Reduced Gut Microbiome Diversity in People With HIV Who Have Distal Neuropathic Pain

Gut dysbiosis, defined as pathogenic alterations in the distribution and abundance of dif-ferent microbial species, is associated with neuropathic pain in a variety of clinical conditions, but this has not been explored in the context of neuropathy in people with HIV (PWH). We assessed gut microbial diversity and dysbiosis in PWH and people without HIV (PWoH), some of whom reported distal neuropathic pain (DNP). DNP was graded on a standardized, validated severity scale. The gut microbiome was characterized using 16S rRNA sequencing and diversity was assessed using phyloge-netic tree construction. Songbird analysis (https://github.com/mortonjt/songbird) was used to pro-duce a multinomial regression model predicting counts of specific microbial taxa through metadata covariate columns. Participants were 226 PWH and 101 PWoH, mean (SD) age 52.0 (13.5), 21.1% female, 54.7% men who have sex with men, 44.7% non-white. Among PWH, median (interquartile range, IQR) nadir and current CD4 were 174 (21, 302) and 618 (448, 822), respectively; 90% were virally suppressed on antiretroviral therapy. PWH and PWoH did not differ with respect to microbiome diver-sity as indexed by Faith's phylogenetic diversity (PD). More severe DNP was associated with lower alpha diversity as indexed by Faith's phylogenetic diversity in PWH (Spearman's r = .224, P = 0.0007), but not in PWoH (Spearman's r = .032, P = .748). These relationships were not confounded by demo-graphics or disease factors. In addition, the log-ratio of features identified at the genus level as Blau-tia to Lachnospira was statistically significantly higher in PWH with DNP than in PWH without DNP (t -test, P = 1.01e-3). Furthermore, the log-ratio of Clostridium features to Lachnospira features also was higher in PWH with DNP than in those without (t-test, P = 6.24e-5). Our results, in combination with previous findings in other neuropathic pain conditions, suggest that gut dysbiosis, particularly reduc-tions in diversity and relative increases in the ratios of Blautia and Clostridium to Lachnospira, may contribute to prevalent DNP in PWH. Two candidate pathways for these associations, involving micro-bial pro-inflammatory components and microbially-produced anti-inflammatory short chain fatty acids, are discussed. Future studies might test interventions to re-establish a healthy gut microbiota and determine if this prevents or improves DNP. Perspective: The association of neuropathic pain in people with HIV with reduced gut microbial diversity and dysbiosis raises the possibility that re-establishing a healthy gut microbiota might ame-liorate neuropathic pain in HIV by reducing proinflammatory and increasing anti-inflammatory micro-bial products. (c) 2021 The Author(s). Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Automated summary

The analysis of gut microbial diversity and dysbiosis in PWH and PWoH revealed that more severe DNP was associated with lower alpha diversity in PWH. Specific changes in microbial taxa ratios were also observed in PWH with DNP. These findings suggest that gut dysbiosis may contribute to prevalent DNP in PWH.