Fig. 6

Longitudinal changes in microbiome with development and resolution of toxicities. (a) Analysis identified five patients who had submitted multiple samples during development and resolution of irAE. JZLC-24 and JZLC-6 did not have stool samples available for analysis but did submit all three sets of nasal and buccal samples. On the x-axis, sample collections are listed: V1, prior to initiation of immunotherapy; V2; at onset of toxicity, and V3, at resolution of irAE. The y-axis denotes the logarithmic (base 10) relative change in α -diversity compared to the previous visit, trended by the line plots, overlaid. Across nearly all sets of microbiome samples, a drop in microbiome α-diversity is observed at onset of irAE. At resolution of irAE to grade 1 severity or better, a third set of samples exhibit a trend toward either slowed rate of decrease in α-diversity or a reversal altogether toward baseline. (b) A consistent trend in increase of Staphylococcus at onset of toxicity and decrease with resolution of toxicity was also observed in the nasal samples (left), with a similar trend in buccal samples (right). (c) Megasphaera, a bacterium belonging to Firmicutes, was previously identified as being enriched in responders to immunotherapy. Here, it is also shown to decrease in buccal samples of patients who developed irAEs, then increasing in abundance with resolution of toxicity