scholarly journals Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in hepatobiliary cancers

2021 ◽  
Vol 9 (12) ◽  
pp. e003334
Author(s):  
Jinzhu Mao ◽  
Dongxu Wang ◽  
Junyu Long ◽  
Xu Yang ◽  
Jianzhen Lin ◽  
...  
Keyword(s):  
Clinical Response ◽  
Cancer Immunotherapy ◽  
Gut Microbiome ◽  
Clinical Benefit ◽  
Progression Free Survival ◽  
Metagenomic Sequencing ◽  
Microbiome Diversity ◽  
Clinical Benefit Response ◽  
Fresh Stool ◽  
The Impact

BackgroundThe gut microbiome is associated with the response to immunotherapy for different cancers. However, the impact of the gut microbiome on hepatobiliary cancers receiving immunotherapy remains unknown. This study aims to investigate the relationship between the gut microbiome and the clinical response to anti-programmed cell death protein 1 (PD-1) immunotherapy in patients with advanced hepatobiliary cancers.MethodsPatients with unresectable hepatocellular carcinoma or advanced biliary tract cancers who have progressed from first-line chemotherapy (gemcitabine plus cisplatin) were enrolled. Fresh stool samples were collected before and during anti-PD-1 treatment and analyzed with metagenomic sequencing. Significantly differentially enriched taxa and prognosis associated taxa were identified. The Kyoto Encyclopedia of Genes and Genomes database and MetaCyc database were further applied to annotate the differentially enriched taxa to explore the potential mechanism of the gut microbiome influencing cancer immunotherapy.ResultsIn total, 65 patients with advanced hepatobiliary cancers receiving anti-PD-1 treatment were included in this study. Seventy-four taxa were significantly enriched in the clinical benefit response (CBR) group and 40 taxa were significantly enriched in the non-clinical benefit (NCB) group. Among these taxa, patients with higher abundance of Lachnospiraceae bacterium-GAM79 and Alistipes sp Marseille-P5997, which were significantly enriched in the CBR group, achieved longer progression-free survival (PFS) and overall survival (OS) than patients with lower abundance. Higher abundance of Ruminococcus calidus and Erysipelotichaceae bacterium-GAM147 enriched in the CBR group was also observed in patients with better PFS. In contrast, worse PFS and OS were found in patients with higher abundance of Veillonellaceae, which was significantly enriched in the NCB group. Functional annotation indicated that the taxa enriched in the CBR group were associated with energy metabolism while the taxa enriched in the NCB group were associated with amino acid metabolism, which may modulate the clinical response to immunotherapy in hepatobiliary cancers. In addition, immunotherapy-related adverse events were affected by the gut microbiome diversity and relative abundance.ConclusionsWe demonstrate that the gut microbiome is associated with the clinical response to anti-PD-1 immunotherapy in patients with hepatobiliary cancers. Taxonomic signatures enriched in responders are effective biomarkers to predict the clinical response and survival benefit of immunotherapy, which might provide a new therapeutic target to modulate the response to cancer immunotherapy.

scholarly journals Macrofungi Cultivation in Shady Forest Areas Significantly Increases Microbiome Diversity, Abundance and Functional Capacity in Soil Furrows

2021 ◽  
Vol 7 (9) ◽  
pp. 775
Author(s):  
Dong Liu ◽  
Yanliang Wang ◽  
Peng Zhang ◽  
Fuqiang Yu ◽  
Jesús Perez-Moreno
Keyword(s):  
Functional Capacity ◽  
Metagenomic Sequencing ◽  
Mushroom Cultivation ◽  
Genome Database ◽  
Total N ◽  
Microbiome Diversity ◽  
Develop Economy ◽  
And Control ◽  
The Impact ◽  
Microbial Hotspots

Cultivating macrofungi is an important management measure to develop economy in shady forest areas; however, its effect on soil ecology, especially microbial abundance and structure, remains insufficiently studied. Herein, in a subtropical forestland, soil chemical and enzyme analyses, metagenomic sequencing and quantitative real-time PCR were employed to evaluate the impact of Stropharia rugosoannulata cultivation on soil microbiomes in three niches: soil below fungal beds, soil from furrows, and control forest soil with no influence from mushroom cultivation. Nutrients were accumulated in the soil below fungal beds with a significant increase (p < 0.05) in SOC, total C, total N, available P, and the activities of glucosidase and cellobiosidase. Non-metric multidimensional scaling and PERMANOVA results indicated that the structure of the microbiomes had been significantly (p < 0.05) shaped among the different niches. Soil furrows were microbial hotspots characterized by the higher microbial diversity and richness. Moreover, the increased microbiome abundance (assessed through qPCR) and the high number of significant stimulated functional types (based on MetaCyc genome database) indicated an enhanced functional capacity in furrows. Together, these results provide a comprehensive understanding of the microbial assemblies and the differently influenced soil properties in mushroom cultivation areas.

scholarly journals Development of the Equine Hindgut Microbiome in Semi-feral and Domestic Conventionally-Managed Foals

2020 ◽  
Author(s):  
Meredith Tavenner ◽  
Sue M McDonnell ◽  
Amy S Biddle
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Gut Microbiome ◽  
Feral Horses ◽  
Microbiome Diversity ◽  
Domestic Horses ◽  
Species Groups ◽  
The Impact ◽  
Bacterial Groups ◽  
Lactobacillus Spp

Abstract Background Early development of the gut microbiome is an essential part of neonate health in animals. It is unclear whether the acquisition of gut microbes is different between domesticated animals and their wild counterparts. In this study, fecal samples from ten domestic conventionally managed (DCM) Standardbred and ten semi-feral managed (SFM) Shetland-type pony foals and dams were compared using 16S rRNA sequencing to identify differences in the development of the foal hindgut microbiome related to time and management. Results Gut microbiome diversity of dams was higher than foals overall, and foals from both groups at Week 1 had less diverse gut microbiomes than subsequent weeks. The core microbiomes of SFM dams and foals had more taxa overall, and greater numbers of taxa within species groups when compared to DCM dams and foals. The gut microbiomes of SFM foals demonstrated enhanced diversity of key groups: Verrucomicrobia (RFP12), Ruminococcaceae, Fusobacterium spp., and Bacteroides spp., based on age and management. Lactic acid bacteria Lactobacillus spp. and Lactobacillaceae gen. were enriched only in DCM foals, specifically during their second and third week of life. Predicted microbiome functions estimated computationally suggested that SFM foals had higher mean sequence counts for taxa contributing to the digestion of lipids, simple and complex carbohydrates, and protein. DCM foal microbiomes were more similar to their dams in week five and six than were SFM foals at the same age. Conclusions This study demonstrates the impact of management on the development of the foal gut microbiome in the first 6 weeks of life. The higher numbers of taxa within and between bacterial groups found in SFM dams and foals suggests more diversity and functional redundancy in their gut microbiomes, which could lend greater stability and resiliency to these communities. The colonization of lactic acid bacteria in the early life of DCM foals suggests enrichment in response to the availability of dams’ feed. Thus, management type is an important driver of gut microbiome establishment on horses, and we may look to semi-feral horses for guidance in defining a healthy gut microbiome for domestic horses.

scholarly journals Covariation of the Fecal Microbiome with Diet in Nonpasserine Birds

mSphere ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
Kangpeng Xiao ◽  
Yutan Fan ◽  
Zhipeng Zhang ◽  
Xuejuan Shen ◽  
Xiaobing Li ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Dietary Diversity ◽  
Basal Diet ◽  
Metagenomic Sequencing ◽  
Sequencing Data ◽  
Future Health ◽  
Amino Acid Synthesis ◽  
Fecal Samples ◽  
Fecal Microbiome ◽  
Microbiome Diversity

ABSTRACT Opportunistic feeding and multiple other environment factors can modulate the gut microbiome, and bias conclusions, when wild animals are used for studying the influence of phylogeny and diet on their gut microbiomes. Here, we controlled for these other confounding factors in our investigation of the magnitude of the effect of diet on the gut microbiome assemblies of nonpasserine birds. We collected fecal samples, at one point in time, from 35 species of birds in a single zoo as well as 6 species of domestic poultry from farms in Guangzhou city to minimize the influences from interfering factors. Specifically, we describe 16S rRNA amplicon data from 129 fecal samples obtained from 41 species of birds, with additional shotgun metagenomic sequencing data generated from 16 of these individuals. Our data show that diets containing native starch increase the abundance of Lactobacillus in the gut microbiome, while those containing plant-derived fiber mainly enrich the level of Clostridium. Greater numbers of Fusobacteria and Proteobacteria are detected in carnivorous birds, while in birds fed a commercial corn-soybean basal diet, a stronger inner-connected microbial community containing Clostridia and Bacteroidia was enriched. Furthermore, the metagenome functions of the microbes (such as lipid metabolism and amino acid synthesis) were adapted to the different food types to achieve a beneficial state for the host. In conclusion, the covariation of diet and gut microbiome identified in our study demonstrates a modulation of the gut microbiome by dietary diversity and helps us better understand how birds live based on diet-microbiome-host interactions. IMPORTANCE Our study identified food source, rather than host phylogeny, as the main factor modulating the gut microbiome diversity of nonpasserine birds, after minimizing the effects of other complex interfering factors such as weather, season, and geography. Adaptive evolution of microbes to food types formed a dietary-microbiome-host interaction reciprocal state. The covariation of diet and gut microbiome, including the response of microbiota assembly to diet in structure and function, is important for health and nutrition in animals. Our findings help resolve the major modulators of gut microbiome diversity in nonpasserine birds, which had not previously been well studied. The diet-microbe interactions and cooccurrence patterns identified in our study may be of special interest for future health assessment and conservation in birds.

scholarly journals Development of the Equine Hindgut Microbiome in Semi-feral and Domestic Conventionally-Managed Foals

2020 ◽  
Author(s):  
Meredith Tavenner ◽  
Sue M McDonnell ◽  
Amy S Biddle
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Gut Microbiome ◽  
Feral Horses ◽  
Microbiome Diversity ◽  
Rrna Sequencing ◽  
Domestic Horses ◽  
Species Groups ◽  
The Impact ◽  
Bacterial Groups

Abstract Background: Early development of the gut microbiome is an essential part of neonate health in animals. It is unclear whether the acquisition of gut microbes is different between domesticated animals and their wild counterparts. In this study, fecal samples from ten domestic conventionally managed (DCM) Standardbred and ten semi-feral managed (SFM) Shetland-type pony foals and dams were compared using 16S rRNA sequencing to identify differences in the development of the foal hindgut microbiome related to time and management. Results: Gut microbiome diversity of dams was lower than foals overall and within groups, and foals from both groups at Week 1 had less diverse gut microbiomes than subsequent weeks. The core microbiomes of SFM dams and foals had more taxa overall, and greater numbers of taxa within species groups when compared to DCM dams and foals. The gut microbiomes of SFM foals demonstrated enhanced diversity of key groups: Verrucomicrobia (RFP12), Ruminococcaceae, Fusobacterium spp., and Bacteroides spp., based on age and management. Lactic acid bacteria Lactobacillus spp. and other Lactobacillaceae genera were enriched only in DCM foals, specifically during their second and third week of life. Predicted microbiome functions estimated computationally suggested that SFM foals had higher mean sequence counts for taxa contributing to the digestion of lipids, simple and complex carbohydrates, and protein. DCM foal microbiomes were more similar to their dams in week five and six than were SFM foals at the same age.Conclusions: This study demonstrates the impact of management on the development of the foal gut microbiome in the first 6 weeks of life. The higher numbers of taxa within and between bacterial groups found in SFM dams and foals suggests more diversity and functional redundancy in their gut microbiomes, which could lend greater stability and resiliency to these communities. The colonization of lactic acid bacteria in the early life of DCM foals suggests enrichment in response to the availability of dams’ feed. Thus, management type is an important driver of gut microbiome establishment on horses, and we may look to semi-feral horses for guidance in defining a healthy gut microbiome for domestic horses.

Impact of VEGF and CgA as new predictive tools in management of elderly hormone-refractory prostate cancer (HRPC) patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16070-e16070
Author(s):  
I. Carreca ◽  
F. Bellomo ◽  
S. Burgio ◽  
P. D'Alia ◽  
D. Piazza ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Response ◽  
Clinical Benefit ◽  
Tumour Response ◽  
Progression Free Survival ◽  
Somatostatin Analogues ◽  
Biochemical Response ◽  
Somatostatin Analogue ◽  
Hormone Refractory ◽  
Pre Treatment

e16070 Background: Prostate cancer is one of the most frequent malignancy in men of the Western countries. The identification of new predictive factors of drug activity is crucial for elderly cancer patients, who need a particular selection according to prediction of efficacy and safety by pre-treatment parameters. Several prostate cancers show focal neuroendocrine (NE) spots and CgA seems to be associated to NE phenotype both in tissue and in circulation. VEGF expression in NE cells is corelated with clinical characteristics and disease-specific survival. Somatostatin analogues induce a decrease in plasma CgA and could have also anti-angiogenic activity by inhibition of VEGF, bFGF and GH/IGF-I axis. Methods: elderly patients, median age 75 (range: 65–83), were selected for hormone-refractory disease, previously treated with CAB. Serum PSA and plasmatic CgA and VEGF were evaluated in all pts at baseline (T0) and at 4 months (T4) and 8 months (T8) after therapy. Pts were treated with docetaxel 75 mg/m2 every 3 weeks for 6 cycles and octreotide acetate 20 mg administered intramuscularly every 4 weeks until progression. Clinical and biochemical response, progression- free survival and toxicity were also evaluated. A correlation of basal CgA and VEGF with biochemical response, clinical response and clinical benefit was also investigated. Results: Median duration of follow-up was 18 months (range: 8–32). Patients evaluable for response were 22. PSA response rate (RR) was observed in 10/22 (45%); clinical objective RR was 33% (7/22). Clinical benefit was observed in 19/22 pts (86%). Only mild toxicities was observed in both groups. CgA and VEGF were both strongly reduced after therapy. Lower CgA values correlated with clinical benefit, lower VEGF values also correlated with biochemical and clinical response. Conclusions: This combination treatment showed a good toxicity profile. The most relevant data in this study refer to the role of serum CgA and VEGF levels, for prediction of tumour response. If these findings were confirmed, it could be sufficient to measure these markers levels for identification of those HRPC patients who have more probability of obtaining clinical benefit from a docetaxel-based treatment in combination with a somatostatin analogue. No significant financial relationships to disclose.

DKN-01 in combination with pembrolizumab in patients with advanced gastroesophageal adenocarcinoma (GEA): Tumoral DKK1 expression as a predictor of response and survival.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 357-357 ◽  
Author(s):  
Samuel J. Klempner ◽  
Johanna C. Bendell ◽  
Victoria Meucci Villaflor ◽  
Laura LaNiel Tenner ◽  
Stacey Stein ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Benefit ◽  
Objective Response ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Clinical Activity ◽  
Kaplan Meier ◽  
Dkk1 Expression ◽  
Clinical Benefit Response ◽  
Gastroesophageal Adenocarcinoma

357 Background: Dickkopf-1 (DKK1) modulates Wnt signaling and contributes to an immune suppressive tumor microenvironment. DKN-01 (D), a neutralizing DKK1 antibody + pembrolizumab (P) has demonstrated safety and clinical activity in advanced GEA. We report response and survival outcomes in anti-PD-1/anti-PD-L1 naïve GEA patients by high/low tumoral DKK1 expression. Methods: We enrolled advanced anti-PD-1/PD-L1 naïve GEA patients (pts) in a Phase 1b/2a study of D + P (NCT02013154). Tumoral DKK1 mRNA expression was assessed by an in situ hybridization RNAscope assay. Objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS) were compared between DKK1 high and low groups. Kaplan-Meier method and Cox-PH model was used for survival analysis and logistic regression was used for clinical benefit/response outcome. Results: 34 GEA pts were enrolled to receive 300 mg D + P. 31 GEA pts had DKK1 expression available (25 response-evaluable/RE) and 27 had both DKK1 and PD-L1 expression available (22 RE). In RE pts, DKK1 high (H-score ≥ upper-tertile [≥35]) had an ORR of 50% (5 PR/10), DCR of 80% (8/10) while DKK1 low ( < upper-tertile) had an ORR of 0% (0/15) and DCR of 20% (3/15); DKK1 high (vs. low) had an OR of 16 (95%CI: 2.2, 118.3; n = 25) and adjusted (for PD-L1 CPS ≥10 vs. < 10) OR of 17.6 (95%CI:1.6, 194.4; n = 22) for clinical benefit/response (PR/SD vs. PD). Median PFS was 22.1 weeks in DKK1 high (n = 11) vs. 5.9 weeks in DKK1 low (n = 20); HR of 0.23 (95%CI: 0.082, 0.66; n = 31). Adjusted (for PD-L1 expression) HR for DKK1 high was 0.20 (95%CI: 0.061,0.68; n = 27) for PFS. DKK1 high (n = 11) had a median OS of 31.6 weeks vs. 17.4 weeks in DKK1 low (n = 20); HR of 0.45 (95%CI: 0.16, 1.3; n = 31) and adjusted HR of 0.62 (95%CI: 0.2,1.9; n = 27). Conclusions: High levels of tumoral DKK1 expression identify advanced anti-PD-1/PD-L1 naïve GEA pts with the greatest benefit from D + P. Improvements in response/clinical benefit and PFS were observed independent of PD-L1 expression. Tumoral DKK1 as a potential predictive biomarker for DKN-01 treated GEA pts will be evaluated in future studies. Overall survival follow-up is ongoing. Clinical trial information: NCT02013154.

scholarly journals A fructo-oligosaccharide prebiotic is well-tolerated in adults undergoing allogeneic hematopoietic stem cell transplantation: a phase I dose-escalation trial

2021 ◽  
Author(s):  
Tessa. M. Andermann ◽  
Farnaz Fouladi ◽  
Fiona B. Tamburini ◽  
Bita Sahaf ◽  
Ekaterina Tkachenko ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Phase I ◽  
Cell Transplantation ◽  
Gut Microbiome ◽  
Metagenomic Sequencing ◽  
Microbiota Composition ◽  
Hematopoietic Stem ◽  
The Impact ◽  
Gut Microbiota Composition ◽  
Reduced Intensity

AbstractBackgroundAlterations of the gut microbiota after allogeneic hematopoietic cell transplantation (allo-HCT) are a key factor in the development of transplant-related complications such as graft-versus-host disease (GVHD). Interventions that preserve the gut microbiome hold promise to improve HCT-associated morbidity and mortality. Murine models demonstrate that prebiotics such as fructo-oligosaccharides (FOS) may increase gut levels of short-chain fatty acids (SCFAs) such as butyrate, and consequently induce proliferation of immunomodulatory CD4+ FOXP3+ T-regulatory cells (Tregs), that impact GVHD risk.MethodsWe conducted a pilot Phase I trial to assess the investigate the maximum tolerated dose of FOS in patients undergoing reduced-intensity (RIC) allo-HCT (n=15) compared to concurrent controls (n=16). We administered FOS starting at pretransplant conditioning and continuing for a total of 21 days. We characterized the gut microbiome using shotgun metagenomic sequencing, measured stool SCFAs using LC-MS, and determined peripheral T-cell concentrations using CyTOF.ResultsWe found that FOS was safe and well-tolerated at 10g per day without significant adverse effects in patients undergoing reduced-intensity conditioning allo-HCT. Community-level gut microbiota composition was significantly different on the day of transplant (day 0) between patients receiving FOS compared to concurrent controls, however FOS-associated alterations of the gut microbiota were not sustained after transplant. Although the impact of FOS was fleeting, transplantation itself impacted a substantial number of taxa over time. In our small pilot trial, no significant differences were observed in gut microbial metabolic pathways, stool SCFAs, or in peripheral Tregs although Tregs trended higher in those patients who received FOS. Early alterations in gut microbiota composition in those receiving FOS are especially intriguing although it remains unclear what impact this has on outcomes following transplantation and larger studies are required to investigate the use of prebiotics in HCT recipients.ConclusionsFOS is well-tolerated at 10g per day in patients undergoing RIC allo-HCT.

Randomized prospective trial assessing Bifidobacterium-containing probiotic supplementation in metastatic renal cell carcinoma (mRCC) patients receiving vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5078-5078
Author(s):  
Nazli Dizman ◽  
Joann Hsu ◽  
Paulo Gustavo Bergerot ◽  
John D Gillece ◽  
Megan Folkerts ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Kinase Inhibitors ◽  
Randomized Study ◽  
Prospective Trial ◽  
Progression Free Survival ◽  
Metagenomic Sequencing ◽  
Microbiome Composition ◽  
Shotgun Metagenomic Sequencing ◽  
Pre Treatment ◽  
Endothelial Growth Factor

5078 Background: Studies suggest a link between the gut microbiome and mRCC outcomes, including evidence that mRCC patients (pts) possess a lower abundance of Bifidobacterium spp compared to healthy adults (Pal et al Clin Cancer Res 2015). The aim of this study was to assess if Bifidobacterium-containing probiotics could modulate the gut microbiome and impact rates of clinical benefit (CB) from VEGF-TKIs. Methods: Pts initiating VEGF-TKI therapy for mRCC were randomized to probiotic supplemented (PSu) or probiotic restricted (PRe) treatment arms. Pts in the PSu arm consumed two 4 oz servings of Activia daily. Stool samples were collected prior to therapy and at wks 2, 3, 4 and 12. Gut microbiota composition was assessed using whole genome shotgun metagenomic sequencing (Zhu et al Microbiome 2018). The primary endpoint was change in Bifidobacterium spp with therapy. Microbiome composition was compared across pts with CB (complete/partial response or stable disease) versus no CB (NCB). Results: In total, 20 pts were enrolled. The most frequent VEGF-TKIs were cabozantinib (45%), sunitinib (25%) and lenvatinib (25%). Median progression-free survival (PFS) was 6.5 months (95%CI 0.3-12.9) and CB rate was 75%. Bifidobacterium animalis, the active ingredient of Activia, reached detectable levels in all pts in the PSu arm, but was only detectable in one pt in the PRe arm. CB rate was not significantly different in PSu vs PRe arms (70% vs 80%, p > 0.05), and there was no difference in PFS. LDA effect size (LEfSe) analysis of MetaPhIAn2 data captured 25 enriched species demonstrating an LDA score > 3 in either CB or NCB. Of those with high LDA scores, Barnesiella intesitinihominis and Akkermansia municiphila were the most significant members (p = 7.4 x 10−6 and p = 5.6 10−3, respectively). While 92% of B. intestinihominis positive pts obtained a CB, only 50% of B. intestinihominis negative pts obtained CB (p = 0.036). Conclusions: This is the first prospective randomized study demonstrating modulation of the gut microbiome with probiotics in mRCC. While microbiome modulation by probiotics did not increase CB rates as intended, consecutive stool specimens allowed us to identify an association between B. intesitinihominis, A. municiphila and CB with VEGF-TKIs. In addition to the previously documented association between A. municiphila and immunotherapy outcome (Routy et al. Science 2018), this species may predict activity with VEGF-TKIs. Clinical trial information: NCT02944617 .

A WHOLE FOOD, ANTI-INFLAMMATORY DIET ESTABLISHES A BENEFICIAL GUT MICROBIOME IN INFLAMMATORY BOWEL DISEASE PATIENTS

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S38-S38
Author(s):  
Barbara Olednzki ◽  
Vanni Bucci ◽  
Caitlin Cawley ◽  
Ana Maldonado-Contreras
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Response ◽  
Bowel Disease ◽  
Gut Microbiome ◽  
Dietary Intervention ◽  
Bacterial Species ◽  
Model Complex ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
The Impact

Abstract Background and Aims The inflammatory bowel disease-anti-inflammatory diet (IBD-AID) is a whole food diet designed to favor the development of an anti-inflammatory microbiome and to assist with remission in patients suffering from inflammatory bowel disease (IBD). Herein, we evaluated the effect of the IBD-AID on the gut microbiome and defined the impact of specific foods on bacteria depleted in IBD patients, as well as the clinical response to the IBD-AID. Methods A single-arm, pre-post intervention trial was performed. After a baseline period, a dietary intervention was initiated. We collected stool and blood samples throughout the study and assessed dietary intake and disease severity. We applied advanced computational approaches to define and model complex interactions between the diet, microbiota, and response to the IBD-AID. Results A dense dataset comprising 553 dietary records and 340 stool samples was compiled from 22 subjects participating in the study. The IBD-AID favored bacteria that are normally depleted in IBD cohorts and capable of producing short-chain fatty acids (SCFAs). Consumption of non-starchy vegetables, nuts, and seeds positively correlated with increased abundance of SCFA-producing bacteria, including Roseburia hominis, Eubacterium eligens,and Faecalibacterium prausnitzii. Half of the subjects completing the intervention with high diet adherence (&gt;60%) reported a positive clinical response to the IBD-AID, with a subset of bacterial species predicting diet-induced reduction of symptoms with 67% accuracy. After the intervention, subjects also exhibited a reduction of circulating inflammatory markers. Conclusions The IBD-AID favors the growth of SCFA-producing bacteria that are depleted during IBD dysbiosis. The microbiome signatures emerging after the IBD-AID can predict response to the diet.

scholarly journals The Gut Microbiome and Cancer Immunotherapy: Can We Use the Gut Microbiome as a Predictive Biomarker for Clinical Response in Cancer Immunotherapy?

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4824
Author(s):  
Byeongsang Oh ◽  
Frances Boyle ◽  
Nick Pavlakis ◽  
Stephen Clarke ◽  
Thomas Eade ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Clinical Response ◽  
Metastatic Melanoma ◽  
Cancer Immunotherapy ◽  
Gut Microbiome ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Fecal Microbiota Transplant ◽  
Cell Lung Carcinoma ◽  
Fecal Microbiome

Background: Emerging evidence suggests that gut microbiota influences the clinical response to immunotherapy. This review of clinical studies examines the relationship between gut microbiota and immunotherapy outcomes. Method: A literature search was conducted in electronic databases Medline, PubMed and ScienceDirect, with searches for “cancer” and “immunotherapy/immune checkpoint inhibitor” and “microbiome/microbiota” and/or “fecal microbiome transplant FMT”. The relevant literature was selected for this article. Results: Ten studies examined patients diagnosed with advanced metastatic melanoma (n = 6), hepatocellular carcinoma (HCC) (n = 2), non-small cell lung carcinoma (NSCLC) (n = 1) and one study examined combination both NSCLC and renal cell carcinoma (RCC) (n = 1). These studies consistently reported that the gut microbiome profile prior to administering immune checkpoint inhibitors (ICIs) was related to clinical response as measured by progression-free survival (PFS) and overall survival (OS). Two studies reported that a low abundance of Bacteroidetes was associated with colitis. Two studies showed that patients with anti-PD-1 refractory metastatic melanoma experienced improved response rates and no added toxicity when receiving fecal microbiota transplant (FMT) from patients with anti-PD-1 responsive disease. Conclusions: Overall, significant differences in the diversity and composition of the gut microbiome were identified in ICIs responders and non-responders. Our findings provide new insights into the value of assessing the gut microbiome in immunotherapy. Further robust randomized controlled trials (RCTs) examining the modulatory effects of the gut microbiome and FMT on ICIs in patients not responding to immunotherapy are warranted.

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