Prospective correlation between the patient microbiome with response to and development of immune-mediated adverse effects to immunotherapy in lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21024-e21024
Author(s):  
Justin Chau ◽  
Meeta Yadav ◽  
Ben Liu ◽  
Muhammad Furqan ◽  
Qun Dai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gut Microbiota ◽  
Treatment Response ◽  
Gut Microbiome ◽  
Operational Taxonomic Unit ◽  
Geographic Region ◽  
Organ Function ◽  
Immune Mediated ◽  
Α Diversity ◽  
Clinical Trial Information

e21024 Background: Though the gut microbiome has been associated with immunotherapy (ICI) efficacy in certain cancers, similar correlations between microbiomes at other body sites with treatment response and immune related adverse events (irAEs) in lung cancer (LC) patients receiving ICIs have not been made. We designed a prospective cohort study conducted from 2018-2020 at a single-center academic institution to assess for correlations between the microbiome in various body sites with treatment response and development of irAEs in LC patients treated with ICIs. Methods: Patients with histopathologically confirmed, unresectable/advanced/metastatic LC planned to undergo ICI-based therapy were enrolled between September 2018 and June 2019. Patients must have had measurable disease, ECOG 0-2, and good organ function to be included. Data was collected for analysis from January 2019 to October 2020. Nasal, buccal and gut microbiome samples were obtained prior to ICI initiation, at development of irAEs, improvement of irAEs to grade 1 or less, and at disease progression. 16S rRNA sequenced data was mapped to the SILVA 13.2 database; operational taxonomic unit clusters were analyzed using MicrobiomeAnalyst and METAGENassist. Results: 37 patients were enrolled, and 34 patients were evaluable for this report. 32 healthy controls (HC) from the same geographic region were included to compare baseline gut microbiota. Compared to HC, LC gut microbiota exhibited significantly lower α-diversity. The gut microbiome of patients who did not suffer irAEs were found to have relative enrichment of Bifidobacterium ( p = 0.001) and Desulfovibrio ( p = 0.0002). Responders to combined chemoimmunotherapy exhibited increased Clostridiales ( p = 0.018) but reduced Rikenellaceae ( p = 0.016). In responders to chemoimmunotherapy we also observed enrichment of Finegoldia in nasal microbiome, and increased Megasphaera but reduced Actinobacillus in buccal samples. Longitudinal samples exhibited a trend of α-diversity and certain microbial changes during the development and resolution of irAEs. Conclusions: This pilot study identified significant differences in the gut microbiome between HC and LC patients, and correlates specific bacterial genera to ICI response and irAEs in LC. In addition, it suggests potential predictive utility in nasal and buccal microbiomes, warranting further validation with a larger cohort and mechanistic dissection using preclinical models. Clinical trial information: NCT03688347.

scholarly journals Prospective correlation between the patient microbiome with response to and development of immune-mediated adverse effects to immunotherapy in lung cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Justin Chau ◽  
Meeta Yadav ◽  
Ben Liu ◽  
Muhammad Furqan ◽  
Qun Dai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Gut Microbiota ◽  
Treatment Response ◽  
Gut Microbiome ◽  
Geographic Region ◽  
Organ Function ◽  
Predictive Utility ◽  
Immune Mediated ◽  
Α Diversity

Abstract Background Though the gut microbiome has been associated with efficacy of immunotherapy (ICI) in certain cancers, similar findings have not been identified for microbiomes from other body sites and their correlation to treatment response and immune related adverse events (irAEs) in lung cancer (LC) patients receiving ICIs. Methods We designed a prospective cohort study conducted from 2018 to 2020 at a single-center academic institution to assess for correlations between the microbiome in various body sites with treatment response and development of irAEs in LC patients treated with ICIs. Patients must have had measurable disease, ECOG 0–2, and good organ function to be included. Data was collected for analysis from January 2019 to October 2020. Patients with histopathologically confirmed, advanced/metastatic LC planned to undergo immunotherapy-based treatment were enrolled between September 2018 and June 2019. Nasal, buccal and gut microbiome samples were obtained prior to initiation of immunotherapy +/− chemotherapy, at development of adverse events (irAEs), and at improvement of irAEs to grade 1 or less. Results Thirty-seven patients were enrolled, and 34 patients were evaluable for this report. 32 healthy controls (HC) from the same geographic region were included to compare baseline gut microbiota. Compared to HC, LC gut microbiota exhibited significantly lower α-diversity. The gut microbiome of patients who did not suffer irAEs were found to have relative enrichment of Bifidobacterium (p = 0.001) and Desulfovibrio (p = 0.0002). Responders to combined chemoimmunotherapy exhibited increased Clostridiales (p = 0.018) but reduced Rikenellaceae (p = 0.016). In responders to chemoimmunotherapy we also observed enrichment of Finegoldia in nasal microbiome, and increased Megasphaera but reduced Actinobacillus in buccal samples. Longitudinal samples exhibited a trend of α-diversity and certain microbial changes during the development and resolution of irAEs. Conclusions This pilot study identifies significant differences in the gut microbiome between HC and LC patients, and their correlation to treatment response and irAEs in LC. In addition, it suggests potential predictive utility in nasal and buccal microbiomes, warranting further validation with a larger cohort and mechanistic dissection using preclinical models. Trial registration ClinicalTrials.gov, NCT03688347. Retrospectively registered 09/28/2018.

scholarly journals Role of lung and gut microbiota on lung cancer pathogenesis

2021 ◽  
Author(s):  
Yue Zhao ◽  
Yuxia Liu ◽  
Shuang Li ◽  
Zhaoyun Peng ◽  
Xiantao Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gut Microbiota ◽  
Cancer Progression ◽  
Gut Microbiome ◽  
Intestinal Flora ◽  
Inflammatory Factors ◽  
Cancer Pathogenesis ◽  
Research Findings ◽  
Relationship Of

Abstract Background Lung cancer is the leading cause of cancer-related deaths worldwide (Ferlay et al., Int J Cancer 136:E359–386, 2015). In addition, lung cancer is associated with the highest mortality among all cancer types (Wu et al., Exp Ther Med 16:3004–3010, 2018). Previous studies report that microbiota play an important role in lung cancer. Notably, changes in lung and gut microbiota, are associated with progression of lung cancer. Several studies report that lung and gut microbiome promote lung cancer initiation and development by modulating metabolic pathways, inhibiting the function of immune cells, and producing pro-inflammatory factors. In addition, some factors such as microbiota dysbiosis, affect production of bacteriotoxins, genotoxicity and virulence effect, therefore, they play a key role in cancer progression. These findings imply that lung and gut microbiome are potential markers and targets for lung cancer. However, the role of microbiota in development and progression of lung cancer has not been fully explored. Purpose The aim of this study was to systemically review recent research findings on relationship of lung and gut microbiota with lung cancer. In addition, we explored gut–lung axis and potential mechanisms of lung and gut microbiota in modulating lung cancer progression. Conclusion Pulmonary and intestinal flora influence the occurrence, development, treatment and prognosis of lung cancer, and will provide novel strategies for prevention, diagnosis, and treatment of lung cancer.

scholarly journals Distinct composition and metabolic functions of human gut microbiota are associated with cachexia in lung cancer patients

2021 ◽  
Author(s):  
Yueqiong Ni ◽  
Zoltan Lohinai ◽  
Yoshitaro Heshiki ◽  
Balazs Dome ◽  
Judit Moldvay ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gut Microbiota ◽  
Cancer Patients ◽  
Gut Microbiome ◽  
Human Gut ◽  
Microbial Composition ◽  
Shotgun Metagenomics ◽  
Lung Cancer Patients ◽  
Microbial Species ◽  
Functional Pathways

AbstractCachexia is associated with decreased survival in cancer patients and has a prevalence of up to 80%. The etiology of cachexia is poorly understood, and limited treatment options exist. Here, we investigated the role of the human gut microbiome in cachexia by integrating shotgun metagenomics and plasma metabolomics of 31 lung cancer patients. The cachexia group showed significant differences in the gut microbial composition, functional pathways of the metagenome, and the related plasma metabolites compared to non-cachectic patients. Branched-chain amino acids (BCAAs), methylhistamine, and vitamins were significantly depleted in the plasma of cachexia patients, which was also reflected in the depletion of relevant gut microbiota functional pathways. The enrichment of BCAAs and 3-oxocholic acid in non-cachectic patients were positively correlated with gut microbial species Prevotella copri and Lactobacillus gasseri, respectively. Furthermore, the gut microbiota capacity for lipopolysaccharides biosynthesis was significantly enriched in cachectic patients. The involvement of the gut microbiome in cachexia was further observed in a high-performance machine learning model using solely gut microbial features. Our study demonstrates the links between cachectic host metabolism and specific gut microbial species and functions in a clinical setting, suggesting that the gut microbiota could have an influence on cachexia with possible therapeutic applications.

Excellent treatment response with pembrolizumab in a lung cancer patient who developed immune-mediated acute motor/sensory axonal polyneuropathy

Lung Cancer ◽  
2018 ◽  
Vol 120 ◽  
pp. 149-151 ◽  
Author(s):  
Chih-Chieh Yen ◽  
Hui-Chen Su ◽  
Chang-Yao Chu ◽  
Shi-Jie Lai ◽  
Jing-Jou Yan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patient ◽  
Treatment Response ◽  
Lung Cancer Patient ◽  
Axonal Polyneuropathy ◽  
Immune Mediated

scholarly journals Contrasting patterns of bacterial communities in the rearing water and gut of Penaeus vannamei in response to exogenous glucose addition

2022 ◽  
Author(s):  
Lei Huang ◽  
Haipeng Guo ◽  
Zidan Liu ◽  
Chen Chen ◽  
Kai Wang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Bacterial Communities ◽  
Carbon Sources ◽  
Operational Taxonomic Unit ◽  
Diversity Indices ◽  
Response Patterns ◽  
Interspecies Interactions ◽  
Glucose Addition ◽  
Growth And Survival ◽  
Α Diversity

AbstractSupplementing exogenous carbon sources is a practical approach to improving shrimp health by manipulating the microbial communities of aquaculture systems. However, little is known about the microbiological processes and mechanisms of these systems. Here, the effects of glucose addition on shrimp growth performance and bacterial communities of the rearing water and the shrimp gut were investigated to address this knowledge gap. The results showed that glucose addition significantly improved the growth and survival of shrimp. Although the α-diversity indices of both bacterioplankton communities and gut microbiota were significantly decreased by adding glucose, both bacterial communities exhibited divergent response patterns to glucose addition. Glucose addition induced a dispersive bacterioplankton community but a more stable gut bacterial community. Bacterial taxa belonging to Ruegeria were significantly enriched by glucose in the guts, especially the operational taxonomic unit 2575 (OTU2575), which showed the highest relative importance to the survival rate and individual weight of shrimp, with the values of 43.8 and 40.6%, respectively. In addition, glucose addition increased the complexity of interspecies interactions within gut bacterial communities and the network nodes from Rhodobacteraceae accounted for higher proportions and linked more with the nodes from other taxa in the glucose addition group than that in control. These findings suggest that glucose addition may provide a more stable gut microbiota for shrimp by increasing the abundance of certain bacterial taxa, such as Ruegeria.

scholarly journals Distinct gut microbial communities and metabolic functions are associated with cachexia in lung cancer patients

2020 ◽  
Author(s):  
Yueqiong Ni ◽  
Zoltan Lohinai ◽  
Yoshitaro Heshiki ◽  
Balazs Dome ◽  
Judit Moldvay ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gut Microbiota ◽  
Cancer Patients ◽  
Clinical Setting ◽  
Gut Microbiome ◽  
Microbial Composition ◽  
Shotgun Metagenomics ◽  
Lung Cancer Patients ◽  
Microbial Species ◽  
Functional Pathways

Abstract Background Cachexia is associated with decreased survival in cancer patients and has a prevalence of up to 80%. The etiology of cachexia is poorly understood, and limited treatment options exist. Here, we investigated the role of the human gut microbiome in the clinical setting by integrating shotgun metagenomics and plasma metabolomics of 38 lung cancer patients, with known cachexia status. Results The cachexia group showed significant differences in the gut microbial composition, functional pathways of the metagenome, and the related plasma metabolites compared to non-cachectic patients. Branched-chain amino acids (BCAAs), methylhistamine, as well as vitamins, were significantly depleted in the plasma of cachexia patients, which was also reflected in the depletion of relevant gut microbiota functional pathways. The enrichment of plasma BCAAs and 3-oxocholic acid in non-cachectic patients were positively correlated with the gut microbial species Prevotella copri and Lactobacillus gasseri, respectively. Furthermore, the gut microbiota capacity for lipopolysaccharides biosynthesis was significantly enriched in the cancer cachectic patients. The involvement of gut microbiome in cachexia was further observed in a high-performance machine learning model that uses solely gut microbial taxonomic and pathway features to differentiate cachectic from non-cachectic cancer patients. Conclusions Our study demonstrates the links between host metabolism and specific gut microbial species and functions in a clinical setting, suggesting that the gut microbiota could have an influence on cachexia with possible future therapeutic applications.

scholarly journals Analyzing Type 2 Diabetes Associations with the Gut Microbiome in Individuals from Two Ethnic Backgrounds Living in the Same Geographic Area

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3289
Author(s):  
Manon Balvers ◽  
Mélanie Deschasaux ◽  
Bert-Jan van den Born ◽  
Koos Zwinderman ◽  
Max Nieuwdorp ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
South Asian ◽  
Gut Microbiome ◽  
Geographical Area ◽  
Microbiota Composition ◽  
Α Diversity ◽  
Functional Pathways ◽  
Gut Microbiota Composition

It is currently unknown whether associations between gut microbiota composition and type 2 diabetes (T2D) differ according to the ethnic background of individuals. Thus, we studied these associations in participants from two ethnicities characterized by a high T2D prevalence and living in the same geographical area, using the Healthy Life In Urban Settings (HELIUS) study. We included 111 and 128 T2D participants on metformin (Met-T2D), 78 and 49 treatment-naïve T2D (TN-T2D) participants, as well as a 1:1 matched group of healthy controls from, respectively, African Surinamese and South-Asian Surinamese descent. Fecal microbiome profiles were obtained through 16S rRNA gene sequencing. Univariate and machine learning analyses were used to explore the associations between T2D and the composition and function of the gut microbiome in both ethnicities, comparing Met-T2D and TN-T2D participants to their respective healthy control. We found a lower α-diversity for South-Asian Surinamese TN-T2D participants but no significant associations between TN-T2D status and the abundance of bacterial taxa or functional pathways. In African Surinamese participants, we did not find any association between TN-T2D status and the gut microbiome. With respect to Met-T2D participants, we identified several bacterial taxa and functional pathways with a significantly altered abundance in both ethnicities. More alterations were observed in South-Asian Surinamese. Some altered taxa and pathways observed in both ethnicities were previously related to metformin use. This included a strong negative association between the abundance of Romboutsia and Met-T2D status. Other bacterial taxa were consistent with previous observations in T2D, including reduced butyrate producers such as Anaerostipes hadrus. Hence, our results highlighted both shared and unique gut microbial biomarkers of Met-T2D in individuals from different ethnicities but living in the same geographical area. Future research using higher-resolution shotgun sequencing is needed to clarify the role of ethnicity in the association between T2D and gut microbiota composition.

scholarly journals The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiangjun Liu ◽  
Ye Cheng ◽  
Dan Zang ◽  
Min Zhang ◽  
Xiuhua Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Checkpoint Inhibitors ◽  
Fecal Microbiota ◽  
Immune Homeostasis ◽  
Gut Dysbiosis ◽  
Underlying Mechanisms ◽  
And Function

The influence of microbiota on host health and disease has attracted adequate attention, and gut microbiota components and microbiota-derived metabolites affect host immune homeostasis locally and systematically. Some studies have found that gut dysbiosis, disturbance of the structure and function of the gut microbiome, disrupts pulmonary immune homeostasis, thus leading to increased disease susceptibility; the gut-lung axis is the primary cross-talk for this communication. Gut dysbiosis is involved in carcinogenesis and the progression of lung cancer through genotoxicity, systemic inflammation, and defective immunosurveillance. In addition, the gut microbiome harbors the potential to be a novel biomarker for predicting sensitivity and adverse reactions to immunotherapy in patients with lung cancer. Probiotics and fecal microbiota transplantation (FMT) can enhance the efficacy and depress the toxicity of immune checkpoint inhibitors by regulating the gut microbiota. Although current studies have found that gut microbiota closely participates in the development and immunotherapy of lung cancer, the mechanisms require further investigation. Therefore, this review aims to discuss the underlying mechanisms of gut microbiota influencing carcinogenesis and immunotherapy in lung cancer and to provide new strategies for governing gut microbiota to enhance the prevention and treatment of lung cancer.

scholarly journals Gut Microbiota of Great Spotted Cuckoo Nestlings is a Mixture of Those of Their Foster Magpie Siblings and of Cuckoo Adults

Genes ◽  
2018 ◽  
Vol 9 (8) ◽  
pp. 381 ◽  
Author(s):  
Magdalena Ruiz-Rodríguez ◽  
Manuel Martín-Vivaldi ◽  
Manuel Martínez-Bueno ◽  
Juan José Soler
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Natural Populations ◽  
Microbiome Composition ◽  
Operational Taxonomic Units ◽  
Sequencing Technologies ◽  
Genetic Components ◽  
Α Diversity ◽  
Host Genetic ◽  
Diversity Estimates

Diet and host genetic or evolutionary history are considered the two main factors determining gut microbiota of animals, although studies are scarce in natural populations. The system of great spotted cuckoos (Clamator glandarius) parasitizing magpies (Pica pica) is ideal to study both effects since magpie adults feed cuckoo and magpie nestlings with the same diet and, consequently, differences in gut microbiota of nestlings of these two species will mainly reflect the importance of genetic components. Moreover, the diet of adults and of nestling cuckoos drastically differ from each other and, thus, differences and similarities in their microbiotas would respectively reflect the effect of environmental and genetic factors. We used next-generation sequencing technologies to analyze the gut microbiota of cuckoo adults and nestlings and of magpie nestlings. The highest α-diversity estimates appeared in nestling cuckoos and the lowest in nestling magpies. Moreover, despite the greatest differences in the microbiome composition of magpies and cuckoos of both ages, cuckoo nestlings harbored a mixture of the Operational Taxonomic Units (OTUs) present in adult cuckoos and nestling magpies. We identified the bacterial taxa responsible for such results. These results suggest important phylogenetic components determining gut microbiome of nestlings, and that diet might be responsible for similarities between gut microbiome of cuckoo and magpie nestlings that allow cuckoos to digest food provided by magpie adults.

scholarly journals Detangling Diet from Obesity Effects on the Gut Microbiome and Metabolic Parameters Using a Non-Human Primate Model

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1583-1583
Author(s):  
Carol Shively ◽  
Kenysha Clear ◽  
Katherine Cook
Keyword(s):  
Gut Microbiota ◽  
Body Fat ◽  
Gut Microbiome ◽  
Western Diet ◽  
Metabolic Parameters ◽  
Primate Model ◽  
Body Adiposity ◽  
Α Diversity ◽  
The Impact ◽  
Human Primate

Abstract Objectives Poor diet and obesity often go hand-in-hand and are difficult to discern which variable is the major driver of the gut microbiome. The objective of this study was to determine the impact of obesity within dietary exposures on the gut microbiome and metabolic parameters using a non-human primate model. Methods Female M. fasicularis monkeys were fed a Western or Mediterranean diet for 2.5 years. We performed metagenomics sequencing on fecal samples obtained at 26 months. DNA was isolated from feces using Qiagen PowerSoil DNA extraction kit and metagenomics sequencing was performed for multikingdom microbiome analysis. DEXA scans for body adiposity and metabolic profiling were measured in each subject before the end of the study. Subjects were grouped by body fat composition (Lean (≤10% body fat) or Overweight/Obese (≥20% body fat)) and the impact of diet and adiposity was determine on the gut microbiome. Gut microbiota populations were correlated with metabolic parameters. Results Diet is the main determinant on gut microbiome α-diversity. Obesity had no significant outcome on Shannon diversity. Obesity within each dietary pattern can influence certain gut microbes. Lean Mediterranean diet-fed animals had significantly higher L. animals and C. comes that overweight animals fed the same diet. Obese Western diet-fed animals displayed elevated proportional abundance of S. infantarius and R. chanpaneliensis that lean Western diet-fed animals. Independent of adiposity, Western diet consumption lead to two distinct microbiome populations; P. copri high and P. copri low. P. copriHIGH displayed reduced α-diversity, increased abundance of other Prevotella species (P. stercorea, P. brevis, and P. bryantii), and increased F. prausnitzii. P. copri negatively correlated with α-diversity. P. copriLOW displayed increased proportional abundance of E. siraeum. Gut E. siraeum populations positively correlated with plasma HDL cholesterol levels. Conclusions Our data indicates that diet is a potent regulator of the gut microbiome, while body adiposity can subtly shift specific gut microbiota taxa within subjects fed a specific dietary pattern. Moreover, our data indicates at a sub-group of metabolically healthier subjects on a Western diet characterized by low P. copri microbiota abundance. Funding Sources NIH and DOD BCRP.

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