Capsaicin as a Microbiome Modulator: Metabolic Interactions and Implications for Host Health

<b>Background/Objectives:</b> Capsaicin is the principal pungent compound in chili peppers and is increasingly recognized as a multifunctional phytochemical with systemic effects beyond its sensory properties. It has been linked to metabolic regulation, neuroprotection, inflammation cont...

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Main Authors: Iván Artemio Corral-Guerrero, Angela Elena Martínez-Medina, Litzy Yazmin Alvarado-Mata, Ana Cristina Figueroa Chávez, Roberto Muñoz-García, Miriam Paulina Luévanos-Escareño, Jazel Doménica Sosa-Martínez, María José Castro-Alonso, Padma Nimmakayala, Umesh K. Reddy, Nagamani Balagurusamy
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/15/6/372
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author Iván Artemio Corral-Guerrero
Angela Elena Martínez-Medina
Litzy Yazmin Alvarado-Mata
Ana Cristina Figueroa Chávez
Roberto Muñoz-García
Miriam Paulina Luévanos-Escareño
Jazel Doménica Sosa-Martínez
María José Castro-Alonso
Padma Nimmakayala
Umesh K. Reddy
Nagamani Balagurusamy
author_facet Iván Artemio Corral-Guerrero
Angela Elena Martínez-Medina
Litzy Yazmin Alvarado-Mata
Ana Cristina Figueroa Chávez
Roberto Muñoz-García
Miriam Paulina Luévanos-Escareño
Jazel Doménica Sosa-Martínez
María José Castro-Alonso
Padma Nimmakayala
Umesh K. Reddy
Nagamani Balagurusamy
author_sort Iván Artemio Corral-Guerrero
collection DOAJ
description <b>Background/Objectives:</b> Capsaicin is the principal pungent compound in chili peppers and is increasingly recognized as a multifunctional phytochemical with systemic effects beyond its sensory properties. It has been linked to metabolic regulation, neuroprotection, inflammation control, and cancer modulation. This review aims to provide an integrative synthesis of capsaicin’s metabolism, its interaction with the gut microbiome, and its physiological implications across organ systems. <b>Methods:</b> We conducted a critical literature review of recent in vivo and in vitro studies exploring capsaicin’s metabolic fate, biotransformation by host enzymes and gut microbes, tissue distribution, and molecular pathways. The literature was analyzed thematically to cover gastrointestinal absorption, hepatic metabolism, microbiota interactions, and systemic cellular responses. <b>Results:</b> Capsaicin undergoes extensive hepatic metabolism, producing hydroxylated and dehydrogenated metabolites that differ in transient receptor potential vanilloid type 1 (TRPV1) receptor affinity and tissue-specific bioactivity. It crosses the blood–brain barrier, alters neurotransmitter levels, and accumulates in brain regions involved in cognition. In addition to its systemic effects, capsaicin appears to undergo microbial transformation and influences gut microbial composition, favoring short-chain fatty acid producers and suppressing pro-inflammatory taxa. These changes contribute to anti-obesity, anti-inflammatory, and potentially anticancer effects. Dose-dependent adverse outcomes, such as epithelial damage or tumor promotion, have also been observed. <b>Conclusions:</b> Capsaicin represents a diet-derived bioactive molecule whose systemic impact is shaped by dynamic interactions between host metabolism and the gut microbiota. Clarifying its biotransformation pathways and context-specific effects is essential for its safe and effective use in metabolic and neurological health strategies.
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spelling doaj-art-eab565ded57548089f8e0699655e71f32025-08-20T03:27:15ZengMDPI AGMetabolites2218-19892025-06-0115637210.3390/metabo15060372Capsaicin as a Microbiome Modulator: Metabolic Interactions and Implications for Host HealthIván Artemio Corral-Guerrero0Angela Elena Martínez-Medina1Litzy Yazmin Alvarado-Mata2Ana Cristina Figueroa Chávez3Roberto Muñoz-García4Miriam Paulina Luévanos-Escareño5Jazel Doménica Sosa-Martínez6María José Castro-Alonso7Padma Nimmakayala8Umesh K. Reddy9Nagamani Balagurusamy10Laboratorio de Biorremediación, Facultad de Ciencias Biológicas, Universidad Autónoma de Coahuila, Torreón 27000, MexicoLaboratorio de Biorremediación, Facultad de Ciencias Biológicas, Universidad Autónoma de Coahuila, Torreón 27000, MexicoLaboratorio de Biorremediación, Facultad de Ciencias Biológicas, Universidad Autónoma de Coahuila, Torreón 27000, MexicoLaboratorio de Biorremediación, Facultad de Ciencias Biológicas, Universidad Autónoma de Coahuila, Torreón 27000, MexicoLaboratorio de Biorremediación, Facultad de Ciencias Biológicas, Universidad Autónoma de Coahuila, Torreón 27000, MexicoLaboratorio de Biorremediación, Facultad de Ciencias Biológicas, Universidad Autónoma de Coahuila, Torreón 27000, MexicoLaboratorio de Biorremediación, Facultad de Ciencias Biológicas, Universidad Autónoma de Coahuila, Torreón 27000, MexicoLaboratorio de Biorremediación, Facultad de Ciencias Biológicas, Universidad Autónoma de Coahuila, Torreón 27000, MexicoDepartment of Biology, Gus R. Douglass Institute, West Virginia State University, Institute, Dunbar, WV 25112-1000, USADepartment of Biology, Gus R. Douglass Institute, West Virginia State University, Institute, Dunbar, WV 25112-1000, USALaboratorio de Biorremediación, Facultad de Ciencias Biológicas, Universidad Autónoma de Coahuila, Torreón 27000, Mexico<b>Background/Objectives:</b> Capsaicin is the principal pungent compound in chili peppers and is increasingly recognized as a multifunctional phytochemical with systemic effects beyond its sensory properties. It has been linked to metabolic regulation, neuroprotection, inflammation control, and cancer modulation. This review aims to provide an integrative synthesis of capsaicin’s metabolism, its interaction with the gut microbiome, and its physiological implications across organ systems. <b>Methods:</b> We conducted a critical literature review of recent in vivo and in vitro studies exploring capsaicin’s metabolic fate, biotransformation by host enzymes and gut microbes, tissue distribution, and molecular pathways. The literature was analyzed thematically to cover gastrointestinal absorption, hepatic metabolism, microbiota interactions, and systemic cellular responses. <b>Results:</b> Capsaicin undergoes extensive hepatic metabolism, producing hydroxylated and dehydrogenated metabolites that differ in transient receptor potential vanilloid type 1 (TRPV1) receptor affinity and tissue-specific bioactivity. It crosses the blood–brain barrier, alters neurotransmitter levels, and accumulates in brain regions involved in cognition. In addition to its systemic effects, capsaicin appears to undergo microbial transformation and influences gut microbial composition, favoring short-chain fatty acid producers and suppressing pro-inflammatory taxa. These changes contribute to anti-obesity, anti-inflammatory, and potentially anticancer effects. Dose-dependent adverse outcomes, such as epithelial damage or tumor promotion, have also been observed. <b>Conclusions:</b> Capsaicin represents a diet-derived bioactive molecule whose systemic impact is shaped by dynamic interactions between host metabolism and the gut microbiota. Clarifying its biotransformation pathways and context-specific effects is essential for its safe and effective use in metabolic and neurological health strategies.https://www.mdpi.com/2218-1989/15/6/372capsaicinmicrobiotahost–microbiome interactionsnutritional modulation
spellingShingle Iván Artemio Corral-Guerrero
Angela Elena Martínez-Medina
Litzy Yazmin Alvarado-Mata
Ana Cristina Figueroa Chávez
Roberto Muñoz-García
Miriam Paulina Luévanos-Escareño
Jazel Doménica Sosa-Martínez
María José Castro-Alonso
Padma Nimmakayala
Umesh K. Reddy
Nagamani Balagurusamy
Capsaicin as a Microbiome Modulator: Metabolic Interactions and Implications for Host Health
Metabolites
capsaicin
microbiota
host–microbiome interactions
nutritional modulation
title Capsaicin as a Microbiome Modulator: Metabolic Interactions and Implications for Host Health
title_full Capsaicin as a Microbiome Modulator: Metabolic Interactions and Implications for Host Health
title_fullStr Capsaicin as a Microbiome Modulator: Metabolic Interactions and Implications for Host Health
title_full_unstemmed Capsaicin as a Microbiome Modulator: Metabolic Interactions and Implications for Host Health
title_short Capsaicin as a Microbiome Modulator: Metabolic Interactions and Implications for Host Health
title_sort capsaicin as a microbiome modulator metabolic interactions and implications for host health
topic capsaicin
microbiota
host–microbiome interactions
nutritional modulation
url https://www.mdpi.com/2218-1989/15/6/372
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