The impact of gut microbial composition on response to neoadjuvant chemotherapy (NACT) in early-stage triple negative breast cancer (TNBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 590-590
Author(s):  
Nour Abuhadra ◽  
Chia-Chi Chang ◽  
Clinton Yam ◽  
Jason B White ◽  
Elizabeth Ravenberg ◽  
...  

590 Background: The impact of gut microbiome on tumor biology, progression and response to immunotherapy has been shown across cancer types. However, there is little known about the impact of gut microbial composition on response to chemotherapy. We have previously shown that the gut microbiome remains unaltered during NACT in a cohort of 32 patients. Here we investigate the association between gut microbiome and response to NACT in a larger cohort of early-stage TNBC. Methods: Longitudinal fecal samples were collected from 85 patients with newly-diagnosed, early-stage TNBC patients enrolled in the ARTEMIS trial (NCT02276443). Patients all received standard NACT with adriamycin/cyclophosphamide (AC); volumetric change was assessed using ultrasound and patients with < 70% volumetric reduction (VR) after 4 cycles of AC were recommended to receive targeted therapy in addition to standard NACT to improve response rates. We performed 16S sequencing on bacterial genomic DNA extracted from 85 pre-AC fecal samples using the 2x250 bp paired-end read protocol. Quality-filtered sequences were clustered into Operational Taxonomic Units and classified using Mothur method with the Silva database version 138. For differential taxa-based univariate analysis, abundant microbiome taxa at species, genus, family, class, and order levels were analyzed using DESeq2 after logit transformation. Alpha-diversity indices within group categories were calculated using phyloseq. Microbial alpha diversity (within-sample diversity) was measured by Simpson's reciprocal index. β-diversity was measured using weighted UniFrac distances between the groups. The association between microbiota abundance and pathologic complete response (pCR) or residual disease (RD) was assessed using DESeq2 analysis. Results: Pre-AC fecal samples from 85 patients were available for analysis. Amongst them, there were 46 patients with pCR and 39 patients with RD. There was no significant difference in alpha diversity (p = 0.8) or beta-diversity (p = 0.7) between the pCR and RD groups. However, relative to patients with RD, the gut microbiome in patients with pCR was enriched for the Bifidobacterium longum species (p = 0.03). The gut microbiome in patients with RD was enriched for Lachnospiraceae (p = 0.03) at the genus level and the Bacteroides thetaiotaomicron species (p = 0.02). Conclusions: We have demonstrated significant differences in the gut microbial composition in patients with pCR as compared to patients with RD. Further investigation in larger studies is needed to support therapeutic exploration of gut microbiome modulation in TNBC patients receiving chemotherapy such as probiotic supplementation or fecal microbiota transplant.

2021 ◽  
Author(s):  
Diana J. Zajac ◽  
Stefan J. Green ◽  
Lance A. Johnson ◽  
Steven Estus

Abstract Background: Apolipoprotein E (APOE) alleles impact pathogenesis and risk for multiple human diseases, making them primary targets for disease treatment and prevention. Previously, we and others reported an association between APOE alleles and the gut microbiome. Here, we tested whether these results are confirmed by using mice that were maintained under ideal conditions for microbiome analyses. Methods: To model human APOE alleles, this study used APOE targeted replacement (TR) mice on a C57Bl/6 background. To minimize genetic drift, APOE3 mice were crossed to APOE2 or APOE4 mice prior to the study, and the resulting heterozygous progeny crossed further to generate the study mice. To maximize environmental homogeneity, mice with mixed genotypes were housed together and used bedding from the cages was mixed and added back as a portion of new bedding. Fecal samples were obtained from mice at three-, five- and seven-months of age, and microbiota analyzed by 16S ribosomal RNA gene amplicon sequencing. APOE2/E2 and APOE2/E3 mice were categorized as APOE2, APOE3/E4 and APOE4/E4 mice were categorized as APOE4, and APOE3/E3 mice were categorized as APOE3. Linear discriminant analysis of Effect Size (LefSe) identified taxa associated with APOE status, depicted as cladograms to show phylogenetic relatedness. The influence of APOE status was tested onalpha-diversity (Shannon H index) and beta-diversity (principal coordinate analyses and PERMANOVA). Individual taxa associated with APOE status were identified by classical univariate analysis. Whether findings in the APOE mice were replicated in humans was evaluated by using published microbiome genome wide association data. Results: Cladograms revealed robust differences with APOE in male mice and limited differences in female mice. The richness and evenness (alpha-diversity) and microbial community composition (beta-diversity) of the fecal microbiome was robustly associated with APOE status in male but not female mice. Classical univariate analysis revealed individual taxa that were significantly increased or decreased with APOE, illustrating a stepwise APOE2-APOE3-APOE4 pattern of association. The Clostridia class, Clostridiales order, Ruminococacceae family and related genera increased with APOE2 status. The Erysipelotrichia phylogenetic branch increased with APOE4 status, a finding that extended to humans.Conclusions: In this study wherein mice were maintained in an ideal fashion for microbiome studies, gut microbiome profiles were strongly and significantly associated with APOE status in male APOE-TR mice. Erysipelotrichia in particular appears to increase with APOE4 in both mice and humans. Further evaluation of these findings in humans, as well as studies evaluating the impact of the APOE-associated microbiota on disease-relevant phenotypes, will be necessary to determine if alterations in the gut microbiome represents a novel mechanism whereby APOE alleles impact disease.


2020 ◽  
Author(s):  
Eric Adams ◽  
Andrew Oliver ◽  
Alexandria Gille ◽  
Nadia Alaniz ◽  
Carolina Jamie ◽  
...  

ABSTRACTRecent research has elucidated many factors which play a role in the development and composition of human microbiomes. In this study we briefly examine the microbiomes of saliva and fecal samples from 71 indigenous individuals, and chicha samples from 28 single family households in a remote community in the Ecuadorian Amazon. Fecal and saliva samples were collected at two separate time points whereas chicha samples were collected at four time points, once each day of the fermentation process. In total 324 samples were collected: 113 saliva, 108 chicha, and 103 fecal. Microbial composition and diversity were assessed using shotgun metagenome sequence data. Chicha samples were found to be nearly entirely composed of the order Lactobacillales, accounting for 90.1% of the relative abundance. Saliva samples also contained a high relative abundance of Lactobacillales (31.9%) as well as being composed of Neisseriales (12.8%), Actinomycineae (8.7%), Bacteroidales (7.0%), Clostridiales (6.8%), Micrococcineae (6.5%), and Pasteurellales (6.0%). Fecal samples were largely composed of the three orders Clostridiales (33.7%), Bacteroidales (21.9%), and Bifidobacteriales (16.5%). Comparison of α-diversity, as calculated by Shannon’s Diversity Index, in mothers and their offspring showed no significant difference between the two groups in either fecal or saliva samples. Comparison of β-diversity in fecal and saliva samples, as calculated by the Bray-Curtis Dissimilarity measure, within household units and between differing households showed that members of the same household were significantly less dissimilar to each other than to members of other households in the community. Average microbiome composition for individuals within fecal and saliva samples was assessed to determine the impact of an individual’s household on the composition of their microbiome. Household was determined to have a significant impact on both fecal and oral microbiome compositions.


2021 ◽  
Vol 9 (2) ◽  
pp. 183
Author(s):  
Xuehua Ma ◽  
Yi Zhou ◽  
Luyi Yang ◽  
Jianfeng Tong

Rapid development of the economy increased marine litter around Zhoushan Island. Social-ecological scenario studies can help to develop strategies to adapt to such change. To investigate the present situation of marine litter pollution, a stratified random sampling (StRS) method was applied to survey the distribution of marine coastal litters around Zhoushan Island. A univariate analysis of variance was conducted to access the amount of litter in different landforms that include mudflats, artificial and rocky beaches. In addition, two questionnaires were designed for local fishermen and tourists to provide social scenarios. The results showed that the distribution of litter in different landforms was significantly different, while the distribution of litter in different sampling points had no significant difference. The StRS survey showed to be a valuable method for giving a relative overview of beach litter around Zhoushan Island with less effort in a future survey. The questionnaire feedbacks helped to understand the source of marine litter and showed the impact on the local environment and economy. Based on the social-ecological scenarios, governance recommendations were provided in this paper.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 876-877
Author(s):  
W. Zhu ◽  
T. De Silva ◽  
L. Eades ◽  
S. Morton ◽  
S. Ayoub ◽  
...  

Background:Telemedicine was widely utilised to complement face-to-face (F2F) care in 2020 during the COVID-19 pandemic, but the impact of this on patient care is poorly understood.Objectives:To investigate the impact of telemedicine during COVID-19 on outpatient rheumatology services.Methods:We retrospectively audited patient electronic medical records from rheumatology outpatient clinics in an urban tertiary rheumatology centre between April-May 2020 (telemedicine cohort) and April-May 2019 (comparator cohort). Differences in age, sex, primary diagnosis, medications, and proportion of new/review appointments were assessed using Mann-Whitney U and Chi-square tests. Univariate analysis was used to estimate associations between telemedicine usage and the ability to assign a diagnosis in patients without a prior rheumatological diagnosis, the frequency of changes to immunosuppression, subsequent F2F review, planned admissions or procedures, follow-up phone calls, and time to next appointment.Results:3,040 outpatient appointments were audited: 1,443 from 2019 and 1,597 from 2020. There was no statistically significant difference in the age, sex, proportion of new/review appointments, or frequency of immunosuppression use between the cohorts. Inflammatory arthritis (IA) was a more common diagnosis in the 2020 cohort (35.1% vs 31%, p=0.024). 96.7% (n=1,444) of patients seen in the 2020 cohort were reviewed via telemedicine. In patients without an existing rheumatological diagnosis, the odds of making a diagnosis at the appointment were significantly lower in 2020 (28.6% vs 57.4%; OR 0.30 [95% CI 0.16-0.53]; p<0.001). Clinicians were also less likely to change immunosuppressive therapy in 2020 (22.6% vs 27.4%; OR 0.78 [95% CI 0.65-0.92]; p=0.004). This was mostly driven by less de-escalation in therapy (10% vs 12.6%; OR 0.75 [95% CI 0.59-0.95]; p=0.019) as there was no statistically significant difference in the escalation or switching of immunosuppressive therapies. There was no significant difference in frequency of follow-up phone calls, however, patients seen in 2020 required earlier follow-up appointments (p<0.001). There was also no difference in unplanned rheumatological presentations but significantly fewer planned admissions and procedures in 2020 (1% vs 2.6%, p=0.002). Appointment non-attendance reduced in 2020 to 6.5% from 10.9% in 2019 (OR 0.57 [95% CI 0.44-0.74]; p<0.001), however the odds of discharging a patient from care were significantly lower in 2020 (3.9% vs 6%; OR 0.64 [95% CI 0.46-0.89]; p=0.008), although there was no significance when patients who failed to attend were excluded. Amongst patients seen via telemedicine in 2020, a subsequent F2F appointment was required in 9.4%. The predictors of needing a F2F review were being a new patient (OR 6.28 [95% CI 4.10-9.64]; p<0.001), not having a prior rheumatological diagnosis (OR 18.43 [95% CI: 2.35-144.63]; p=0.006), or having a diagnosis of IA (OR 2.85 [95% CI: 1.40-5.80]; p=0.004) or connective tissue disease (OR 3.22 [95% CI: 1.11-9.32]; p=0.031).Conclusion:Most patients in the 2020 cohort were seen via telemedicine. Telemedicine use during the COVID-19 pandemic was associated with reduced clinic non-attendance, but with diagnostic delay, reduced likelihood of changing existing immunosuppressive therapy, earlier requirement for review, and lower likelihood of discharge. While the effects of telemedicine cannot be differentiated from changes in practice related to other aspects of the pandemic, they suggest that telemedicine may have a negative impact on the timeliness of management of rheumatology patients.Disclosure of Interests:None declared.


Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 463
Author(s):  
Mariusz Sikora ◽  
Albert Stec ◽  
Magdalena Chrabaszcz ◽  
Aleksandra Knot ◽  
Anna Waskiel-Burnat ◽  
...  

(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective of this study was to synthesize current data on the gut microbial composition in psoriasis. (2) Methods: We conducted a systematic review of studies investigating intestinal microbiome in psoriasis, using the PRISMA checklist. We searched MEDLINE, EMBASE, and Web of Science databases for relevant published articles (2000–2020). (3) Results: All of the 10 retrieved studies reported alterations in the gut microbiome in patients with psoriasis. Eight studies assessed alpha- and beta-diversity. Four of them reported a lack of change in alpha-diversity, but all confirmed significant changes in beta-diversity. At the phylum-level, at least two or more studies reported a lower relative abundance of Bacteroidetes, and higher Firmicutes in psoriasis patients versus healthy controls. (4) Conclusions: There is a significant association between alterations in gut microbial composition and psoriasis; however, there is high heterogeneity between studies. More unified methodological standards in large-scale studies are needed to understand microbiota’s contribution to psoriasis pathogenesis and its modulation as a potential therapeutic strategy.


Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 180
Author(s):  
Negash Kabtimer Bereded ◽  
Getachew Beneberu Abebe ◽  
Solomon Workneh Fanta ◽  
Manuel Curto ◽  
Herwig Waidbacher ◽  
...  

The gut microbiota of fishes is known to play an essential role in diverse aspects of host biology. The gut microbiota of fish is affected by various environmental parameters, including temperature changes, salinity and diet. Studies of effect of environment on gut microbiota enables to have a further understanding of what comprises a healthy microbiota under different environmental conditions. However, there is insufficient understanding regarding the effects of sampling season and catching site (wild and aquaculture) on the gut microbiota of Nile tilapia. This study characterised gut microbial composition and diversity from samples collected from Lake Tana and the Bahir Dar aquaculture facility centre using 16S rDNA Illumina MiSeq platform sequencing. Firmicutes and Fusobacteria were the most dominant phyla in the Lake Tana samples, while Proteobacteria was the most dominant in the aquaculture samples. The results of differential abundance testing clearly indicated significant differences for Firmicutes, Fusobacteria, Bacteroidetes and Cyanobacteria across sampling months. However, Proteobacteria, Chloroflexi, Fusobacteria and Cyanobacteria were significantly enriched in the comparison of samples from the Lake Tana and aquaculture centre. Significant differences were observed in microbial diversity across sampling months and between wild and captive Nile tilapia. The alpha diversity clearly showed that samples from the aquaculture centre (captive) had a higher diversity than the wild Nile tilapia samples from Lake Tana. The core gut microbiota of all samples of Nile tilapia used in our study comprised Firmicutes, Proteobacteria and Fusobacteria. This study clearly showed the impact of sampling season and catching site (wild and aquaculture) on the diversity and composition of bacterial communities associated with the gut of Nile tilapia. Overall, this is the first study on the effects of sampling season and catching site on the gut microbiota of Nile tilapia in Ethiopia. Future work is recommended to precisely explain the causes of these changes using large representative samples of Nile tilapia from different lakes and aquaculture farms.


Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3656
Author(s):  
Fokhrul Hossain ◽  
Samarpan Majumder ◽  
Justin David ◽  
Bruce A. Bunnell ◽  
Lucio Miele

Triple-negative breast cancer (TNBC) is an aggressive, molecularly heterogeneous subtype of breast cancer. Obesity is associated with increased incidence and worse prognosis in TNBC through various potential mechanisms. Recent evidence suggests that the gut microbiome plays a central role in the progression of cancer, and that imbalances or dysbiosis in the population of commensal microbiota can lead to inflammation and contribute to tumor progression. Obesity is characterized by low-grade inflammation, and gut dysbiosis is associated with obesity, chronic inflammation, and failure of cancer immunotherapy. However, the debate on what constitutes a “healthy” gut microbiome is ongoing, and the connection among the gut microbiome, obesity, and TNBC has not yet been addressed. This study aims to characterize the role of obesity in modulating the gut microbiome in a syngeneic mouse model of TNBC. 16S rRNA sequencing and metagenomic analyses were performed to analyze and annotate genus and taxonomic profiles. Our results suggest that obesity decreases alpha diversity in the gut microbiome. Metagenomic analysis revealed that obesity was the only significant factor explaining the similarity of the bacterial communities according to their taxonomic profiles. In contrast to the analysis of taxonomic profiles, the analysis of variation of functional profiles suggested that obesity status, tumor presence, and the obesity–tumor interaction were significant in explaining the variation of profiles, with obesity having the strongest correlation. The presence of tumor modified the profiles to a greater extent in obese than in lean animals. Further research is warranted to understand the impact of the gut microbiome on TNBC progression and immunotherapy.


2020 ◽  
Vol 176 (2) ◽  
pp. 253-284 ◽  
Author(s):  
Karen Chiu ◽  
Genoa Warner ◽  
Romana A Nowak ◽  
Jodi A Flaws ◽  
Wenyan Mei

Abstract Since the surge of microbiome research in the last decade, many studies have provided insight into the causes and consequences of changes in the gut microbiota. Among the multiple factors involved in regulating the microbiome, exogenous factors such as diet and environmental chemicals have been shown to alter the gut microbiome significantly. Although diet substantially contributes to changes in the gut microbiome, environmental chemicals are major contaminants in our food and are often overlooked. Herein, we summarize the current knowledge on major classes of environmental chemicals (bisphenols, phthalates, persistent organic pollutants, heavy metals, and pesticides) and their impact on the gut microbiome, which includes alterations in microbial composition, gene expression, function, and health effects in the host. We then discuss health-related implications of gut microbial changes, which include changes in metabolism, immunity, and neurological function.


2019 ◽  
Vol 8 (1) ◽  
pp. 60
Author(s):  
Mohd Baasir Gaisawat ◽  
Chad W. MacPherson ◽  
Julien Tremblay ◽  
Amanda Piano ◽  
Michèle M. Iskandar ◽  
...  

Clostridium (C.) difficile-infection (CDI), a nosocomial gastrointestinal disorder, is of growing concern due to its rapid rise in recent years. Antibiotic therapy of CDI is associated with disrupted metabolic function and altered gut microbiota. The use of probiotics as an adjunct is being studied extensively due to their potential to modulate metabolic functions and the gut microbiota. In the present study, we assessed the ability of several single strain probiotics and a probiotic mixture to change the metabolic functions of normal and C. difficile-infected fecal samples. The production of short-chain fatty acids (SCFAs), hydrogen sulfide (H2S), and ammonia was measured, and changes in microbial composition were assessed by 16S rRNA gene amplicon sequencing. The C. difficile-infection in fecal samples resulted in a significant decrease (p < 0.05) in SCFA and H2S production, with a lower microbial alpha diversity. All probiotic treatments were associated with significantly increased (p < 0.05) levels of SCFAs and restored H2S levels. Probiotics showed no effect on microbial composition of either normal or C. difficile-infected fecal samples. These findings indicate that probiotics may be useful to improve the metabolic dysregulation associated with C. difficile infection.


Microbiome ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Alicia Moreno-Sabater ◽  
Gaelle Autaa ◽  
Delphine Sterlin ◽  
Amenie Jerbi ◽  
Remy Villette ◽  
...  

Abstract Background Interest for the study of gut mycobiota in relation with human health and immune homeostasis has increased in the last years. From this perspective, new tools to study the immune/fungal interface are warranted. Systemic humoral immune responses could reflect the dynamic relationships between gut mycobiota and immunity. Using a novel flow cytometry technology (Fungi-Flow) to determine immunoglobulin (Ig) responses to fungi, we studied the relationships between gut mycobiota and systemic humoral anti-commensal immunity. Results The Fungi-Flow method allows a sensitive and specific measurement of systemic IgG responses against 17 commensal and environmental fungi from the two main divisions; Ascomycota and Basidiomycota. IgG responses exhibited a high inter-individual variability. Anti-commensal IgG responses were contrasted with the relative abundance, alpha-diversity, and intra-genus richness of fungal species in gut mycobiota of twenty healthy donors. Categorization of gut mycobiota composition revealed two differentiated fungal ecosystems. Significant difference of anti-Saccharomyces systemic IgG responses were observed in healthy donors stratified according to the fungal ecosystem colonizing their gut. A positive and significant correlation was observed between the variety of IgG responses against fungal commensals and intestinal alpha-diversity. At the level of intra-genus species richness, intense IgG responses were associated with a low intra-genus richness for known pathobionts, but not commensals. Conclusions Fungi-Flow allows an easy and reliable measure of personalized humoral responses against commensal fungi. Combining sequencing technology with our novel Fungi-Flow immunological method, we propose that there are at least two defined ecosystems in the human gut mycobiome associated with systemic humoral responses. Fungi-Flow opens new opportunities to improve our knowledge about the impact of mycobiota in humoral anti-commensal immunity and homeostasis.


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