Our Research

Exploring The Diverse World of the Gut Microbiome In Shaping Human Health

The Biome Lab at UTHealth is dedicated to investigating the signaling mechanisms underlying gut-brain axis interactions in aging-associated cerebrovascular diseases and related neurological conditions, including stroke, Alzheimer's disease, cerebral amyloid angiopathy, gestational diabetes, and neonatal hypoxic encephalopathy. Each experiment brings us one step closer to understanding the complex and dynamic world of the gut microbiome.

Bacterial Amyloid Curli Associated Gut Epithelial Neuroendocrine Activation Predominantly Observed in Alzheimer's Disease Mice with Central Amyloid-β Pathology

In this study, we investigated how gut bacteria may contribute to Alzheimer's disease. We focused on curli, a bacterial amyloid protein, and found that its presence in the gut activated immune and nerve signaling pathways, including TLR2 expression, changes in gut bacteria, and elevated neuroendocrine markers. Our findings suggest that bacterial amyloid in the gut can influence gut-brain communication and may play a role in driving the brain pathology seen in Alzheimer's disease.

Interlink Between the Gut Microbiota and Inflammation in the Context of Oxidative Stress in Alzheimer's Disease Progression

This review discusses how gut microbiota influences Alzheimer's disease through the microbiota-gut-brain axis, particularly via inflammation, oxidative stress, and metabolic pathways. It highlights how gut dysbiosis may accelerate disease progression by promoting neuroinflammation, toxin production, and amyloid-β accumulation. The review also examines current strategies to restore gut balance, such as reducing pro-inflammatory signals and enhancing beneficial microbial metabolites. Overall, targeting the gut microbiome is presented as a promising avenue for future diagnosis and treatment.

Stabilizing Histamine Release in Gut Mast Cells Mitigates Peripheral and Central Inflammation After Stroke

We investigated how mast cells and histamine drive inflammation after stroke using an aged mouse model. We found that stabilizing mast cells with cromolyn reduced histamine levels, limited immune cell trafficking to the brain, improved gut barrier function, and enhanced recovery. These findings identify the gut-brain immune axis as an important contributor to stroke outcomes and a promising target for therapy.

Benefits of Equilibrium Between Microbiota-and Host-Derived Ligands of the Aryl Hydrocarbon Receptor After Stroke in Aged Male Mice

This study shows that after a stroke, disruptions in the gut microbiome reduce beneficial microbiota-derived molecules that normally regulate brain inflammation. At the same time, an increase in host-derived molecules creates an imbalance that affects the aryl hydrocarbon receptor (AHR) pathway. This work highlights that these changes influence microglial activity, which plays a key role in post-stroke neuroinflammation. Restoring a balanced pool of host- and microbiota-derived AHR ligands may be a beneficial therapeutic strategy after stroke.

Common Signaling Pathways Involved in Alzheimer's Disease and Stroke: Two Faces of the Same Coin

In this review, we explore the shared molecular mechanisms underlying Alzheimer's disease (AD) and ischemic stroke (IS) to understand their etiological connections better. We summarize key signaling cascades common to both conditions, including autotoxicity, ApoE4, insulin signaling, inflammation, mTOR-autophagy, Notch signaling, and the microbiota-gut-brain axis. These pathways provide a clearer understanding of disease pathology and may serve as a foundation for developing more effective, targeted therapeutics.

Other Publications

Monga S, Flores S, Blasco-Conesa MP, Rahman SM, Noh B, Peesh P, Ganesh BP, Marrelli SP, McCullough LD, Moruno-Manchon JF. E2f1 Overexpression Reduces Aging-Associated DNA Damage in Cultured Cerebral Endothelial Cells and Improves Cognitive Performance in Aged Mice. Oxid Med Cell Longev. 2025;2025:3242282. doi: 10.1155/omcl/3242282. eCollection 2025. PubMed PMID: 40761766; PubMed Central PMCID: PMC12321429.

Kothari R, Abdulrahim MW, Oh HJ, Capuzzi DH, Kilgore CB, Nair SK, Zhang Y, Limjunyawong N, Saini SS, Kim JE, Caplan JM, Gonzalez FL, Jackson CM, Bettegowda C, Huang J, Ganesh BP, Tan C, Koehler RC, Tamargo RJ, McCullough LD, Xu R, Dong X. A mast cell receptor mediates post-stroke brain inflammation via a dural-brain axis. Cell. 2025 Oct 2;188(20):5499-5515.e20. doi: 10.1016/j.cell.2025.06.045. Epub 2025 Jul 24. PubMed PMID: 40712576; PubMed Central PMCID: PMC12313293.

Escarcega RD, M J VK, Kyriakopoulos VE, Ortiz GJ, Gusdon AM, Fan H, Peesh P, Blasco Conesa MP, Colpo GD, Ahnstedt HW, Couture L, Kim SH, Hinojosa M, Farrell CM, Marrelli SP, Urayama A, Ganesh BP, Schulz PE, McCullough LD, Tsvetkov AS. Serum metabolome profiling in patients with mild cognitive impairment reveals sex differences in lipid metabolism. Neurobiol Dis. 2025 Jan;204:106747. doi: 10.1016/j.nbd.2024.106747. Epub 2024 Nov 29. PubMed PMID: 39617329.

Hudobenko J, Di Gesù CM, Mooz PR, Petrosino J, Putluri N, Ganesh BP, Rebeles K, Blixt FW, Venna VR, McCullough LD. Maternal dysbiosis produces long-lasting behavioral changes in offspring. Mol Psychiatry. 2025 May;30(5):1847-1858. doi: 10.1038/s41380-024-02794-0. Epub 2024 Oct 23. PubMed PMID: 39443733; PubMed Central PMCID: PMC12014497.

Svačina MKR, Gao T, Sprenger-Svačina A, Lin J, Ganesh BP, Lee J, McCullough LD, Sheikh KA, Zhang G. Rejuvenating fecal microbiota transplant enhances peripheral nerve repair in aged mice by modulating endoneurial inflammation. Exp Neurol. 2024 Jun;376:114774. doi: 10.1016/j.expneurol.2024.114774. Epub 2024 Apr 9. PubMed PMID: 38599367.

Noh B, Blasco-Conesa MP, Rahman SM, et al. Iron overload induces cerebral endothelial senescence in aged mice and in primary culture in a sex-dependent manner. Aging Cell. 2023 Nov;22(11):e13977. DOI: 10.1111/acel.13977. PMID: 37675802; PMCID: PMC10652299.

Lee J, Peesh P, Quaicoe V, Tan C, Banerjee A, Mooz P, Ganesh BP, Petrosino J, Bryan RM Jr, McCullough LD, Venna VR. Estradiol mediates colonic epithelial protection in aged mice after stroke and is associated with shifts in the gut microbiome. Gut Microbes. 2023 Dec;15(2):2271629. doi: 10.1080/19490976.2023.2271629. Epub 2023 Nov 1. PubMed PMID: 37910478; PubMed Central PMCID: PMC10730206.

Conesa MPB, Blixt FW, Peesh P, Khan R, Korf J, Lee J, Jagadeesan G, Andersohn A, Das TK, Tan C, Di Gesu C, Colpo GD, Moruno-Manchón JF, McCullough LD, Bryan R, Ganesh BP. Stabilizing histamine release in gut mast cells mitigates peripheral and central inflammation after stroke. J Neuroinflammation. 2023 Oct 7;20(1):230. doi: 10.1186/s12974-023-02887-7. PubMed PMID: 37805585; PubMed Central PMCID: PMC10560441.

Ganesh BP, Peesh P, Blasco MP, Hamamy AE, Khan R, Guzman G, Honarpisheh P, Mohan EC, Goodman GW, Nguyen JN, Banerjee A, Ko KA, Korf J, Tan C, Fan H, Colpo G, Ahnstedt H, Couture L, Kofler J, Moruno-Manchon J, Maniskas M, Aronowski J, Lee J, Li J, Bryan RM, Chauhan A, Venna VR, McCullough L. Restoring a balanced pool of host-derived and microbiota-derived ligands of the aryl hydrocarbon receptor is beneficial after stroke. Res Sq. 2023 Sep 13;. doi: 10.21203/rs.3.rs-3143015/v1. PubMed PMID: 37790313; PubMed Central PMCID: PMC10543021.

Noh B, Blasco-Conesa MP, Rahman SM, Monga S, Ritzel R, Guzman G, Lai YJ, Ganesh BP, Urayama A, McCullough LD, Moruno-Manchon JF. Iron overload induces cerebral endothelial senescence in aged mice and in primary culture in a sex-dependent manner. Aging Cell. 2023 Nov;22(11):e13977. doi: 10.1111/acel.13977. Epub 2023 Sep 7. PubMed PMID: 37675802; PubMed Central PMCID: PMC10652299.

Giridharan VV, Catumbela CSG, Catalão CHR, Lee J, Ganesh BP, Petronilho F, Dal-Pizzol F, Morales R, Barichello T. Sepsis exacerbates Alzheimer's disease pathophysiology, modulates the gut microbiome, increases neuroinflammation and amyloid burden. Mol Psychiatry. 2023 Oct;28(10):4463-4473. doi: 10.1038/s41380-023-02172-2. Epub 2023 Jul 14. PubMed PMID: 37452088; PubMed Central PMCID: PMC10926876.

Ngwa C, Al Mamun A, Qi S, Sharmeen R, Conesa MPB, Ganesh BP, Manwani B, Liu F. Central IRF4/5 Signaling Are Critical for Microglial Activation and Impact on Stroke Outcomes. Transl Stroke Res. 2024 Aug;15(4):831-843. doi: 10.1007/s12975-023-01172-2. Epub 2023 Jul 11. PubMed PMID: 37432594; PubMed Central PMCID: PMC10782817.

Korf JM, Honarpisheh P, Mohan EC, Banerjee A, Blasco-Conesa MP, Honarpisheh P, Guzman GU, Khan R, Ganesh BP, Hazen AL, Lee J, Kumar A, McCullough LD, Chauhan A. CD11b(high) B Cells Increase after Stroke and Regulate Microglia. J Immunol. 2022 Jul 15;209(2):288-300. doi: 10.4049/jimmunol.2100884. Epub 2022 Jun 22. PubMed PMID: 35732342; PubMed Central PMCID: PMC9446461.

Escarcega RD, Honarpisheh P, Colpo GD, Ahnstedt HW, Couture L, Juneja S, Torres G, Ortiz GJ, Sollome J, Tabor N, Ganesh BP, Choi HA, Liu F, McCullough LD, Tsvetkov AS. Sex differences in global metabolomic profiles of COVID-19 patients. Cell Death Dis. 2022 May 14;13(5):461. doi: 10.1038/s41419-022-04861-2. PubMed PMID: 35568706; PubMed Central PMCID: PMC9106988.

Korf JM, Ganesh BP, McCullough LD. Gut dysbiosis and age-related neurological diseases in females. Neurobiol Dis. 2022 Jun 15;168:105695. doi: 10.1016/j.nbd.2022.105695. Epub 2022 Mar 18. Review. PubMed PMID: 35307514; PubMed Central PMCID: PMC9631958.

Noh B, Blasco-Conesa MP, Lai YJ, Ganesh BP, Urayama A, Moreno-Gonzalez I, Marrelli SP, McCullough LD, Moruno-Manchon JF. G-quadruplexes Stabilization Upregulates CCN1 and Accelerates Aging in Cultured Cerebral Endothelial Cells. Front Aging. 2021;2:797562. doi: 10.3389/fragi.2021.797562. eCollection 2021. PubMed PMID: 35822045; PubMed Central PMCID: PMC9261356.

Nelson JW, Phillips SC, Ganesh BP, Petrosino JF, Durgan DJ, Bryan RM. The gut microbiome contributes to blood-brain barrier disruption in spontaneously hypertensive stroke prone rats. FASEB J. 2021 Feb;35(2):e21201. doi: 10.1096/fj.202001117R. PubMed PMID: 33496989; PubMed Central PMCID: PMC8238036.

Patrizz A, Dono A, Zorofchian S, Hines G, Takayasu T, Husein N, Otani Y, Arevalo O, Choi HA, Savarraj J, Tandon N, Ganesh BP, Kaur B, McCullough LD, Ballester LY, Esquenazi Y. Glioma and temozolomide induced alterations in gut microbiome. Sci Rep. 2020 Dec 3;10(1):21002. doi: 10.1038/s41598-020-77919-w. PubMed PMID: 33273497; PubMed Central PMCID: PMC7713059.

Honarpisheh P, Lee J, Banerjee A, Blasco-Conesa MP, Honarpisheh P, d'Aigle J, Mamun AA, Ritzel RM, Chauhan A, Ganesh BP, McCullough LD. Potential caveats of putative microglia-specific markers for assessment of age-related cerebrovascular neuroinflammation. J Neuroinflammation. 2020 Dec 1;17(1):366. doi: 10.1186/s12974-020-02019-5. PubMed PMID: 33261619; PubMed Central PMCID: PMC7709276.

Honarpisheh P, Blixt FW, Blasco Conesa MP, Won W, d'Aigle J, Munshi Y, Hudobenko J, Furr JW, Mobley A, Lee J, Brannick KE, Zhu L, Hazen AL, Bryan RM, McCullough LD, Ganesh BP. Peripherally-sourced myeloid antigen presenting cells increase with advanced aging. Brain Behav Immun. 2020 Nov;90:235-247. doi: 10.1016/j.bbi.2020.08.023. Epub 2020 Aug 27. PubMed PMID: 32861719; PubMed Central PMCID: PMC8169202.

Dono A, Patrizz A, McCormack RM, Putluri N, Ganesh BP, Kaur B, McCullough LD, Ballester LY, Esquenazi Y. Glioma induced alterations in fecal short-chain fatty acids and neurotransmitters. CNS Oncol. 2020 Jun;9(2):CNS57. doi: 10.2217/cns-2020-0007. Epub 2020 Jun 30. PubMed PMID: 32602743; PubMed Central PMCID: PMC7341178.

Blasco MP, Chauhan A, Honarpisheh P, Ahnstedt H, d'Aigle J, Ganesan A, Ayyaswamy S, Blixt F, Venable S, Major A, Durgan D, Haag A, Kofler J, Bryan R, McCullough LD, Ganesh BP. Age-dependent involvement of gut mast cells and histamine in post-stroke inflammation. J Neuroinflammation. 2020 May 19;17(1):160. doi: 10.1186/s12974-020-01833-1. PubMed PMID: 32429999; PubMed Central PMCID: PMC7236952.

Luck B, Engevik MA, Ganesh BP, Lackey EP, Lin T, Balderas M, Major A, Runge J, Luna RA, Sillitoe RV, Versalovic J. Bifidobacteria shape host neural circuits during postnatal development by promoting synapse formation and microglial function. Sci Rep. 2020 May 8;10(1):7737. doi: 10.1038/s41598-020-64173-3. PubMed PMID: 32385412; PubMed Central PMCID: PMC7210968.

Hudobenko J, Ganesh BP, Jiang J, Mohan EC, Lee S, Sheth S, Morales D, Zhu L, Kofler JK, Pautler RG, McCullough LD, Chauhan A. Growth differentiation factor-11 supplementation improves survival and promotes recovery after ischemic stroke in aged mice. Aging (Albany NY). 2020 May 4;12(9):8049-8066. doi: 10.18632/aging.103122. Epub 2020 May 4. PubMed PMID: 32365331; PubMed Central PMCID: PMC7244081.

Lee J, d'Aigle J, Atadja L, Quaicoe V, Honarpisheh P, Ganesh BP, Hassan A, Graf J, Petrosino J, Putluri N, Zhu L, Durgan DJ, Bryan RM Jr, McCullough LD, Venna VR. Gut Microbiota-Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice. Circ Res. 2020 Jul 31;127(4):453-465. doi: 10.1161/CIRCRESAHA.119.316448. Epub 2020 May 1. PubMed PMID: 32354259; PubMed Central PMCID: PMC7415518.

Honarpisheh P, Reynolds CR, Blasco Conesa MP, Moruno Manchon JF, Putluri N, Bhattacharjee MB, Urayama A, McCullough LD, Ganesh BP. Dysregulated Gut Homeostasis Observed Prior to the Accumulation of the Brain Amyloid-β in Tg2576 Mice. Int J Mol Sci. 2020 Mar 3;21(5). doi: 10.3390/ijms21051711. PubMed PMID: 32138161; PubMed Central PMCID: PMC7084806.

Fultz R, Engevik MA, Shi Z, Hall A, Herrmann B, Ganesh BP, Major A, Haag A, Mori-Akiyama Y, Versalovic J. Phagocytosis by macrophages depends on histamine H2 receptor signaling and scavenger receptor 1. Microbiologyopen. 2019 Oct;8(10):e908. doi: 10.1002/mbo3.908. Epub 2019 Aug 1. PubMed PMID: 31369218; PubMed Central PMCID: PMC6813435.

Ritzel RM, Al Mamun A, Crapser J, Verma R, Patel AR, Knight BE, Harris N, Mancini N, Roy-O'Reilly M, Ganesh BP, Liu F, McCullough LD. CD200-CD200R1 inhibitory signaling prevents spontaneous bacterial infection and promotes resolution of neuroinflammation and recovery after stroke. J Neuroinflammation. 2019 Feb 18;16(1):40. doi: 10.1186/s12974-019-1426-3. PubMed PMID: 30777093; PubMed Central PMCID: PMC6378746.

Versalovic J, Highlander SK, Ganesh BP, Petrosino JF. The Human Microbiome. American Society of Microbiology. Book Chapter.. 2018.

Labib E, Blaut M, Hussein L, Gouda M, Lynette Kramer D, Ganesh BP, Schumann P, Woting A, Fouad MT. Molecular Diversity of Gut Microbiota and Short Chain Fatty Acids in Egyptian Adults Following Dietary Intervention with Fermented Sobya. J Food Microbiol Saf Hyg. 2018; 3(2).

Ganesh BP, Nelson JW, Eskew JR, Ganesan A, Ajami NJ, Petrosino JF, Bryan RM Jr, Durgan DJ. Prebiotics, Probiotics, and Acetate Supplementation Prevent Hypertension in a Model of Obstructive Sleep Apnea. Hypertension. 2018 Nov;72(5):1141-1150. doi: 10.1161/HYPERTENSIONAHA.118.11695. PubMed PMID: 30354816; PubMed Central PMCID: PMC6209125.

Spychala MS, Venna VR, Jandzinski M, Doran SJ, Durgan DJ, Ganesh BP, Ajami NJ, Putluri N, Graf J, Bryan RM, McCullough LD. Age-related changes in the gut microbiota influence systemic inflammation and stroke outcome. Ann Neurol. 2018 Jul;84(1):23-36. doi: 10.1002/ana.25250. Epub 2018 Jul 18. PubMed PMID: 29733457; PubMed Central PMCID: PMC6119509.

Chauhan A, Hudobenko J, Al Mamun A, Koellhoffer EC, Patrizz A, Ritzel RM, Ganesh BP, McCullough LD. Myeloid-specific TAK1 deletion results in reduced brain monocyte infiltration and improved outcomes after stroke. J Neuroinflammation. 2018 May 17;15(1):148. doi: 10.1186/s12974-018-1188-3. PubMed PMID: 29776451; PubMed Central PMCID: PMC5960093.

Ganesh BP, Fultz R, Ayyaswamy S, Versalovic J. Microbial interactions with the intestinal epithelium and beyond: Focusing on immune cell maturation and homeostasis. Curr Pathobiol Rep. 2018 Mar;6(1):47-54. doi: 10.1007/s40139-018-0165-y. Epub 2018 Mar 5. PubMed PMID: 30294506; PubMed Central PMCID: PMC6171525.

Gao C, Ganesh BP, Shi Z, Shah RR, Fultz R, Major A, Venable S, Lugo M, Hoch K, Chen X, Haag A, Wang TC, Versalovic J. Gut Microbe-Mediated Suppression of Inflammation-Associated Colon Carcinogenesis by Luminal Histamine Production. Am J Pathol. 2017 Oct;187(10):2323-2336. doi: 10.1016/j.ajpath.2017.06.011. Epub 2017 Sep 13. PubMed PMID: 28917668; PubMed Central PMCID: PMC5809336.

Ganesh BP, Hall A, Ayyaswamy S, Nelson JW, Fultz R, Major A, Haag A, Esparza M, Lugo M, Venable S, Whary M, Fox JG, Versalovic J. Diacylglycerol kinase synthesized by commensal Lactobacillus reuteri diminishes protein kinase C phosphorylation and histamine-mediated signaling in the mammalian intestinal epithelium. Mucosal Immunol. 2018 Mar;11(2):380-393. doi: 10.1038/mi.2017.58. Epub 2017 Jul 26. PubMed PMID: 28745328; PubMed Central PMCID: PMC5785580.

Durgan DJ, Ganesh BP, Cope JL, Ajami NJ, Phillips SC, Petrosino JF, Hollister EB, Bryan RM Jr. Role of the Gut Microbiome in Obstructive Sleep Apnea-Induced Hypertension. Hypertension. 2016 Feb;67(2):469-74. doi: 10.1161/HYPERTENSIONAHA.115.06672. Epub 2015 Dec 28. PubMed PMID: 26711739; PubMed Central PMCID: PMC4713369.

Ganesh BP, Versalovic J. Luminal Conversion and Immunoregulation by Probiotics. Front Pharmacol. 2015;6:269. doi: 10.3389/fphar.2015.00269. eCollection 2015. Review. PubMed PMID: 26617521; PubMed Central PMCID: PMC4641912.

Ganesh BP, Klopfleisch R, Loh G, Blaut M. Commensal Akkermansia muciniphila exacerbates gut inflammation in Salmonella Typhimurium-infected gnotobiotic mice. PLoS One. 2013;8(9):e74963. doi: 10.1371/journal.pone.0074963. eCollection 2013. PubMed PMID: 24040367; PubMed Central PMCID: PMC3769299.

Ganesh BP, Richter JF, Blaut M, Loh G. Enterococcus faecium NCIMB 10415 does not protect interleukin-10 knock-out mice from chronic gut inflammation. Benef Microbes. 2012 Mar 1;3(1):43-50. doi: 10.3920/BM2011.0050. PubMed PMID: 22348908.

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