Monday, December 22, 2025 12/22/2025

Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV

Award Number: R01DA050542
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2025

Group Awards By:

View Award Description

Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV - Abstract/Project Summary Chronic opioid use is associated with gut microbial dysbiosis, gut barrier disruption and systemic bacterial translocation. Gut leakiness, microbial translocation and systemic inflammation are hallmarks of HIV disease progression. In recent years, much attention has been focused towards elucidating the impact of Toll-like receptors (TLRs) in microglial activation and NLRP3 inflammasome assembly as a mechanism for sustained neuroinflammation and neurocognitive disease progression. While previous studies have investigated the direct effect of HIV associated toxic proteins (TAT and gp120) and opioids on inflammasome activation on microglial little is known about the role of gut derived products and their impact on inflammasome activation and neurocognitive disorders that are prevalent in substance using HIV patients. Although most studies correlate endotoxin levels and bacterial products derived from gram-negative bacteria with inflammation and HIV disease progression, recent studies clearly show a distinct enrichment and prevalence of gram positive bacterial communities in HIV infected patients when compared to normal healthy individuals. Our central hypothesis is that microbial dysbiosis with predominant expansion of Gram positive bacterial communities leading to systemic leakage of G+ bacterial products serve as cognate ligands on TLR2 on microglial cells leading to TLR2 activation and induction of inflammasome components assembly. Our central hypothesis is supported by the following preliminary data. Using a rodent model of HIV in the context of drug abuse, we demonstrate 1) Significant increase in a) gut bacterial translocation b) systemic inflammation c) NLRP3 expression on microglial cells in HIV infected animals that are dramatically exacerbated in HIV+ Morphine treated animals when compared to their respective controls. 2) Morphine induced NLRP3 expression is only observed in the presence of TLR2 cognate ligand in BV2 microglial cells. We will test the hypothesis that gut- microbiota immune brain axis activate inflammasome signaling pathways in brain microglial cells leading to sustained inflammation contributing to the neuropathology of HAND in an opioid abusing HIV infected patients. Aim 1: We will establish the role of the gut microbiota in microglial inflammasome activation using a) germ free mice b) differential antibiotic (gram specific depletion)treated mice and c) infection with gram positive Enterococcus Faecalis. We will also investigate if sex of the animals serves as a biological variable in microglia NLRP3 activation in our model of opioid dependence in the context of HIV infection. Aim 2: Determine the role of TLR2 in NLRP3 induction in microglial cells using tissue specific deletion by breeding floxed TLR2 with microglial specific cre expression using Cx3Cr1 Cre mice. Aim 3: Determine if combination of probiotics and TLR2 antagonist attenuate NLRP3 induction on microglial cells.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$48,282 )
2026	2023	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Drug Use and Addiction Research Programs	000	5	12/10/2025	NON-COMPETING CONTINUATION	-$48,282
														Subtotal = -$48,282

Issue Date FY: 2023 ( Subtotal = $422,934 )
2023	2023	UNIVERSITY OF MIAMI	1400 NW 10TH AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Drug Use and Addiction Research Programs	001	5	6/9/2023	SUPPLEMENT FOR EXPANSION	$44,265
2023	2023	UNIVERSITY OF MIAMI	1400 NW 10TH AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Drug Use and Addiction Research Programs	000	5	6/8/2023	NON-COMPETING CONTINUATION	$378,669
														Subtotal = $422,934

Issue Date FY: 2022 ( Subtotal = $576,434 )
2022	2022	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Drug Use and Addiction Research Programs	001	4	6/27/2022	NON-COMPETING CONTINUATION	$378,669
2022	2022	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Drug Use and Addiction Research Programs	002	4	6/28/2022	SUPPLEMENT FOR EXPANSION	$44,265
2022	2022	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Drug Use and Addiction Research Programs	003	4	6/29/2022	SUPPLEMENT FOR EXPANSION	$153,500
2022	2021	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Drug Use and Addiction Research Programs	000	3	5/2/2022	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $576,434

Issue Date FY: 2021 ( Subtotal = $616,777 )
2021	2021	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Drug Use and Addiction Research Programs	002	3	6/23/2021	SUPPLEMENT FOR EXPANSION	$153,500
2021	2021	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Drug Use and Addiction Research Programs	001	3	6/22/2021	SUPPLEMENT FOR EXPANSION	$84,608
2021	2021	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Drug Use and Addiction Research Programs	000	3	6/18/2021	NON-COMPETING CONTINUATION	$378,669
														Subtotal = $616,777

Issue Date FY: 2020 ( Subtotal = $464,287 )
2020	2020	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Drug Use and Addiction Research Programs	001	2	7/2/2020	SUPPLEMENT FOR EXPANSION	$84,608
2020	2020	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Drug Use and Addiction Research Programs	000	2	6/17/2020	NON-COMPETING CONTINUATION	$379,679
														Subtotal = $464,287

Issue Date FY: 2019 ( Subtotal = $377,433 )
2019	2019	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Drug Use and Addiction Research Programs	000	1	9/17/2019	NEW	$377,433
														Subtotal = $377,433

Grand Total All Awards = $2,409,583

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV

Award Number: R01DA050542

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/30/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer