 years), 315 (18%) were T2D, 158 (9%) UT2D, 518 (29%) PT2D, and 765 (44%) normoglycemic (NG). The Shannon diversity index was lower (6.30, 6.25, 6.28, 6.18; P = 0.02) and LBP was higher (26.0, 26.6, 28.6, 28.2 µg/mL; P = 0.0009) in T2D than NG participants. Of 10 phyla, Actinobacteria and Firmicutes were inversely associated with T2D status (P = 0.004). Six of 161 genera were significantly related to T2D status after Bonferroni adjustment: the abundance of Clostridium sensu stricto 1, Lachnospira, Lachnospiraceae NC2004, and Peptostreptococcaceae was lower, while Lachnospiraceae uncultured and Escherichia-Shigella were more abundant among T2D than NG participants. In general, those with PT2D and UT2D had values closer to NG than T2D individuals. Conclusions Participants with T2D showed a lower abundance of bacteria capable of fermenting plant polysaccharides and higher levels of gram-negative endotoxin-producing bacteria indicating that a less favorable pattern of gut microbiome community structure may contribute to T2D through endotoxin binding to toll-like receptors via LBP and activation of the NFkB pathway associated with chronic systemic inflammation. Funding Sources NIH grants P01CA169530, U01CA164973, P30CA071789, #UL1TR000130, R01HL140335.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4663 ◽  
Author(s):  
Shaaz Fareed ◽  
Neha Sarode ◽  
Frank J. Stewart ◽  
Aneeq Malik ◽  
Elham Laghaie ◽  
...  

Background Fecal Microbiota Transplantation (FMT) is an innovative means of treating recurrent Clostridium difficile infection (rCDI), through restoration of gut floral balance. However, there is a lack of data concerning the efficacy of FMT and its impact on the gut microbiome among pediatric patients. This study analyzes clinical outcomes and microbial community composition among 15 pediatric patients treated for rCDI via FMT. Methods This is a prospective, observational, pilot study of 15 children ≤18 years, who presented for rCDI and who met inclusion criteria for FMT at a pediatric hospital and pediatric gastroenterology clinic. Past medical history and demographics were recorded at enrollment and subsequent follow-up. Specimens of the donors’ and the patients’ pre-FMT and post-FMT fecal specimen were collected and used to assess microbiome composition via 16S rRNA gene sequencing. Results FMT successfully prevented rCDI episodes for minimum of 3 months post-FMT in all patients, with no major adverse effects. Three patients reported continued GI bleeding; however, all three also had underlying Inflammatory Bowel Disease (IBD). Our analyses confirm a significant difference between pre-and post-FMT gut microbiome profiles (Shannon diversity index), whereas no significant difference was observed between post-FMT and donor microbiome profiles. At the phyla level, post-FMT profiles showed significantly increased levels of Bacteroidetes and significantly decreased levels of Proteobacteria. Subjects with underlying IBD showed no difference in their pre-and post-FMT profiles. Conclusion The low rate of recurrence or re-infection by C. difficile, coupled with minimal adverse effects post-FMT, suggests that FMT is a viable therapeutic means to treat pediatric rCDI. Post-FMT microbiomes are different from pre-FMT microbiomes, and similar to those of healthy donors, suggesting successful establishment of a healthier microbiome.


Author(s):  
Chin-Hee Song ◽  
Nayoung Kim ◽  
Ryoung Hee Nam ◽  
Soo In Choi ◽  
Jeong Eun Yu ◽  
...  

The frequency of azoxymethane/dextran sulfate sodium (AOM/DSS)-induced carcinogenesis in male mice is higher than that in female mice. Previous studies have reported that 17β-estradiol inhibits tumorigenesis in males by modulating nuclear factor-erythroid 2-related factor 2 (Nrf2). This study aimed to investigate the changes in mouse gut microbiome composition based on sex, AOM/DSS-induced colorectal cancer (CRC), and Nrf2 genotype. The gut microbiome composition was determined by 16S rRNA gene sequencing fecal samples obtained at week 16 post-AOM administration. In terms of sex differences, our results showed that the wild-type (WT) male control mice had higher alpha diversity (i.e. Chao1, Shannon, and Simpson) than the WT female control mice. The linear discriminant analysis effect size (LEfSe) results revealed that the abundances of Akkermansia muciniphila and Lactobacillus murinus were higher in WT male control mice than in WT female controls. In terms of colon tumorigenesis, the alpha diversity of the male CRC group was lower than that of the male controls in both WT and Nrf2 KO, but did not show such changes in females. Furthermore, the abundance of A. muciniphila was higher in male CRC groups than in male controls in both WT and Nrf2 KO. The abundance of Bacteroides vulgatus was higher in WT CRC groups than in WT controls in both males and females. However, the abundance of L. murinus was lower in WT female CRC and Nrf2 KO male CRC groups than in its controls. The abundance of A. muciniphila was not altered by Nrf2 KO. In contrast, the abundances of L. murinus and B. vulgatus were changed differently by Nrf2 KO depending on sex and CRC. Interestingly, L. murinus showed negative correlation with tumor numbers in the whole colon. In addition, B. vulgatus showed positive correlation with inflammatory markers (i.e. myeloperoxidase and IL-1β levels), tumor numbers, and high-grade adenoma, especially, developed mucosal and submucosal invasive adenocarcinoma at the distal part of the colon. In conclusion, Nrf2 differentially alters the gut microbiota composition depending on sex and CRC induction.


2012 ◽  
Vol 78 (17) ◽  
pp. 6153-6160 ◽  
Author(s):  
Elizabeth A. Maga ◽  
Prerak T. Desai ◽  
Bart C. Weimer ◽  
Nguyet Dao ◽  
Dietmar Kültz ◽  
...  

ABSTRACTHuman milk contains antimicrobial factors such as lysozyme and lactoferrin that are thought to contribute to the development of an intestinal microbiota beneficial to host health. However, these factors are lacking in the milk of dairy animals. Here we report the establishment of an animal model to allow the dissection of the role of milk components in gut microbiota modulation and subsequent changes in overall and intestinal health. Using milk from transgenic goats expressing human lysozyme at 68%, the level found in human milk and young pigs as feeding subjects, the fecal microbiota was analyzed over time using 16S rRNA gene sequencing and the G2 Phylochip. The two methods yielded similar results, with the G2 Phylochip giving more comprehensive information by detecting more OTUs. Total community populations remained similar within the feeding groups, and community member diversity was changed significantly upon consumption of lysozyme milk. Levels ofFirmicutes(Clostridia) declined whereas those ofBacteroidetesincreased over time in response to the consumption of lysozyme-rich milk. The proportions of these major phyla were significantly different (P< 0.05) from the proportions seen with control-fed animals after 14 days of feeding. Within phyla, the abundance of bacteria associated with gut health (BifidobacteriaceaeandLactobacillaceae) increased and the abundance of those associated with disease (Mycobacteriaceae,Streptococcaceae,Campylobacterales) decreased with consumption of lysozyme milk. This study demonstrated that a single component of the diet with bioactivity changed the gut microbiome composition. Additionally, this model enabled the direct examination of the impact of lysozyme on beneficial microbe enrichment versus detrimental microbe reduction in the gut microbiome community.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wenqing Rao ◽  
Zheng Lin ◽  
Shuang Liu ◽  
Zhihui Zhang ◽  
Qianwen Xie ◽  
...  

Abstract Background Microbiota has been reported to play a role in cancer patients. Nevertheless, little is known about the association between alcohol consumption and resultant changes in the diversity and composition of oesophageal microbiota in oesophageal squamous cell carcinoma (ESCC). Methods We performed a hospital-based retrospective study of 120 patients with pathologically diagnosed primary ESCC. The relevant information for all study participants were collected through a detailed questionnaire. The differences in adjacent tissues between non-drinkers and drinkers were explored using 16S rRNA gene sequencing. Raw sequencing data were imported into QIIME 2 to analyse the diversity and abundance of microbiota. Linear discriminant analysis effect size (LEfSe) and unconditional logistic regression were performed to determine the bacterial taxa that were associated with drinking. Results The Shannon diversity index and Bray-Curtis distance of oesophageal microbiota were significantly different among drinkers(P < 0.05). The alcohol-related bacteria were primarily from the orders Clostridiales, Gemellales and Pasteurellales, family Clostridiaceae, Lanchnospiraceae, Helicobacteraceae, Alcaligenaceae, Bacteroidaceae, Pasteurellaceae and Gemellaceae; genus Clostridium, Helicobacter, Catonella, Bacteroides, Bacillus, Moraxella, and Bulleidia; and species B. moorei and longum (genus Bifidobacterium). In addition, the diversity and abundance of these microbiota were observed to be affected by the age, residential districts of the patients, and sampling seasons. Moreover, the higher the frequency and years of alcohol consumption, the lower was the relative abundance of genus Catonella that was observed. Conclusion Alcohol consumption is associated with alterations in both the diversity and composition the of the oesophageal microbiota in ESCC patients.


2021 ◽  
Author(s):  
Wei Huang ◽  
Chengqi Tu ◽  
Zhenghai Jin ◽  
Haoran Yang ◽  
Changyu Lu ◽  
...  

Abstract Sediment bacterial communities are a vital component of microbial communities in aquatic and terrestrial ecosystems and they play a critical role in lake wetlands. To investigate the effect of season, depth and regional environmental factors on the composition and diversity of bacterial communities in lake wetland sediments, the millions of Illumina reads (16S rRNA gene amplicons) from sediment bacterial communities in different seasons were examined using a technically consistent approach. Results from diversity index, relative abundance, principal component analysis (PCA), redundancy analysis (RDA) and linear discriminant analysis effect size (LEfSe) analysis indicated that the diversity of the bacterial community in summer was generally higher than in other seasons. Proteobacteria was the most abundant phylum in the sediment samples in different seasons (43.15%–57.41%) and different layers (39.66%–77.97%); the autumn sediments were enriched with Firmicutes (5.67%) and Chloroflexi (12.5%); in all four seasons the sediments were enriched with Betaproteobacteria (14.98%–23.45%), Gammaproteobacteria (11.98%–14.36%) and Deltaproteobacteria (8.68%–14.45%). In the bottom sediments (10–25 cm) Chloroflexi were abundant (average value 10.42%), while Bacteroidetes was the dominant phylum in the surface sediments; and redundancy analysis found that total phosphorus (TP) (P = 0.036) was the main environmental factor influencing the sediment bacterial community in different layers. This study provides a reference for further understanding the effects of seasonal changes on sediment microorganisms in lake wetlands.


mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Ryan J. Newton ◽  
Sandra L. McLellan ◽  
Deborah K. Dila ◽  
Joseph H. Vineis ◽  
Hilary G. Morrison ◽  
...  

ABSTRACT Molecular characterizations of the gut microbiome from individual human stool samples have identified community patterns that correlate with age, disease, diet, and other human characteristics, but resources for marker gene studies that consider microbiome trends among human populations scale with the number of individuals sampled from each population. As an alternative strategy for sampling populations, we examined whether sewage accurately reflects the microbial community of a mixture of stool samples. We used oligotyping of high-throughput 16S rRNA gene sequence data to compare the bacterial distribution in a stool data set to a sewage influent data set from 71 U.S. cities. On average, only 15% of sewage sample sequence reads were attributed to human fecal origin, but sewage recaptured most (97%) human fecal oligotypes. The most common oligotypes in stool matched the most common and abundant in sewage. After informatically separating sequences of human fecal origin, sewage samples exhibited ~3× greater diversity than stool samples. Comparisons among municipal sewage communities revealed the ubiquitous and abundant occurrence of 27 human fecal oligotypes, representing an apparent core set of organisms in U.S. populations. The fecal community variability among U.S. populations was significantly lower than among individuals. It clustered into three primary community structures distinguished by oligotypes from either: Bacteroidaceae, Prevotellaceae, or Lachnospiraceae/Ruminococcaceae. These distribution patterns reflected human population variation and predicted whether samples represented lean or obese populations with 81 to 89% accuracy. Our findings demonstrate that sewage represents the fecal microbial community of human populations and captures population-level traits of the human microbiome. IMPORTANCE The gut microbiota serves important functions in healthy humans. Numerous projects aim to define a healthy gut microbiome and its association with health states. However, financial considerations and privacy concerns limit the number of individuals who can be screened. By analyzing sewage from 71 cities, we demonstrate that geographically distributed U.S. populations share a small set of bacteria whose members represent various common community states within U.S. adults. Cities were differentiated by their sewage bacterial communities, and the community structures were good predictors of a city's estimated level of obesity. Our approach demonstrates the use of sewage as a means to sample the fecal microbiota from millions of people and its potential to elucidate microbiome patterns associated with human demographics.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Corrie Whisner ◽  
Kiley Vander Wyst ◽  
Megan Petrov ◽  
David McCormick ◽  
Michael Todd ◽  
...  

Abstract Objectives Nearly 10% of infants and toddlers carry excess weight for their length. Rapid weight gain (RWG; >+0.67 change in weight-for-age Z-score) and feeding practices from 0–6 months (mo) of life are strong determinants of obesity. Both RWG and feeding practices may influence the gut microbiome (GM), which in turn can affect obesity risk by increasing susceptibility to weight gain during infancy. Our goal was to evaluate differences in GM community structure at 36 months of age in relation to feeding practices and RWG in infancy. Methods Pregnant, obese Latinas (n = 36) recruited from the Special Supplemental Nutrition Program for Women, Infants, and Children program took part in a larger randomized health education trial designed to prevent infant overweight. The intervention was delivered from 0–12 mo and participants were followed until 36 mo of age. At one, 6, and 12 mo, mothers reported infant feeding practices. RWG was categorized as >0.67 positive change in weight-for-age Z-score over the first 6 months of life. Microbial DNA from feces collected at 36 mo were sequenced using primers for the 16S rRNA gene V4 region. GM diversity metrics were examined using Kruskal-Wallis and PERMANOVA comparisons, adjusted for multiple comparisons, via Qiime2. Results Of the cohort, 12 children experienced RWG in the first 6 mo of life. Within-sample species number (richness, Shannon Diversity Index: P = 0.014) and evenness (Pielou's Index: P = 0.019) were significantly lower at 3 years among children experiencing RWG in infancy. Upon comparing GM community structure (beta-diversity), exclusively breastfed infants (N = 9) formed a separate cluster from combination or formula-fed infants driven by phylogenetic diversity and species presence/absence (unweighted UniFrac: P = 0.033; Jaccard: P = 0.014). Children introduced to solid foods before (N = 30) vs. after (N = 6) 6 mo (Bray Curtis: P = 0.056; weighted UniFrac: P = 0.071). Conclusions RWG and feeding practices in the first 6 mo of life appear to shape the GM in ways that last into toddlerhood. Identifying specific microbes may provide insights for intervention to prevent RWG. How shifts in the GM influence risk for childhood and adult obesity remain an area for exploration. Funding Sources R01DK096488 and ASU Obesity Solutions, Virginia G. Piper Foundation.


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