Abstract LB109: Network analysis of gut microbiome throughout a whole foods based high fiber dietary intervention reveals complex community dynamics in melanoma survivors
Authors: Mousavi Daniel Cyrus , Mishra Aditya , Jiang Yan , Kus Tessa M. , Levy Erma , Montalvo Marco , Ajami Nadim , Wargo Jennifer , MacDougall Carrie , McQuade Jennifer McQuade 
Published: April 2023

Abstract
Recent evidence has demonstrated that the gut microbiome modulates response to immune checkpoint blockade (ICB) treatment in melanoma patients. Microbiome modulation via a habitual high-fiber diet was associated with significantly improved progression-free survival (PFS) in melanoma patients on ICB. Previous findings have suggested that this pro-response is associated with known fiber-responsive taxa and Short Chain Fatty Acid (SCFA) producing taxa. However, little is known about the communications responsible for stimulating the aforementioned taxa. To explore community dynamics and identify potential keystone communicating taxa, we conducted microbial association network analysis throughout a high-fiber dietary intervention (HFDI) in melanoma survivors. Ten patients were enrolled to the HFDI study and were provided with whole-food-based fiber-enriched meals for the duration of six weeks. Fecal samples were collected longitudinally, and whole genome sequencing (WGS) of the fecal microbiome was used to calculate microbiome composition profiles. OTU abundance data was then used to construct, analyze, and compare association networks across timepoints via the R package NetCoMi. Overall changes in community dynamics were assessed via changes in global network properties, and significant taxa were identified quantitatively via differences in calculated centrality measures as well as visually by NetCoMi’s selection of hubs, or specific keystone taxa. Network analysis across timepoints demonstrated a general increase in connectivity by both quantitative and visual comparison throughout the HFDI. Analysis via multiple association statistics revealed a general rise in several measures of centrality of many known fiber- responsive and SCFA-producing taxa, with many consistently becoming hub taxa. Consensus networks generated by overlapping several networks generated from different association statistics revealed a consistent increase in centrality in two particular species: Ruminococcus bromii and Dorea longicatena. Analysis of networks constructed from only differentially associated taxa revealed similar results, with R. bromii and D. longicatena having numerous changes in associations with fiber-responsive taxa. Increases in general connectivity measures indicate that a HFDI prompts the gut microbiome to become a more interconnected and dynamic community over time. This, in conjunction with an overall increase in centrality in known fiber-responsive and SCFA-producing taxa, reflects an overall pro-response to the HFDI. Networks constructed via different association statistics yield varied results, with many identifying different taxa as hubs. Despite this heterogeneity, network analysis consistently identified D. longicatena and R. bromii as potential keystone species with an important role in communicating with fiber-responsive taxa. Further analyses are needed to characterize communications between keystone species and SCFA-producing taxa.
Citation Format: Daniel Cyrus Mousavi, Aditya Mishra, Yan Jiang, Tessa M. Kus, Erma Levy, Marco Montalvo, Nadim Ajami, Jennifer Wargo, Carrie MacDougall, Jennifer McQuade McQuade. Network analysis of gut microbiome throughout a whole foods based high fiber dietary intervention reveals complex community dynamics in melanoma survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB109.