1
|
Petersen C, Satheesh Babu AK, Della Lucia CM, Paz HA, Iglesias-Carres L, Zhong Y, Jalili T, Symons JD, Shankar K, Neilson AP, Wankhade UD, Anandh Babu PV. Gut microbes metabolize strawberry phytochemicals and mediate their beneficial effects on vascular inflammation. Gut Microbes 2025; 17:2446375. [PMID: 39760464 DOI: 10.1080/19490976.2024.2446375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 11/02/2024] [Accepted: 12/18/2024] [Indexed: 01/07/2025] Open
Abstract
Evidence suggests that a healthy gut microbiome is essential for metabolizing dietary phytochemicals. However, the microbiome's role in metabolite production and the influence of gut dysbiosis on this process remain unclear. Further, studies on the relationship among gut microbes, metabolites, and biological activities of phytochemicals are limited. We addressed this knowledge gap using strawberry phytochemicals as a model. C57BL/6J mice were fed a standard diet [C]; strawberry-supplemented diet (~2 human servings) [CS]; strawberry-supplemented diet and treated with antibiotics (to deplete gut microbes) [CSA]; high-fat diet (HFD) [HF]; strawberry-supplemented HFD [HS]; and strawberry-supplemented HFD and treated with antibiotics [HSA] for 12 weeks. First, antibiotic treatment suppressed the production of selected metabolites (CSA vs. CS), and p-coumaric acid was identified as a strawberry-derived microbial metabolite. Second, HFD-induced dysbiosis negatively affected metabolite production (HS vs. HF), and hippuric acid was identified as a microbial metabolite in HFD conditions. Third, dietary strawberries improved HFD-induced vascular inflammation (HS vs. HF). However, antibiotic treatment reduced metabolite production and abolished the vascular effects of strawberries (HSA vs. HS), indicating the importance of gut microbes in mediating the vascular benefits of strawberries via metabolites. Fourth, strawberry supplementation decreased Coprobacillus that was positively associated with vascular inflammation, whereas it increased Lachnospiraceae that was negatively associated with vascular inflammation and positively associated with hippuric acid. Fifth, hippuric acid was negatively associated with vascular inflammation. Our study fills in some pieces of the giant puzzle regarding the influence of gut microbes on the biological activities of phytochemicals. HFD-induced gut dysbiosis negatively impacts metabolite production and a strong association exists among gut microbes, strawberry-derived microbial metabolites, and the vascular benefits of dietary strawberries. Further, our study provides significant proof of concept to warrant future research on the use of strawberries as a nutritional strategy to prevent vascular complications.
Collapse
Affiliation(s)
- Chrissa Petersen
- Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, UT, USA
| | | | - Ceres Mattos Della Lucia
- Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, UT, USA
| | - Henry A Paz
- Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Lisard Iglesias-Carres
- Plants for Human Health Institute, Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Kannapolis, NC, USA
| | - Ying Zhong
- Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Thunder Jalili
- Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, UT, USA
| | - J David Symons
- Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, UT, USA
| | - Kartik Shankar
- Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Andrew P Neilson
- Plants for Human Health Institute, Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Kannapolis, NC, USA
| | - Umesh D Wankhade
- Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Pon Velayutham Anandh Babu
- Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, UT, USA
| |
Collapse
|
2
|
Kim D, Kim S, Choi G, Lee G, Song J, Oh YT, Youn JH, Cho S. The polyphenol/caffeine ratio determines the arousal-inducing properties of the green tea ethanol extract. Food Funct 2025; 16:3694-3706. [PMID: 40245063 DOI: 10.1039/d5fo00661a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/19/2025]
Abstract
Green tea (Camellia sinensis L.), one of the most popular beverages worldwide, contains caffeine, a natural stimulant. However, some green tea extracts have been known to possess both hypnotic and arousal effects. This study aimed to identify the components influencing these dual effects using a green tea ethanol extract (GE). Response surface methodology revealed that only some extraction conditions significantly induced arousal effects in ICR mice during the pentobarbital-induced sleep test. Among these, extraction with 95% ethanol for 195 minutes achieved the maximum arousal effect, corresponding to a caffeine content of 58.9 mg g-1, comparable to the effects observed with the reference, 25 mg kg-1 of caffeine. In addition, administration of this GE sample significantly increased wakefulness for 3 hours following treatment in C57BL/6N mice, as confirmed through sleep architecture analysis. A correlation analysis of the total phenolic content (TPC) to caffeine ratio in GE found that the intensity of the arousal-inducing effects varied with TPC (R2 = 0.9428). It was also confirmed that the ratio of EGCG to caffeine, major components of GE, was more closely associated with sleep duration (R2 = 0.9034). L-Theanine, known for its sleep-promoting effects, did not independently affect the arousal effects of GE. However, when combined with EGCG, their total content showed a slightly stronger correlation with sleep duration in relation to the caffeine ratio, compared with that of EGCG/caffeine ratio (R2 = 0.9464). Therefore, the balance between TPC and caffeine appears to modulate the stimulant properties of GE, highlighting its potential as both a stimulant and a mild hypnotic agent. Collectively, these findings provide insights into optimizing GE for tailored functional foods based on its polyphenol/caffeine ratio.
Collapse
Affiliation(s)
- Duhyeon Kim
- Department of Food Science and Technology/Institute of Food Science, Pukyong National University, Busan 48513, Republic of Korea.
| | - Seonghui Kim
- Department of Food Science and Technology/Institute of Food Science, Pukyong National University, Busan 48513, Republic of Korea.
| | - Gibeom Choi
- Department of Food Science and Technology/Institute of Food Science, Pukyong National University, Busan 48513, Republic of Korea.
| | - Gahyeon Lee
- Department of Food Science and Technology/Institute of Food Science, Pukyong National University, Busan 48513, Republic of Korea.
| | - Junho Song
- Life Science Research Institute, NOVAREX Co., Ltd, 80, Osongsaengmyeong 14 ro, Heungdeok-gu, Cheongju-si 28220, Republic of Korea.
| | - Young Taek Oh
- Department of Physiology and Neuroscience, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
| | - Jang H Youn
- Department of Physiology and Neuroscience, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
| | - Suengmok Cho
- Department of Food Science and Technology/Institute of Food Science, Pukyong National University, Busan 48513, Republic of Korea.
| |
Collapse
|
3
|
Aranda-Carrillo SG, Del Carmen Ramos-Sustaita L, Cárdenas-Castro AP, Gutiérrez-Sarmiento W, Sánchez-Burgos JA, Ruíz-Valdiviezo VM, Sáyago-Ayerdi SG. Microbiota modulation and microbial metabolites produced during the in vitro colonic fermentation of Psidium guajava species. Food Res Int 2025; 208:116228. [PMID: 40263797 DOI: 10.1016/j.foodres.2025.116228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 02/27/2025] [Accepted: 03/11/2025] [Indexed: 04/24/2025]
Abstract
The interaction between gut microbiota and its metabolites is a growing area of research. Therefore, this study analyzed the bioactive compound profile of the indigestible fraction (IF) from Psidium species and evaluated its effects on microbiota composition during in vitro colonic fermentation. Hydroxycinnamic acids, hydroxybenzoic acids, and ellagitannins were the predominant phenolic compounds, with P. friedrichsthalianum ('Cas') exhibiting the highest concentrations. During in vitro colonic fermentation, a reduction in bacterial genera such as Enterobacteriaceae and Klebsiella was observed, while Faecalibacterium, Oscillibacter, Dialister, and Ruminococcaceae positively correlated with phenolic microbial metabolites. These findings suggest that the IF of Psidium species modulates gut microbiota composition and potentially contributes to the production of beneficial metabolites during human colonic fermentation, reinforcing the role of whole fruit consumption as a comprehensive matrix of nutrients and bioactive compounds beneficial to gut health.
Collapse
Affiliation(s)
- Suecia Grissol Aranda-Carrillo
- Tecnológico Nacional de México/ Instituto Tecnológico de Tepic, Av. Tecnológico No 2595, Col. Lagos del Country, CP 63175 Tepic, Nayarit, Mexico
| | - Lourdes Del Carmen Ramos-Sustaita
- Tecnológico Nacional de México/Instituto Tecnológico de Tuxtla-Gutiérrez, Departamento de Ingeniería Química y Bioquímica, Laboratory of Molecular Biology, Carretera Panamericana km 1080, CP 29050 Tuxtla Gutiérrez, Chiapas, Mexico
| | - Alicia Paulina Cárdenas-Castro
- Tecnológico Nacional de México/ Instituto Tecnológico de Tepic, Av. Tecnológico No 2595, Col. Lagos del Country, CP 63175 Tepic, Nayarit, Mexico
| | - Wilbert Gutiérrez-Sarmiento
- Chiapas Medicinal Plant Research Center, Pharmacobiology Experimental Laboratory, Autonomus University of Chiapas, Tuxtla Gutierrez, Chiapas, Mexico
| | - Jorge Alberto Sánchez-Burgos
- Tecnológico Nacional de México/ Instituto Tecnológico de Tepic, Av. Tecnológico No 2595, Col. Lagos del Country, CP 63175 Tepic, Nayarit, Mexico
| | - Víctor Manuel Ruíz-Valdiviezo
- Tecnológico Nacional de México/Instituto Tecnológico de Tuxtla-Gutiérrez, Departamento de Ingeniería Química y Bioquímica, Laboratory of Molecular Biology, Carretera Panamericana km 1080, CP 29050 Tuxtla Gutiérrez, Chiapas, Mexico
| | - Sonia Guadalupe Sáyago-Ayerdi
- Tecnológico Nacional de México/ Instituto Tecnológico de Tepic, Av. Tecnológico No 2595, Col. Lagos del Country, CP 63175 Tepic, Nayarit, Mexico.
| |
Collapse
|
4
|
García-Beltrán A, Lozano Melero A, Martínez Martínez R, Porres Foulquie JM, López Jurado Romero de la Cruz M, Kapravelou G. A Systematic Review of the Beneficial Effects of Berry Extracts on Non-Alcoholic Fatty Liver Disease in Animal Models. Nutr Rev 2025; 83:819-841. [PMID: 39365946 PMCID: PMC11986334 DOI: 10.1093/nutrit/nuae132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/06/2024] Open
Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries and is strongly associated with several metabolic disorders. Plant-derived bioactive extracts, such as berry extracts, with high antioxidant capacity have been used for the treatment and prevention of this pathology. Moreover, they promote circular economy and sustainability. OBJECTIVE To study the beneficial effects of extracts from different parts of berry plants in animal models of NAFLD. DATA SOURCES A systematic research of the MEDLINE (via PubMed), Cochrane, and Scopus databases was conducted to identify relevant studies published after January 2011. In vivo animal studies of NAFLD were included in which berry extracts of different parts of the plant were administered and significantly improved altered biomarkers related to the pathology, such as lipid metabolism and hepatic steatosis, glucose and glycogen metabolism, and antioxidant and anti-inflammatory biomarkers. DATA EXTRACTION Of a total of 203 articles identified, 31 studies were included after implementation of the inclusion and exclusion criteria. DATA ANALYSIS Most of the studies showed a decrease in steatosis and a stimulation of genes related to β-oxidation and downregulation of lipogenic genes, with administration of berry extracts. Berry extracts also attenuated inflammation and oxidative stress. CONCLUSIONS Administration of berry extracts seems to have promising potential in the design of enriched foodstuffs or nutraceuticals for the treatment of NAFLD.
Collapse
Affiliation(s)
- Alejandro García-Beltrán
- Department of Physiology, Biomedical Research Center, Instituto mixto de Deporte y Salud, University of Granada, 18007 Granada, Spain
| | - Aida Lozano Melero
- Department of Physiology, Biomedical Research Center, Instituto mixto de Deporte y Salud, University of Granada, 18007 Granada, Spain
| | - Rosario Martínez Martínez
- Department of Physiology, Biomedical Research Center, Instituto mixto de Deporte y Salud, University of Granada, 18007 Granada, Spain
| | | | | | - Garyfallia Kapravelou
- Department of Physiology, Faculty of Health Sciences, Campus of Melilla, University of Granada, 52005 Granada, Spain
| |
Collapse
|
5
|
Yuan H, Huang H, Du Y, Zhao J, Yu S, Lin Y, Chen Y, Shan C, Zhao Y, Belwal T, Fu X. Sea buckthorn polyphenols on gastrointestinal health and the interactions with gut microbiota. Food Chem 2025; 469:142591. [PMID: 39721439 DOI: 10.1016/j.foodchem.2024.142591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 11/27/2024] [Accepted: 12/19/2024] [Indexed: 12/28/2024]
Abstract
The potential health benefits of sea buckthorn polyphenols (SBP) have been extensively studied, attracting increasing attention from researchers. This paper reviews the composition of SBP, the effects of processing on SBP, its interactions with nutrients, and its protective role in the gastrointestinal tract. Polyphenols influence nutrient absorption and metabolism by regulating the intestinal flora, thereby enhancing bioavailability, protecting the gastrointestinal tract, and altering nutrient structures. Additionally, polyphenols exhibit anti-inflammatory and immunomodulatory effects, promoting intestinal health. The interaction between polyphenols and intestinal flora plays a significant role in gastrointestinal health, supporting the composition and diversity of the gut microbiota. However, further research is needed to emphasize the importance of human trials and to explore the intricate relationship between SBP and gut microbiota, as these insights are crucial for understanding the mechanisms underlying SBP's benefits for the gastrointestinal tract (GIT).
Collapse
Affiliation(s)
- Hexi Yuan
- Key Laboratory of Characteristics Agricultural Product Processing and Quality Control (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China; Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China; Engineering Research Center of Storage and Processing of Xinjiang Characteristic Fruits and Vegetables, Ministry of Education, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China
| | - Hao Huang
- College of Ecology, Lishui University, Lishui 323000, China
| | - Yinglin Du
- Key Laboratory of Characteristics Agricultural Product Processing and Quality Control (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China; Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China; Engineering Research Center of Storage and Processing of Xinjiang Characteristic Fruits and Vegetables, Ministry of Education, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China.
| | - Jiaqi Zhao
- Key Laboratory of Characteristics Agricultural Product Processing and Quality Control (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China; Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China; Engineering Research Center of Storage and Processing of Xinjiang Characteristic Fruits and Vegetables, Ministry of Education, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China
| | - Shiyang Yu
- Key Laboratory of Characteristics Agricultural Product Processing and Quality Control (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China; Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China; Engineering Research Center of Storage and Processing of Xinjiang Characteristic Fruits and Vegetables, Ministry of Education, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China
| | - Yanhong Lin
- Key Laboratory of Characteristics Agricultural Product Processing and Quality Control (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China; Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China; Engineering Research Center of Storage and Processing of Xinjiang Characteristic Fruits and Vegetables, Ministry of Education, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China
| | - Yan Chen
- GOBI Memory Brand Management Co. Ltd, Ninth Division 170 Regiment Sea buckthorn Picking-garden, Tacheng 834700, China
| | - Chunhui Shan
- Key Laboratory of Characteristics Agricultural Product Processing and Quality Control (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China; Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China; Engineering Research Center of Storage and Processing of Xinjiang Characteristic Fruits and Vegetables, Ministry of Education, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China
| | - Yue Zhao
- Key Laboratory of Characteristics Agricultural Product Processing and Quality Control (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China; Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China; Engineering Research Center of Storage and Processing of Xinjiang Characteristic Fruits and Vegetables, Ministry of Education, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China
| | | | - Xizhe Fu
- Key Laboratory of Characteristics Agricultural Product Processing and Quality Control (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China; Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China; Engineering Research Center of Storage and Processing of Xinjiang Characteristic Fruits and Vegetables, Ministry of Education, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang, 832000, China.
| |
Collapse
|
6
|
Porter Starr KN, Connelly MA, Wallis J, North R, Zhang Q, Song K, González-Delgado JM, Brochu HN, Icenhour CR, Iyer LK, Miller MG, Huffman KM, Kraus WE, Bales CW. Effects of Blueberry Consumption on Fecal Microbiome Composition and Circulating Metabolites, Lipids, and Lipoproteins in a Randomized Controlled Trial of Older Adults with Overweight or Obesity: The BEACTIVE Trial. Nutrients 2025; 17:1200. [PMID: 40218958 PMCID: PMC11990464 DOI: 10.3390/nu17071200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 03/21/2025] [Accepted: 03/24/2025] [Indexed: 04/14/2025] Open
Abstract
Background/Objectives: Generous consumption of phytonutrient-rich foods, including blueberries, provides benefits to multiple physiologic and metabolic systems. This study explored the potential that regular, generous blueberry intake could favorably modulate fecal microbiome composition in sedentary older (>60 years) men and women with overweight or obesity (BMI ≥ 25 to 32 kg/m2). Methods: Participants (n = 55) were randomized to daily consumption of either lyophilized blueberry powder (equivalent to 1.5 cups of blueberries) or an indistinguishable placebo powder; both groups participated in weekly supervised exercise classes. Fecal samples were collected at 0 and 12 weeks and frozen. Following this, 16S rRNA gene sequencing was used to profile each participant's fecal microbiome. Blood biomarkers of cardiometabolic health were measured via nuclear magnetic resonance spectroscopy (NMR) pre- and post-treatment. Results: Comparing the baseline and endpoint results for the blueberry (n = 15) and placebo (n = 19) groups, there were no significant overall compositional differences or differences in the level of diversity in the fecal microbiome. However, in subjects whose diet included blueberry powder, there was a significant enrichment (p = 0.049) in the relative abundance of Coriobacteriales incertae sedis, a taxonomic group of bacteria that facilitates the metabolism of dietary polyphenols. The placebo group exhibited significant reductions in total cholesterol, LDL-C, non-HDL-C, total LDL-P, large LDL-P, and ApoB, while the blueberry group exhibited significant reductions in total HDL-P and ApoA-I after 12 weeks compared to baseline. Conclusions: Generous blueberry consumption may upregulate the ability of the older human gut to utilize dietary polyphenols by altering the fecal microbiome. Longer, larger-scale studies with blueberries or blueberry powder are needed to observe improvements in cardiometabolic risk factors in older adults with overweight or obesity.
Collapse
Affiliation(s)
- Kathryn N. Porter Starr
- Center for the Study of Aging and Human Development, Duke University School of Medicine, Durham, NC 27710, USA; (J.W.); (R.N.); (M.G.M.)
- Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; (K.M.H.); (W.E.K.); (C.W.B.)
- Geriatric Research, Education, and Clinical Center, Durham VA Medical Center, Durham, NC 27710, USA
| | | | - Jessica Wallis
- Center for the Study of Aging and Human Development, Duke University School of Medicine, Durham, NC 27710, USA; (J.W.); (R.N.); (M.G.M.)
| | - Rebecca North
- Center for the Study of Aging and Human Development, Duke University School of Medicine, Durham, NC 27710, USA; (J.W.); (R.N.); (M.G.M.)
| | - Qimin Zhang
- Labcorp, Westborough, MA 01581, USA; (Q.Z.); (K.S.); (H.N.B.); (L.K.I.)
| | - Kuncheng Song
- Labcorp, Westborough, MA 01581, USA; (Q.Z.); (K.S.); (H.N.B.); (L.K.I.)
| | | | - Hayden N. Brochu
- Labcorp, Westborough, MA 01581, USA; (Q.Z.); (K.S.); (H.N.B.); (L.K.I.)
| | | | | | - Marshall G. Miller
- Center for the Study of Aging and Human Development, Duke University School of Medicine, Durham, NC 27710, USA; (J.W.); (R.N.); (M.G.M.)
| | - Kim M. Huffman
- Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; (K.M.H.); (W.E.K.); (C.W.B.)
- Department of Medicine, Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC 27710, USA
| | - William E. Kraus
- Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; (K.M.H.); (W.E.K.); (C.W.B.)
- Department of Medicine, Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC 27710, USA
| | - Connie W. Bales
- Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; (K.M.H.); (W.E.K.); (C.W.B.)
- Geriatric Research, Education, and Clinical Center, Durham VA Medical Center, Durham, NC 27710, USA
| |
Collapse
|
7
|
Brasil JMA, Melo NCDO, Sampaio KB, da Costa PCT, Duman H, Karav S, Lima MDS, de Souza EL, Alves JLDB. Impact of a Limosilactobacillus fermentum, Quercetin, and Resveratrol Nutraceutical on Fecal Microbiota Composition and Metabolic Activity in Healthy and Hypertensive Subjects. Foods 2025; 14:986. [PMID: 40231971 PMCID: PMC11941034 DOI: 10.3390/foods14060986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Revised: 03/06/2025] [Accepted: 03/11/2025] [Indexed: 04/16/2025] Open
Abstract
A promising strategy to improve the gut microbiome in hypertension is to target the gut microbiota. This study evaluated the effects of a potential nutraceutical product composed of three strains of Limosilactobacillus (L.) fermentum, quercetin, and resveratrol on the intestinal microbiome of healthy and hypertensive subjects. The nutraceutical product consisting of strains of L. fermentum 139, 263 and 296, fructooligosaccharides (200 mg), quercetin (160 mg), and resveratrol (150 mg) (LfQR) was added to the in vitro fecal fermentation process occurring for 48 h. Fecal samples of healthy and hypertensive subjects were allocated into four groups: (i) healthy controls (CTL); (ii) healthy controls with the addition of LfQR (CTL + LfQR); (iii) hypertensive (HTN) subjects; and (iv) hypertensive subjects with the addition of LfQR (HTN + LfQR). The diversity and composition of the fecal microbiota and the production of microbial metabolites were evaluated. CTL and HTN groups exhibited a distinct gut microbiota composition, as shown by the β-diversity assessment. The addition of the potentially nutraceutical-modulated β-diversity was similar between CTL and HTN groups, suggesting a similar gut microbiome composition after nutraceutical addition. The addition of the nutraceutical product increased the relative abundance of Enterobacteriaceae in the CTL group and that of Lachnospiraceae in the HTN group. The nutraceutical media showed higher levels of sugars (maltose, fructose, and glucose), lactic acid, ethanol, succinic acid, and acetic acid compared to the CTL and HTN media. Although the results are heterogeneous between healthy and hypertensive fermentation media, it was demonstrated that the nutraceutical formulation can modulate the intestinal microbiota and its metabolic activity.
Collapse
Affiliation(s)
- Jéssica Maria Alves Brasil
- Department of Nutrition, Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil; (J.M.A.B.); (N.C.d.O.M.); (K.B.S.); (P.C.T.d.C.); (E.L.d.S.)
| | - Nathalia Caroline de Oliveira Melo
- Department of Nutrition, Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil; (J.M.A.B.); (N.C.d.O.M.); (K.B.S.); (P.C.T.d.C.); (E.L.d.S.)
| | - Karoliny Brito Sampaio
- Department of Nutrition, Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil; (J.M.A.B.); (N.C.d.O.M.); (K.B.S.); (P.C.T.d.C.); (E.L.d.S.)
| | - Paulo César Trindade da Costa
- Department of Nutrition, Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil; (J.M.A.B.); (N.C.d.O.M.); (K.B.S.); (P.C.T.d.C.); (E.L.d.S.)
| | - Hatice Duman
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Çanakkale 17000, Türkiye; (H.D.); (S.K.)
| | - Sercan Karav
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Çanakkale 17000, Türkiye; (H.D.); (S.K.)
| | - Marcos dos Santos Lima
- Department of Technology, Federal Institute of Sertão de Pernambuco, Petrolina 56300-000, PE, Brazil;
| | - Evandro Leite de Souza
- Department of Nutrition, Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil; (J.M.A.B.); (N.C.d.O.M.); (K.B.S.); (P.C.T.d.C.); (E.L.d.S.)
| | - José Luiz de Brito Alves
- Department of Nutrition, Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil; (J.M.A.B.); (N.C.d.O.M.); (K.B.S.); (P.C.T.d.C.); (E.L.d.S.)
| |
Collapse
|
8
|
He L, Yang G, Li T, Li W, Yang R. Metabolic profile of procyanidin A2 by human intestinal microbiota and their antioxidant and hypolipidemic potential in HepG2 cells. Eur J Nutr 2025; 64:113. [PMID: 40056191 DOI: 10.1007/s00394-025-03638-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 02/25/2025] [Indexed: 03/10/2025]
Abstract
PURPOSE Procyanidins have strong potential for antioxidation and decreasing hepatic fat accumulation thus preventing non-alcoholic fatty liver disease (NAFLD). Procyanidin A2 (PCA2), predominately found in cranberries, avocado, peanut red skins and litchi fruit pericarp, is poorly absorbed in the gastrointestinal tract. However, literatures about its metabolic profile by gut microbiota and effects on lipid metabolism are limited. Therefore, the metabolites of PCA2 by human intestinal microbiota as well as their antioxidant and hypolipidemic potential were investigated. METHODS PCA2 was incubated with human intestinal microbiota and the metabolites produced were characterized by UPLC-Q-TOF-MS. The antioxidant and hypolipidemic potential of PCA2 and its microbial metabolites (MPCA2) were evaluated and compared. RESULTS The metabolism of PCA2 resulted in the formation of 14 metabolites, and the highest antioxidant capacity values were reached after 6 h incubation. In addition, PCA2 and MPCA2 were effective in reducing oxidative stress and lipid accumulation induced by oleic acid (OA) in HepG2 cells. They significantly promoted the phosphorylation of AMP-activated protein kinase (AMPK) and thus stimulated hepatic lipolysis by up-regulating of the expression of carnitine palmitoyl transferase I (CPT-I) and suppressed hepatic lipogenesis by down-regulation of the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA) reductase, fatty acid synthase (FAS) and sterol regulatory element binding proteins 1c (SREBP-1c). CONCLUSION Our results indicated that PCA2 and MPCA2 were effective to prevent OA-induced lipid accumulation and oxidative stress in HepG2 cells, implying that microbial metabolites may play a crucial role in the realization of human health effects of PCA2.
Collapse
Affiliation(s)
- Liangqian He
- Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou, 510642, China
| | - Guangmei Yang
- School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China
| | - Tongyun Li
- Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou, 510642, China
| | - Wu Li
- School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China.
| | - Ruili Yang
- Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou, 510642, China.
| |
Collapse
|
9
|
Zhang S, Niu H, Zhu J. Personalized nutrition studies of human gut microbiome-polyphenol interactions utilizing continuous multistaged in vitro fermentation models-a narrative review. Nutr Res 2025; 135:101-127. [PMID: 39999639 DOI: 10.1016/j.nutres.2025.01.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 01/26/2025] [Accepted: 01/27/2025] [Indexed: 02/27/2025]
Abstract
The gut microbiota, a complex community of microorganisms primarily inhabiting the human large intestine, plays a crucial role in human health. Gut dysbiosis, characterized by an imbalance in gut bacterial populations, has been increasingly recognized as a significant factor in the pathogenesis of metabolic diseases such as type 2 diabetes, inflammatory bowel disease, and colorectal cancer. Polyphenols are critical modulators of gut microbial composition and metabolism. However, the extent of polyphenol-induced modulation of the gut microbiome remains largely unexplored. In vitro models offer a convenient and ethical alternative to in vivo studies for investigating nutrient-gut microbiome interactions, facilitating easy sampling and controlled experimental conditions. Among these, continuous multistaged in vitro fermentation models, which simulate different sections of the human gastrointestinal tract (e.g., proximal colon, transverse colon, and distal colon), provide a more accurate representation of the human gut environment compared to single-batch fermentation. Various configurations of these multistaged models have been developed and widely employed in studies examining the effects of polyphenols on the gut microbiome. This review aims to summarize the different configurations of multistaged in vitro fermentation models and recent advancements in their development, highlight key aspects of experimental design, outline commonly used analytical workflows with complementary analyses, and review the restorative effects of polyphenol interventions on dysregulated gut microbiota.
Collapse
Affiliation(s)
- Shiqi Zhang
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
| | - Hanmeng Niu
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
| | - Jiangjiang Zhu
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
| |
Collapse
|
10
|
Carbone K, Sytar O, Sharopov F, Pezzani R, Romano R, Santini A, Kieliszek M, Khan T, Khan K, Caunii A, Habtemariam S, Sharifi-Rad J, Butnariu M. Anticancer Attributes and Multifaceted Pharmacological Implications of Laetrile and Amygdalin. Cell Biol Int 2025; 49:205-220. [PMID: 39873182 DOI: 10.1002/cbin.12276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Revised: 01/07/2025] [Accepted: 01/09/2025] [Indexed: 01/30/2025]
Abstract
Laetrile, known as vitamin B17, is often used interchangeably with amygdalin. Laetrile is a semi-synthesis product of amygdalin, whereas amygdalin is a naturally occurring substance in many plants. Both compounds have a nitrile functional group that, when activated by the intestinal enzyme β-glucosidases, releases hydrogen cyanide. The two compounds have been considered for a long time as alternative therapy for cancer treatment however, findings available in the literature are discordant on the real efficacy of laetrile/amygdalin for the treatment of cancer, often highlighting a negative benefit-risk ratio. In this regard, the study aimed to comprehensively analyze the scientific data on laetrile/amygdalin, with a special emphasis on their pharmacokinetics, underlying pharmacological properties, mode of action as a potent antitumor agent, and effect on human health. The results showed that there is no clear evidence on the efficacy of cancer therapy following laetrile/amygdalin administration, especially at the clinical trial level. However, the in vitro studies of the biological activity of these compounds showed positive effects related to their antifibrotic, anti-inflammatory, antiasthmatic, and immunoregulatory processes. Laetrile's mechanism of action closely resembles amygdalin, affecting cancer signaling pathways. However, due to its cyanide toxicity, it was banned by the food and drug administration (FDA) due to safety concerns. Despite not receiving permission from the FDA, laetrile emerged as an alternative therapy in the 1970s. Nonetheless, continuing research is investigating safer methods of activating Laetrile for targeted cancer treatment. This opens interesting prospects in using these compounds in alternative medical therapies, for which, however, further research is needed.
Collapse
Affiliation(s)
- Katya Carbone
- CREA-Research Centre for Olive, Fruit and Citrus Crops, Rome, Italy
| | - Oksana Sytar
- Department of Plant Biology Department, Taras Shevchenko National University of Kyiv, Institute of Biology, Kyiv, Ukraine
- Department of Plant Physiology, Slovak University of Agriculture, Nitra, Slovakia
| | - Farukh Sharopov
- Research Institution "Chinese-Tajik Innovation Center for Natural Products", National Academy of Sciences of the Republic of Tajikistan, Dushanbe, Tajikistan
| | - Raffaele Pezzani
- Phytotherapy Lab (PhT-Lab), Endocrinology Unit, Department of Medicine (DIMED), University of Padova, Padova, Italy
- AIROB, Associazione Italiana per la Ricerca Oncologica di Base, Padova, Italy
| | - Raffaele Romano
- Department of Agricultural Sciences, University of Napoli Federico II, Portici, Italy
| | - Antonello Santini
- Department of Pharmacy, University of Napoli Federico II, Napoli, Italy
| | - Marek Kieliszek
- Department of Food Biotechnology and Microbiology, Institute of Food Sciences, Warsaw University of Life Sciences-SGGW, Warsaw, Poland
| | - Tooba Khan
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan
| | - Khushbukhat Khan
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan
- Preclinical and Clinical Department, Lahore, Pakistan
| | - Angela Caunii
- "Victor Babes" University of Medicine and Pharmacy Timisoara, Timisoara, Romania
| | - Solomon Habtemariam
- Pharmacognosy Research & Herbal Analysis Services UK, Central Avenue, Chatham-Maritime, Kent, UK
| | - Javad Sharifi-Rad
- Universidad Espíritu Santo, Samborondón, Ecuador
- Centro de Estudios Tecnológicos y Universitarios del Golfo, Veracruz, Mexico
- Department of Medicine, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Monica Butnariu
- University of Life Sciences "King Mihai I" from Timisoara, Timișoara, Romania
| |
Collapse
|
11
|
Li J, Zhao Z, Deng Y, Li X, Zhu L, Wang X, Li L, Li X. Regulatory Roles of Quercetin in Alleviating Fructose-Induced Hepatic Steatosis: Targeting Gut Microbiota and Inflammatory Metabolites. Food Sci Nutr 2025; 13:e4612. [PMID: 39803241 PMCID: PMC11717000 DOI: 10.1002/fsn3.4612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 09/30/2024] [Accepted: 11/01/2024] [Indexed: 01/16/2025] Open
Abstract
While fructose is a key dietary component, concerns have been raised about its potential risks to the liver. This study aimed to assess quercetin's protective effects against fructose-induced mouse hepatic steatosis. Thirty-two male C57BL/6J mice were randomly allocated into four groups: control, high fructose diet (HFrD), HFrD supplemented with low-dose quercetin (HFrD+LQ), and HFrD supplemented with high-dose quercetin (HFrD+HQ). Biochemical, pathological, immune, and metabolic parameters were assessed. Quercetin treatment significantly reduced liver fat percentages in mice on a high fructose diet, with the most notable reduction observed in the HFrD+HQ group. Histological examination confirmed this reduction, revealing diminished lipid droplets and decreased inflammation and steatosis in hepatocytes. Compared to the high fructose group, interleukin-1 β and tumor necrosis factor alpha were significantly decreased, serum aspartate aminotransferase concentrations were markedly reduced, and blood high-density lipoprotein concentrations were substantially elevated after quercetin intervention (p < 0.05). Total bilirubin and triglyceride levels, which were significantly altered following high fructose intervention and reversed after quercetin intervention. Following the administration of 100 mg/kg quercetin, the Firmicutes/Bacteroidetes ratio was significantly reduced compared to the high fructose group. At the genus level, Erysipelotrichaceae_uncultured, Faecalibaculum, Odoribacter, and Allobaculum were significantly decreased (p < 0.05), Lacnospiraceae NK4A136 group, Parabacteroides, and Alloprevotella significantly increased (p < 0.05). However, the 50 mg/kg quercetin treatment only decreased the abundance of Erysipelotrichaceae_uncultured (p < 0.05). In addition, quercetin significantly enhanced the content of propionic acid and total acid (p < 0.05). Moreover, the intestinal flora showed a significant correlation with the hepatic health-related phenotype in mice. Both 50 and 100 mg/kg quercetin treatments significantly mitigated liver fat deposition in mice with fructose-induced hepatic steatosis. However, the higher dose of quercetin (100 mg/kg) demonstrated a more pronounced effect in reducing liver inflammation, likely due to its impact on gut microbiota regulation. This suggests quercetin's potential as a therapeutic agent for fructose-related hepatic steatosis, emphasizing the importance of dose considerations.
Collapse
Affiliation(s)
- Jinjun Li
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro‐Products and Institute of Food SciencesZhejiang Academy of Agricultural SciencesHangzhouChina
- Institute of Food Science, Zhejiang Academy of Agricultural SciencesHangzhouChina
- Key Laboratory of Postharvest Preservation and Processing of Vegetables (Co‐Construction by Ministry and Province)Ministry of Agriculture and Rural AffairsHangzhouChina
| | - Zhiqi Zhao
- Institute of Food Science, Zhejiang Academy of Agricultural SciencesHangzhouChina
| | - Yixuan Deng
- School of MedicineWenzhou Medical University, Chashan University TownWenzhouZhejiangChina
| | - Xinxin Li
- Institute of Food Science, Zhejiang Academy of Agricultural SciencesHangzhouChina
| | - Liying Zhu
- Institute of Food Science, Zhejiang Academy of Agricultural SciencesHangzhouChina
| | - Xin Wang
- Institute of Food Science, Zhejiang Academy of Agricultural SciencesHangzhouChina
| | - Li Li
- Clinical Medical College, Hangzhou Normal UniversityHangzhouChina
| | - Xiaoqiong Li
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro‐Products and Institute of Food SciencesZhejiang Academy of Agricultural SciencesHangzhouChina
- Institute of Food Science, Zhejiang Academy of Agricultural SciencesHangzhouChina
| |
Collapse
|
12
|
Farid MS, Shafique B, Xu R, Łopusiewicz Ł, Zhao C. Potential interventions and interactions of bioactive polyphenols and functional polysaccharides to alleviate inflammatory bowel disease - A review. Food Chem 2025; 462:140951. [PMID: 39213975 DOI: 10.1016/j.foodchem.2024.140951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 08/17/2024] [Accepted: 08/20/2024] [Indexed: 09/04/2024]
Abstract
Inflammatory bowel disease is a multifaceted condition that is influenced by nutritional, microbial, environmental, genetic, psychological, and immunological factors. Polyphenols and polysaccharides have gained recognition for their therapeutic potential. This review emphasizes the biological effects of polyphenols and polysaccharides, and explores their antioxidant, anti-inflammatory, and microbiome-modulating properties in the management of inflammatory bowel disease (IBD). However, polyphenols encounter challenges, such as low stability and low bioavailability in the colon during IBD treatment. Hence, polysaccharide-based encapsulation is a promising solution to achieve targeted delivery, improved bioavailability, reduced toxicity, and enhanced stability. This review also discusses the significance of covalent and non-covalent interactions, and simple and complex encapsulation between polyphenols and polysaccharides. The administration of these compounds in appropriate quantities has proven beneficial in preventing the development of Crohn's disease and ulcerative colitis, ultimately leading to the management of IBD. The use of polyphenols and polysaccharides has been found to reduce histological scores and colon injury associated with IBD, increase the abundance of beneficial microbes, inhibit the development of colitis-associated cancer, promote the production of microbial end-products, such as short-chain fatty acids (SCFAs), and improve anti-inflammatory properties. Despite the combined effects of polyphenols and polysaccharides observed in both in vitro and in vivo studies, further human clinical trials are needed to comprehend their effectiveness on inflammatory bowel disease.
Collapse
Affiliation(s)
| | - Bakhtawar Shafique
- College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China
| | - Rui Xu
- College of Food Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao 066004, China
| | - Łukasz Łopusiewicz
- School of Medical & Health Sciences, University of Economics and Human Sciences in Warsaw, 59 Okopowa Str. Warszawa, 01-043, Poland; Institute of Pharmacy, Department Pharmaceutical Biology, Greifswald University, Friedrich-Ludwig-Jahn-Str. 17, 17489 Greifswald, Germany
| | - Changhui Zhao
- College of Food Science and Engineering, Jilin University, Changchun 130062, China.
| |
Collapse
|
13
|
Anghel AC, Țăranu I, Orțan A, Marcu Spinu S, Dragoi Cudalbeanu M, Rosu PM, Băbeanu NE. Polyphenols and Microbiota Modulation: Insights from Swine and Other Animal Models for Human Therapeutic Strategies. Molecules 2024; 29:6026. [PMID: 39770115 PMCID: PMC11678809 DOI: 10.3390/molecules29246026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/15/2024] [Accepted: 12/17/2024] [Indexed: 01/04/2025] Open
Abstract
High consumption of ultra-processed foods, rich in sugar and unhealthy fats, has been linked to the onset of numerous chronic diseases. Consequently, there has been a growing shift towards a fiber-rich diet, abundant in fruits, vegetables, seeds, and nuts, to enhance longevity and quality of life. The primary bioactive components in these plant-based foods are polyphenols, which exert significant effects on modulating the gastrointestinal microbiota through their antioxidant and anti-inflammatory activities. This modulation has preventive effects on neurodegenerative, metabolic, and cardiovascular diseases, and even cancer. The antimicrobial properties of polyphenols against pathogenic bacteria have significantly reduced the need for antibiotics, thereby lowering the risk of antibiotic resistance. This paper advances the field by offering novel insights into the beneficial effects of polyphenols, both directly through the metabolites produced during digestion and indirectly through changes in the host's gastrointestinal microbiota, uniquely emphasizing swine as a model highly relevant to human health, a topic that, to our knowledge, has not been thoroughly explored in previous reviews. This review also addresses aspects related to both other animal models (mice, rabbits, and rats), and humans, providing guidelines for future research into the benefits of polyphenol consumption. By linking agricultural and biomedical perspectives, it proposes strategies for utilizing these bioactive compounds as therapeutic agents in both veterinary and human health sciences.
Collapse
Affiliation(s)
- Andrei Cristian Anghel
- Faculty of Biotechnologies, University of Agronomic Sciences and Veterinary Medicine of Bucharest, 59 Marasti Boulevard, 011464 Bucharest, Romania; (A.C.A.); (N.E.B.)
- National Research-Development Institute for Animal Biology and Nutrition (IBNA), 1 Calea Bucuresti, 077015 Balotesti, Romania;
| | - Ionelia Țăranu
- National Research-Development Institute for Animal Biology and Nutrition (IBNA), 1 Calea Bucuresti, 077015 Balotesti, Romania;
| | - Alina Orțan
- Faculty of Land Reclamation and Environmental Engineering, University of Agronomic Sciences and Veterinary Medicine of Bucharest, 59 MarastiBoulevard, 011464 Bucharest, Romania; (S.M.S.); (M.D.C.)
| | - Simona Marcu Spinu
- Faculty of Land Reclamation and Environmental Engineering, University of Agronomic Sciences and Veterinary Medicine of Bucharest, 59 MarastiBoulevard, 011464 Bucharest, Romania; (S.M.S.); (M.D.C.)
| | - Mihaela Dragoi Cudalbeanu
- Faculty of Land Reclamation and Environmental Engineering, University of Agronomic Sciences and Veterinary Medicine of Bucharest, 59 MarastiBoulevard, 011464 Bucharest, Romania; (S.M.S.); (M.D.C.)
| | - Petronela Mihaela Rosu
- Faculty of Veterinary Medicine, University of Agronomic Sciences and Veterinary Medicine of Bucharest, 59 Marasti Boulevard, 011464 Bucharest, Romania;
| | - Narcisa Elena Băbeanu
- Faculty of Biotechnologies, University of Agronomic Sciences and Veterinary Medicine of Bucharest, 59 Marasti Boulevard, 011464 Bucharest, Romania; (A.C.A.); (N.E.B.)
| |
Collapse
|
14
|
da C. Pinaffi-Langley AC, Tarantini S, Hord NG, Yabluchanskiy A. Polyphenol-Derived Microbiota Metabolites and Cardiovascular Health: A Concise Review of Human Studies. Antioxidants (Basel) 2024; 13:1552. [PMID: 39765880 PMCID: PMC11673714 DOI: 10.3390/antiox13121552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 12/14/2024] [Accepted: 12/15/2024] [Indexed: 01/11/2025] Open
Abstract
Polyphenols, plant-derived secondary metabolites, play crucial roles in plant stress responses, growth regulation, and environmental interactions. In humans, polyphenols are associated with various health benefits, particularly in cardiometabolic health. Despite growing evidence of polyphenols' health-promoting effects, their mechanisms remain poorly understood due to high interindividual variability in bioavailability and metabolism. Recent research highlights the bidirectional relationship between dietary polyphenols and the gut microbiota, which can influence polyphenol metabolism and, conversely, be modulated by polyphenol intake. In this concise review, we summarized recent advances in this area, with a special focus on isoflavones and ellagitannins and their corresponding metabotypes, and their effect on cardiovascular health. Human observational studies published in the past 10 years provide evidence for a consistent association of isoflavones and ellagitannins and their metabotypes with better cardiovascular risk factors. However, interventional studies with dietary polyphenols or isolated microbial metabolites indicate that the polyphenol-gut microbiota interrelationship is complex and not yet fully elucidated. Finally, we highlighted various pending research questions that will help identify effective targets for intervention with precision nutrition, thus maximizing individual responses to dietary and lifestyle interventions and improving human health.
Collapse
Affiliation(s)
- Ana Clara da C. Pinaffi-Langley
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences, Oklahoma City, OK 73117, USA
- Department of Nutritional Sciences, College of Allied Health, University of Oklahoma Health Sciences, Oklahoma City, OK 73117, USA
| | - Stefano Tarantini
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences, Oklahoma City, OK 73117, USA
- Vascular Cognitive Impairment and Neurodegeneration Program, Department of Neurosurgery, University of Oklahoma Health Sciences, Oklahoma City, OK 73117, USA
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine, Department of Public Health, Semmelweis University, 1085 Budapest, Hungary
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences, Oklahoma City, OK 73104, USA
- Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences, Oklahoma City, OK 73104, USA
| | - Norman G. Hord
- Department of Nutritional Sciences, College of Education and Human Sciences, Oklahoma State University, Stillwater, OK 74075, USA
| | - Andriy Yabluchanskiy
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences, Oklahoma City, OK 73117, USA
- Vascular Cognitive Impairment and Neurodegeneration Program, Department of Neurosurgery, University of Oklahoma Health Sciences, Oklahoma City, OK 73117, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences, Oklahoma City, OK 73104, USA
- Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences, Oklahoma City, OK 73104, USA
| |
Collapse
|
15
|
Jiang C, Luo J, Shao Y. Evaluating the relationship between dietary flavonoids intake and constipation incidence in the general US population. BMC Gastroenterol 2024; 24:455. [PMID: 39696041 DOI: 10.1186/s12876-024-03551-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 12/04/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Dietary adjustment has consistently been regarded as an effective and health way for both the prevention and treatment of constipation. Several researches suggest a significant correlation between dietary flavonoids intake and gut microbiota, while the relationship between dietary flavonoids and constipation has not been reported. The objective of this study is to investigate the relationship between flavonoids intake and constipation. METHODS This cross-sectional analysis was based on data from the National Health and Nutrition Examination Survey (NHANES) collected from 2007 to 2010. The dietary flavonoid and subclasses intake value were obtained from the United States Department of Food and Nutrient Database for Dietary Studies (FNDDS), while constipation was defined using the stool consistency or frequency. Relationships between total and six main flavonoid subclasses intake constipation were investigated using weighted logistic regression approach. RESULTS The study revealed a negative association between isoflavones, anthocyanidins, flavanones, flavones, flavonols, and total flavonoid intake and constipation, with significant p-trends of < 0.05. Following multivariate adjustment, decreased odds of constipation could still be observed in the highest quartiles of anthocyanidins compared with those in the reference quartiles (p-value = 0.03). Ln-transformed anthocyanidins exhibited a statistically significant nonlinear association with constipation, displaying an inverted U-shaped pattern. When anthocyanidins intake exceeded 0.92 mg, the rate of constipation trended downward with increases in anthocyanidins intake. CONCLUSIONS Our study demonstrated that higher dietary flavonoids intake can reduce the incidence of constipation in the adult US population. In addition, the negative association between anthocyanin intake and constipation was more stable compared to other subclasses.
Collapse
Affiliation(s)
- Chenyu Jiang
- Department of Geriatric, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, 318000, China
| | - Jingyao Luo
- Department of Oncology Rehabilitation, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, 318000, China
| | - Yaojian Shao
- Department of Gastroenterology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, 318000, China.
| |
Collapse
|
16
|
Čolić M, Kraljević Pavelić S, Peršurić Ž, Agaj A, Bulog A, Pavelić K. Enhancing the bioavailability and activity of natural antioxidants with nanobubbles and nanoparticles. Redox Rep 2024; 29:2333619. [PMID: 38577911 PMCID: PMC11000614 DOI: 10.1080/13510002.2024.2333619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2024] Open
Abstract
KEY POLICY HIGHLIGHTSNanobubbles and nanoparticles may enhance the polyphenols' bioavailabilityNanobubbles may stimulate the activation of Nrf2 and detox enzymesArmoured oxygen nanobubbles may enhance radiotherapy or chemotherapy effects.
Collapse
Affiliation(s)
| | | | - Željka Peršurić
- Faculty of Medicine, Juraj Dobrila University of Pula, Pula, Croatia
| | - Andrea Agaj
- Faculty of Medicine, Juraj Dobrila University of Pula, Pula, Croatia
| | - Aleksandar Bulog
- Teaching Institute for Public Health of Primorsko-Goranska County, Rijeka, Croatia
- Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Krešimir Pavelić
- Faculty of Medicine, Juraj Dobrila University of Pula, Pula, Croatia
| |
Collapse
|
17
|
Hunt T, Pontifex MG, Vauzour D. (Poly)phenols and brain health - beyond their antioxidant capacity. FEBS Lett 2024; 598:2949-2962. [PMID: 39043619 PMCID: PMC11665953 DOI: 10.1002/1873-3468.14988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 06/07/2024] [Accepted: 07/09/2024] [Indexed: 07/25/2024]
Abstract
(Poly)phenols are a group of naturally occurring phytochemicals present in high amounts in plant food and beverages with various structures and activities. The impact of (poly)phenols on brain function has gained significant attention due to the growing interest in the potential benefits of these dietary bioactive molecules for cognitive health and neuroprotection. This review will therefore summarise the current knowledge related to the impact of (poly)phenols on brain health presenting evidence from both epidemiological and clinical studies. Cellular and molecular mechanisms in relation to the observed effects will also be described, including their impact on the gut microbiota through the modulation of the gut-brain axis. Although (poly)phenols have the potential to modulate the gut-brain axis regulation and influence cognitive function and decline through their interactions with gut microbiota, anti-inflammatory and antioxidant properties, further research, including randomised controlled trials and mechanistic studies, is needed to better understand the underlying mechanisms and establish causal relationships between (poly)phenol intake and brain health.
Collapse
Affiliation(s)
- Thomas Hunt
- Norwich Medical SchoolUniversity of East AngliaNorwichUK
| | | | - David Vauzour
- Norwich Medical SchoolUniversity of East AngliaNorwichUK
| |
Collapse
|
18
|
Cao X, Xu F, Zhao H, Zhang J, Liu C. An extra honey polyphenols-rich diet ameliorates the high-fat diet induced chronic kidney disease via modulating gut microbiota in C57BL/6 mice. Ren Fail 2024; 46:2367700. [PMID: 38938191 PMCID: PMC467112 DOI: 10.1080/0886022x.2024.2367700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 06/07/2024] [Indexed: 06/29/2024] Open
Abstract
Honey is not equivalent to sugar and possess a worldwide health promoting effects such as antioxidant, antibacterial, anti-inflammatory, and hepatoprotective activities. Nevertheless, the potential impacts of honey on high-fat diet induced chronic kidney disease (CKD) and gut microbiota remain to be explored. Herein a high-fat diet was used to induce a mouse CKD model, and analysis was conducted on liver, kidney, spleen indices, tissue morphology, biochemical parameters, CKD related genes, and gut microbial diversity. The results indicated that significant inhibitory effects on renal damage caused by a high-fat diet in mice and improvement in disease symptoms were observed upon honey treatment. Significant changes were also found in serum TC, TG, UA, and BUN as well as the inflammation-related protein TNF-α and IL-6 levels in renal tissues. Gene expression analysis revealed that honey intake closely relates to gut microbiota diversity, which can regulate the composition of gut microbiota, increase microbial diversity, especially Bifidobacteriales and S24_7 and promote the synthesis of short chain fatty acids (SCFAs). In summary, this study suggests that honey has both preventive and therapeutic effects on CKD, which may be associated with its ability to improve microbial composition, increase microbial diversity, and regulate SCFAs levels.
Collapse
Affiliation(s)
- Xirong Cao
- Ministry of Education, Key Laboratory of Surgical Critical Care and Life Support (Xi’an Jiaotong University), Xi’an, Shaanxi, China
- Department of SICU, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Fangrui Xu
- School of Food Science and Technology, Northwest University, Xi’an, China
| | - Haoan Zhao
- School of Food Science and Technology, Northwest University, Xi’an, China
| | - Jingyao Zhang
- Ministry of Education, Key Laboratory of Surgical Critical Care and Life Support (Xi’an Jiaotong University), Xi’an, Shaanxi, China
- Department of SICU, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Chang Liu
- Ministry of Education, Key Laboratory of Surgical Critical Care and Life Support (Xi’an Jiaotong University), Xi’an, Shaanxi, China
- Department of Hepatobiliary, Pancreatic and Liver Transplantation Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| |
Collapse
|
19
|
Rosales TKO, da Silva FFA, Bernardes ES, Paulo Fabi J. Plant-derived polyphenolic compounds: nanodelivery through polysaccharide-based systems to improve the biological properties. Crit Rev Food Sci Nutr 2024; 64:11894-11918. [PMID: 37585699 DOI: 10.1080/10408398.2023.2245038] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/18/2023]
Abstract
Plant-derived polyphenols are naturally occurring compounds widely distributed in plants. They have received greater attention in the food and pharmaceutical industries due to their potential health benefits, reducing the risk of some chronic diseases due to their antioxidant, anti-inflammatory, anticancer, cardioprotective, and neuro-action properties. Polyphenolic compounds orally administered can be used as adjuvants in several treatments but with restricted uses due to chemical instability. The review discusses the different structural compositions of polyphenols and their influence on chemical stability. Despite the potential and wide applications, there is a need to improve the delivery of polyphenolics to target the human intestine without massive chemical modifications. Oral administration of polyphenols is unfeasible due to instability, low bioaccessibility, and limited bioavailability. Nano-delivery systems based on polysaccharides (starch, pectin, chitosan, and cellulose) have been identified as a viable option for oral ingestion, potentiate biological effects, and direct-controlled delivery in specific tissues. The time and dose can be individualized for specific diseases, such as intestinal cancer. This review will address the mechanisms by which polysaccharides-based nanostructured systems can protect against degradation and enhance intestinal permeation, oral bioavailability, and the potential application of polysaccharides as nanocarriers for the controlled and targeted delivery of polyphenolic compounds.
Collapse
Affiliation(s)
- Thiécla Katiane Osvaldt Rosales
- Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Instituto de Pesquisa Energéticas e Nucleares - IPEN, São Paulo, SP, Brazil
| | | | | | - João Paulo Fabi
- Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Food Research Center (FoRC), CEPID-FAPESP (Research, Innovation and Dissemination Centers, São Paulo Research Foundation), São Paulo, SP, Brazil
- Food and Nutrition Research Center (NAPAN), University of São Paulo, São Paulo, SP, Brazil
| |
Collapse
|
20
|
Chakraborty P, Dewanjee S. Unrevealing the mechanisms behind the cardioprotective effect of wheat polyphenolics. Arch Toxicol 2024; 98:3543-3567. [PMID: 39215839 DOI: 10.1007/s00204-024-03850-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 08/19/2024] [Indexed: 09/04/2024]
Abstract
Cardiovascular diseases pose a major threat to both life expectancy and quality of life worldwide, and a concerning level of disease burden has been attained, particularly in middle- and low-income nations. Several drugs presently in use lead to multiple adverse events. Thus, it is urgently needed to develop safe, affordable, and effective management of cardiovascular diseases. Emerging evidence reveals a positive association between polyphenol consumption and cardioprotection. Whole wheat grain and allied products are good sources of polyphenolic compounds bearing enormous cardioprotective potential. Polyphenolic extract of the entire wheat grain contains different phenolic compounds viz. ferulic acid, caffeic acid, chlorogenic acid, p-coumaric acid, sinapic acid, syringic acid, vanillic acid, apigenin, quercetin, luteolin, etc. which exert cardioprotection by reducing oxidative stress and interfering with different toxicological processes. The antioxidant capacity has been thought to exert the cardioprotective mechanism of wheat grain polyphenolics, which predominantly suppresses oxidative stress, inflammation and fibrosis by downregulating several pathogenic signaling events. However, the combined effect of polyphenolics appears to be more prominent than that of a single molecule, which might be attained due to the synergy resulting in multimodal cardioprotective benefits from multiple phenolics. The current article covers the bioaccessibility and possible effects of wheat-derived polyphenolics in protecting against several cardiovascular disorders. This review discusses the mechanistic pharmacology of individual wheat polyphenols on the cardiovascular system. It also highlights the comparative superiority of polyphenolic extracts over a single phenolic.
Collapse
Affiliation(s)
- Pratik Chakraborty
- Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India
| | - Saikat Dewanjee
- Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.
| |
Collapse
|
21
|
Wang Q, Huang H, Yang Y, Yang X, Li X, Zhong W, Wen B, He F, Li J. Reinventing gut health: leveraging dietary bioactive compounds for the prevention and treatment of diseases. Front Nutr 2024; 11:1491821. [PMID: 39502877 PMCID: PMC11534667 DOI: 10.3389/fnut.2024.1491821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 10/07/2024] [Indexed: 11/08/2024] Open
Abstract
The human gut harbors a complex and diverse microbiota essential for maintaining health. Diet is the most significant modifiable factor influencing gut microbiota composition and function, particularly through bioactive compounds like polyphenols, dietary fibers, and carotenoids found in vegetables, fruits, seafood, coffee, and green tea. These compounds regulate the gut microbiota by promoting beneficial bacteria and suppressing harmful ones, leading to the production of key microbiota-derived metabolites such as short-chain fatty acids, bile acid derivatives, and tryptophan metabolites. These metabolites are crucial for gut homeostasis, influencing gut barrier function, immune responses, energy metabolism, anti-inflammatory processes, lipid digestion, and modulation of gut inflammation. This review outlines the regulatory impact of typical bioactive compounds on the gut microbiota and explores the connection between specific microbiota-derived metabolites and overall health. We discuss how dietary interventions can affect disease development and progression through mechanisms involving these metabolites. We examine the roles of bioactive compounds and their metabolites in the prevention and treatment of diseases including inflammatory bowel disease, colorectal cancer, cardiovascular diseases, obesity, and type 2 diabetes mellitus. This study provides new insights into disease prevention and underscores the potential of dietary modulation of the gut microbiota as a strategy for improving health.
Collapse
Affiliation(s)
- Qiurong Wang
- Chengdu Medical College, Chengdu, China
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Hui Huang
- Chengdu Medical College, Chengdu, China
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Ying Yang
- Chengdu Medical College, Chengdu, China
| | - Xianglan Yang
- Pengzhou Branch of the First Affiliated Hospital of Chengdu Medical College, Pengzhou Second People’s Hospital, Chengdu, China
| | - Xuemei Li
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Wei Zhong
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Biao Wen
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Feng He
- Chengdu Medical College, Chengdu, China
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Jun Li
- Chengdu Medical College, Chengdu, China
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| |
Collapse
|
22
|
Connolly D, Minj J, Murphy KM, Solverson PM, Rust BM, Carbonero F. Impact of quinoa and food processing on gastrointestinal health: a narrative review. Crit Rev Food Sci Nutr 2024:1-14. [PMID: 39422522 DOI: 10.1080/10408398.2024.2416476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2024]
Abstract
Due to exceptional nutritional quality, quinoa is an ideal candidate to solve food insecurity in many countries. Quinoa's profile of polyphenols, essential amino acids, and lipids make it ideal for digestive health. How the nutrient profile and bioavailability of quinoa metabolites differs across cooking methods such as heat, pressure, and time employed has yet to be elucidated. The objective of this review is to compile available research pertaining to the impact of various cooking methods on quinoa's nutritional properties with specific emphasis on how those properties affect gut health. Replacing small percentages of wheat flour with quinoa flour in baked bread increases the antioxidant activity, essential amino acids, fiber, minerals, and polyphenols. Extruding quinoa flour reduces amino acid, lipid, and polyphenol content of the raw seed, however direct quinoa and cereal grain extrudate comparisons are absent. Boiling quinoa leads to an increase of dietary fiber as well as exceptional retention of amino acids, lipids, and polyphenols. Baking and extruding with quinoa flour results in less optimal texture due to higher density, however minor substitutions can retain acceptable texture and even improve taste. Future research on quinoa's substitution in common processing methods will create equally desirable, yet more nutritious food products.
Collapse
Affiliation(s)
- Devin Connolly
- Department of Nutrition and Exercise Physiology, Elson Floyd College of Medicine, Washington State University, Spokane, Washington, USA
| | - Jagrani Minj
- Department of Nutrition and Exercise Physiology, Elson Floyd College of Medicine, Washington State University, Spokane, Washington, USA
| | - Kevin M Murphy
- Department of Crop and Soil Science, Washington State University, Pullman, Washington, USA
| | - Patrick M Solverson
- Department of Nutrition and Exercise Physiology, Elson Floyd College of Medicine, Washington State University, Spokane, Washington, USA
| | - Bret M Rust
- Department of Applied Health Science, Indiana University School of Public Health-Bloomington, Bloomington, Indiana, USA
| | - Franck Carbonero
- Department of Nutrition and Exercise Physiology, Elson Floyd College of Medicine, Washington State University, Spokane, Washington, USA
- School of Food Science, Washington State University, Spokane, Washington, USA
| |
Collapse
|
23
|
El-Saadony MT, Yang T, Saad AM, Alkafaas SS, Elkafas SS, Eldeeb GS, Mohammed DM, Salem HM, Korma SA, Loutfy SA, Alshahran MY, Ahmed AE, Mosa WFA, Abd El-Mageed TA, Ahmed AF, Fahmy MA, El-Tarabily MK, Mahmoud RM, AbuQamar SF, El-Tarabily KA, Lorenzo JM. Polyphenols: Chemistry, bioavailability, bioactivity, nutritional aspects and human health benefits: A review. Int J Biol Macromol 2024; 277:134223. [PMID: 39084416 DOI: 10.1016/j.ijbiomac.2024.134223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 06/17/2024] [Accepted: 07/26/2024] [Indexed: 08/02/2024]
Abstract
Polyphenols, including phenolics, alkaloids, and terpenes, are secondary metabolites that are commonly found in fruits, vegetables, and beverages, such as tea, coffee, wine, chocolate, and beer. These compounds have gained considerable attention and market demand because of their potential health benefits. However, their application is limited due to their low absorption rates and reduced tissue distribution efficiency. Engineering polyphenol-protein complexes or conjugates can enhance the antioxidant properties, bioavailability, and stability of polyphenols and improve digestive enzyme hydrolysis, target-specific delivery, and overall biological functions. Complex polyphenols, such as melanin, tannins, and ellagitannins, can promote gut microbiota balance, bolster antioxidant defense, and improve overall human health. Despite these benefits, the safety of polyphenol complexes must be thoroughly evaluated before their use as functional food additives or supplements. This review provides a detailed overview of the types of macromolecular polyphenols, their chemical composition, and their role in food enrichment. The mechanisms by which complex polyphenols act as antioxidative, anti-inflammatory, and anticancer agents have also been discussed.
Collapse
Affiliation(s)
- Mohamed T El-Saadony
- Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt
| | - Tao Yang
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Pharmacy, Hainan Medical University, Haikou, 571199, China
| | - Ahmed M Saad
- Department of Biochemistry, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt
| | - Samar Sami Alkafaas
- Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt
| | - Sara Samy Elkafas
- Production Engineering and Mechanical Design Department, Faculty of Engineering, Menofia University, Shebin El Kom, 32511, Egypt; Faculty of Control System and Robotics, Information Technologies, Mechanics and Optics (ITMO) University, Saint-Petersburg, Russia
| | - Gehad S Eldeeb
- Department of Food Technology, Faculty of Agriculture, Suez Canal University, Ismailia, 41522, Egypt
| | - Dina Mostafa Mohammed
- Nutrition and Food Sciences Department, National Research Centre, Dokki, Giza, 12622, Egypt
| | - Heba M Salem
- Department of Poultry Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Sameh A Korma
- Department of Food Science, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt
| | - Samah A Loutfy
- Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 12211, Egypt
| | - Mohammad Y Alshahran
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, 9088, Saudi Arabia
| | - Ahmed Ezzat Ahmed
- Department of Biology, College of Science, King Khalid University, Abha, 61421, Saudi Arabia
| | - Walid F A Mosa
- Plant Production Department (Horticulture-Pomology), Faculty of Agriculture, Saba Basha, Alexandria University, Alexandria, 21531, Egypt
| | - Taia A Abd El-Mageed
- Soil and Water Department, Faculty of Agriculture, Fayoum University, Fayoum, 63514, Egypt
| | - Atef F Ahmed
- Department of Biology, College of Science, Taif University, Taif, 21944, Saudi Arabia
| | - Mohamed A Fahmy
- Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt
| | | | - Reda M Mahmoud
- Dr Nutrition Pharmaceuticals (DNP), Dubai, 48685, United Arab Emirates
| | - Synan F AbuQamar
- Department of Biology, United Arab Emirates University, Al Ain, 15551, United Arab Emirates.
| | - Khaled A El-Tarabily
- Department of Biology, United Arab Emirates University, Al Ain, 15551, United Arab Emirates; Harry Butler Institute, Murdoch University, Murdoch, 6150, W.A., Australia
| | - José M Lorenzo
- Centro Tecnologico´ de La Carne de Galicia, Rúa Galicia No. 4, Parque Tecnologico de Galicia, San Cibrao das Vinas, Ourense, 32900, Spain; Universidad de Vigo, Area´ de Tecnología de Los Alimentos, Facultad de Ciencias de Ourense, Ourense, 32004, Spain
| |
Collapse
|
24
|
Perz M, Szymanowska D, Kostrzewa-Susłow E. The Influence of Flavonoids with -Br, -Cl Atoms and -NO 2, -CH 3 Groups on the Growth Kinetics and the Number of Pathogenic and Probiotic Microorganisms. Int J Mol Sci 2024; 25:9269. [PMID: 39273218 PMCID: PMC11395712 DOI: 10.3390/ijms25179269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 08/14/2024] [Accepted: 08/24/2024] [Indexed: 09/15/2024] Open
Abstract
The pursuit of novel or modified substances based on a natural origin, like flavonoids, is essential in addressing the increasing number of diseases and bacterial resistance to antibiotics, as well as in maintaining intestinal balance and enhancing overall gut health. The primary goal of this research was to evaluate the impact of specific flavonoid compounds-chalcones, flavanones, and flavones-substituted with -Br, -Cl, -CH3, and -NO2 on both pathogenic and probiotic microorganisms. Additionally, this study aimed to understand these compounds' influence on standardized normal and pathologically altered intestinal microbiomes. 8-Bromo-6-chloroflavone 4'-O-β-D-(4″-O-methyl)-glucopyranoside and 8-bromo-6-chloroflavanone showed the most promising results as bactericidal agents. They significantly limited or inhibited the growth of pathogenic bacteria without adversely affecting the probiotic's growth. Digestion in vitro studies indicated that 6-methyl-8-nitroflavone and 8-bromo-6-chloroflavone positively modulated the gut microbiome by increasing beneficial bacteria and reducing potentially pathogenic microbes. This effect was most notable in microbiomes characteristic of older individuals and those recovering from chemotherapy or antibiotic treatments. This study underscores the therapeutic potential of flavonoid compounds, particularly those with specific halogen and nitro substitutions, in enhancing gut health.
Collapse
Affiliation(s)
- Martyna Perz
- Department of Food Chemistry and Biocatalysis, Faculty of Biotechnology and Food Science, Wrocław University of Environmental and Life Sciences, 50-375 Wrocław, Poland
| | - Daria Szymanowska
- Department of Biotechnology and Food Microbiology, Faculty of Food Science and Nutrition, Poznań University of Life Sciences, 60-627 Poznań, Poland
- Department of Pharmacognosy and Biomaterials, Faculty of Pharmacy, Poznań University of Medical Sciences, 60-806 Poznań, Poland
| | - Edyta Kostrzewa-Susłow
- Department of Food Chemistry and Biocatalysis, Faculty of Biotechnology and Food Science, Wrocław University of Environmental and Life Sciences, 50-375 Wrocław, Poland
| |
Collapse
|
25
|
Munteanu C, Schwartz B. Interactions between Dietary Antioxidants, Dietary Fiber and the Gut Microbiome: Their Putative Role in Inflammation and Cancer. Int J Mol Sci 2024; 25:8250. [PMID: 39125822 PMCID: PMC11311432 DOI: 10.3390/ijms25158250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 07/19/2024] [Accepted: 07/25/2024] [Indexed: 08/12/2024] Open
Abstract
The intricate relationship between the gastrointestinal (GI) microbiome and the progression of chronic non-communicable diseases underscores the significance of developing strategies to modulate the GI microbiota for promoting human health. The administration of probiotics and prebiotics represents a good strategy that enhances the population of beneficial bacteria in the intestinal lumen post-consumption, which has a positive impact on human health. In addition, dietary fibers serve as a significant energy source for bacteria inhabiting the cecum and colon. Research articles and reviews sourced from various global databases were systematically analyzed using specific phrases and keywords to investigate these relationships. There is a clear association between dietary fiber intake and improved colon function, gut motility, and reduced colorectal cancer (CRC) risk. Moreover, the state of health is reflected in the reciprocal and bidirectional relationships among food, dietary antioxidants, inflammation, and body composition. They are known for their antioxidant properties and their ability to inhibit angiogenesis, metastasis, and cell proliferation. Additionally, they promote cell survival, modulate immune and inflammatory responses, and inactivate pro-carcinogens. These actions collectively contribute to their role in cancer prevention. In different investigations, antioxidant supplements containing vitamins have been shown to lower the risk of specific cancer types. In contrast, some evidence suggests that taking antioxidant supplements can increase the risk of developing cancer. Ultimately, collaborative efforts among immunologists, clinicians, nutritionists, and dietitians are imperative for designing well-structured nutritional trials to corroborate the clinical efficacy of dietary therapy in managing inflammation and preventing carcinogenesis. This review seeks to explore the interrelationships among dietary antioxidants, dietary fiber, and the gut microbiome, with a particular focus on their potential implications in inflammation and cancer.
Collapse
Affiliation(s)
- Camelia Munteanu
- Department of Plant Culture, Faculty of Agriculture, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania
| | - Betty Schwartz
- The Institute of Biochemistry, Food Science and Nutrition, The School of Nutritional Sciences, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel
| |
Collapse
|
26
|
Lv J, Jin S, Zhang Y, Zhou Y, Li M, Feng N. Equol: a metabolite of gut microbiota with potential antitumor effects. Gut Pathog 2024; 16:35. [PMID: 38972976 PMCID: PMC11229234 DOI: 10.1186/s13099-024-00625-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 06/28/2024] [Indexed: 07/09/2024] Open
Abstract
An increasing number of studies have shown that the consumption of soybeans and soybeans products is beneficial to human health, and the biological activity of soy products may be attributed to the presence of Soy Isoflavones (SI) in soybeans. In the intestinal tracts of humans and animals, certain specific bacteria can metabolize soy isoflavones into equol. Equol has a similar chemical structure to endogenous estradiol in the human body, which can bind with estrogen receptors and exert weak estrogen effects. Therefore, equol plays an important role in the occurrence and development of a variety of hormone-dependent malignancies such as breast cancer and prostate cancer. Despite the numerous health benefits of equol for humans, only 30-50% of the population can metabolize soy isoflavones into equol, with individual variation in gut microbiota being the main reason. This article provides an overview of the relevant gut microbiota involved in the synthesis of equol and its anti-tumor effects in various types of cancer. It also summarizes the molecular mechanisms underlying its anti-tumor properties, aiming to provide a more reliable theoretical basis for the rational utilization of equol in the field of cancer treatment.
Collapse
Affiliation(s)
- Jing Lv
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Shengkai Jin
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Yuwei Zhang
- Nantong University Medical School, Nantong, China
| | - Yuhua Zhou
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Menglu Li
- Department of Urology, Jiangnan University Medical Center, Wuxi, China.
- Jiangnan University Medical Center, 68 Zhongshan Road, Wuxi, Jiangsu, 214002, China.
| | - Ninghan Feng
- Wuxi School of Medicine, Jiangnan University, Wuxi, China.
- Nantong University Medical School, Nantong, China.
- Department of Urology, Jiangnan University Medical Center, Wuxi, China.
- Jiangnan University Medical Center, 68 Zhongshan Road, Wuxi, Jiangsu, 214002, China.
| |
Collapse
|
27
|
Li Y, Li YJ, Fang X, Chen DQ, Yu WQ, Zhu ZQ. Peripheral inflammation as a potential mechanism and preventive strategy for perioperative neurocognitive disorder under general anesthesia and surgery. Front Cell Neurosci 2024; 18:1365448. [PMID: 39022312 PMCID: PMC11252726 DOI: 10.3389/fncel.2024.1365448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 06/19/2024] [Indexed: 07/20/2024] Open
Abstract
General anesthesia, as a commonly used medical intervention, has been widely applied during surgical procedures to ensure rapid loss of consciousness and pain relief for patients. However, recent research suggests that general anesthesia may be associated with the occurrence of perioperative neurocognitive disorder (PND). PND is characterized by a decline in cognitive function after surgery, including impairments in attention, memory, learning, and executive functions. With the increasing trend of population aging, the burden of PND on patients and society's health and economy is becoming more evident. Currently, the clinical consensus tends to believe that peripheral inflammation is involved in the pathogenesis of PND, providing strong support for further investigating the mechanisms and prevention of PND.
Collapse
Affiliation(s)
- Yuan Li
- Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- Department of Anesthesiology, Mianyang Hospital of Traditional Chinese Medicine, Mianyang, China
| | - Ying-Jie Li
- Department of General Surgery, Mianyang Hospital of Traditional Chinese Medicine, Mianyang, China
| | - Xu Fang
- Department of Anesthesiology, Nanchong Central Hospital, The Second Clinical Medical School of North Sichuan Medical College, Zunyi, China
| | - Dong-Qin Chen
- Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Wan-Qiu Yu
- Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Zhao-Qiong Zhu
- Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- Early Clinical Research Ward of Affiliated Hospital of Zunyi Medical University, Zunyi, China
| |
Collapse
|
28
|
Przewłócka K, Korewo-Labelle D, Berezka P, Karnia MJ, Kaczor JJ. Current Aspects of Selected Factors to Modulate Brain Health and Sports Performance in Athletes. Nutrients 2024; 16:1842. [PMID: 38931198 PMCID: PMC11206260 DOI: 10.3390/nu16121842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 06/10/2024] [Accepted: 06/10/2024] [Indexed: 06/28/2024] Open
Abstract
This review offers a comprehensive evaluation of current aspects related to nutritional strategies, brain modulation, and muscle recovery, focusing on their applications and the underlying mechanisms of physiological adaptation for promoting a healthy brain, not only in athletes but also for recreationally active and inactive individuals. We propose that applying the rule, among others, of good sleep, regular exercise, and a properly balanced diet, defined as "SPARKS", will have a beneficial effect on the function and regeneration processes of the gut-brain-muscle axis. However, adopting the formula, among others, of poor sleep, stress, overtraining, and dysbiosis, defined as "SMOULDER", will have a detrimental impact on the function of this axis and consequently on human health as well as on athletes. Understanding these dynamics is crucial for optimizing brain health and cognitive function. This review highlights the significance of these factors for overall well-being, suggesting that adopting the "SPARKS" approach may benefit not only athletes but also older adults and individuals with health conditions.
Collapse
Affiliation(s)
- Katarzyna Przewłócka
- Division of Physiology, Gdansk University of Physical Education and Sport, 80-336 Gdansk, Poland;
| | - Daria Korewo-Labelle
- Department of Physiology, Faculty of Medicine, Medical University of Gdansk, 80-211 Gdansk, Poland;
| | - Paweł Berezka
- Department of Animal and Human Physiology, Faculty of Biology, University of Gdansk, 80-309 Gdansk, Poland; (P.B.); (M.J.K.)
| | - Mateusz Jakub Karnia
- Department of Animal and Human Physiology, Faculty of Biology, University of Gdansk, 80-309 Gdansk, Poland; (P.B.); (M.J.K.)
| | - Jan Jacek Kaczor
- Department of Animal and Human Physiology, Faculty of Biology, University of Gdansk, 80-309 Gdansk, Poland; (P.B.); (M.J.K.)
| |
Collapse
|
29
|
Martemucci G, Khalil M, Di Luca A, Abdallah H, D’Alessandro AG. Comprehensive Strategies for Metabolic Syndrome: How Nutrition, Dietary Polyphenols, Physical Activity, and Lifestyle Modifications Address Diabesity, Cardiovascular Diseases, and Neurodegenerative Conditions. Metabolites 2024; 14:327. [PMID: 38921462 PMCID: PMC11206163 DOI: 10.3390/metabo14060327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 06/07/2024] [Accepted: 06/07/2024] [Indexed: 06/27/2024] Open
Abstract
Several hallmarks of metabolic syndrome, such as dysregulation in the glucose and lipid metabolism, endothelial dysfunction, insulin resistance, low-to-medium systemic inflammation, and intestinal microbiota dysbiosis, represent a pathological bridge between metabolic syndrome and diabesity, cardiovascular, and neurodegenerative disorders. This review aims to highlight some therapeutic strategies against metabolic syndrome involving integrative approaches to improve lifestyle and daily diet. The beneficial effects of foods containing antioxidant polyphenols, intestinal microbiota control, and physical activity were also considered. We comprehensively examined a large body of published articles involving basic, animal, and human studie, as well as recent guidelines. As a result, dietary polyphenols from natural plant-based antioxidants and adherence to the Mediterranean diet, along with physical exercise, are promising complementary therapies to delay or prevent the onset of metabolic syndrome and counteract diabesity and cardiovascular diseases, as well as to protect against neurodegenerative disorders and cognitive decline. Modulation of the intestinal microbiota reduces the risks associated with MS, improves diabetes and cardiovascular diseases (CVD), and exerts neuroprotective action. Despite several studies, the estimation of dietary polyphenol intake is inconclusive and requires further evidence. Lifestyle interventions involving physical activity and reduced calorie intake can improve metabolic outcomes.
Collapse
Affiliation(s)
| | - Mohamad Khalil
- Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Medical School, 70121 Bari, Italy;
| | - Alessio Di Luca
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, 70126 Bari, Italy; (A.D.L.); (A.G.D.)
| | - Hala Abdallah
- Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Medical School, 70121 Bari, Italy;
| | | |
Collapse
|
30
|
Chen F, Liu P. Effects of Chinese medical care on elderly patients with constipation. Minerva Gastroenterol (Torino) 2024; 70:258-261. [PMID: 37326628 DOI: 10.23736/s2724-5985.23.03442-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Affiliation(s)
- Fei Chen
- Department Comprehensive Ward2, Zhejiang Hospital, Hangzhou, China
| | - Peipei Liu
- Department Comprehensive Ward2, Zhejiang Hospital, Hangzhou, China -
| |
Collapse
|
31
|
Jaberi KR, Alamdari-palangi V, Savardashtaki A, Vatankhah P, Jamialahmadi T, Tajbakhsh A, Sahebkar A. Modulatory Effects of Phytochemicals on Gut-Brain Axis: Therapeutic Implication. Curr Dev Nutr 2024; 8:103785. [PMID: 38939650 PMCID: PMC11208951 DOI: 10.1016/j.cdnut.2024.103785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 04/23/2024] [Accepted: 05/17/2024] [Indexed: 06/29/2024] Open
Abstract
This article explores the potential therapeutic implications of phytochemicals on the gut-brain axis (GBA), which serves as a communication network between the central nervous system and the enteric nervous system. Phytochemicals, which are compounds derived from plants, have been shown to interact with the gut microbiota, immune system, and neurotransmitter systems, thereby influencing brain function. Phytochemicals such as polyphenols, carotenoids, flavonoids, and terpenoids have been identified as having potential therapeutic implications for various neurological disorders. The GBA plays a critical role in the development and progression of various neurological disorders, including Parkinson's disease, multiple sclerosis, depression, anxiety, and autism spectrum disorders. Dysbiosis, or an imbalance in gut microbiota composition, has been associated with a range of neurological disorders, suggesting that modulating the gut microbiota may have potential therapeutic implications for these conditions. Although these findings are promising, further research is needed to elucidate the optimal use of phytochemicals in neurological disorder treatment, as well as their potential interactions with other medications. The literature review search was conducted using predefined search terms such as phytochemicals, gut-brain axis, neurodegenerative, and Parkinson in PubMed, Embase, and the Cochrane library.
Collapse
Affiliation(s)
- Khojasteh Rahimi Jaberi
- Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Vahab Alamdari-palangi
- Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Savardashtaki
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
- Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Pooya Vatankhah
- Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Tannaz Jamialahmadi
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Tajbakhsh
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| |
Collapse
|
32
|
Lei W, Qi M, Tan P, Yang S, Fan L, Li H, Gao Z. Impact of polyphenol-loaded edible starch nanomaterials on antioxidant capacity and gut microbiota. Int J Biol Macromol 2024; 265:130979. [PMID: 38508552 DOI: 10.1016/j.ijbiomac.2024.130979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 03/04/2024] [Accepted: 03/16/2024] [Indexed: 03/22/2024]
Abstract
Starch nanoparticles (SNPs) have the capability to adsorb polyphenol components from apple pomace efficiently, forming bound polyphenols (P-SNPs). These bound polyphenols may have potential bioactivities to affect human health positively. Therefore, in-depth in vivo observation of the antioxidant activity and evaluation of its gut microbiota regulatory function are essential. The results revealed that P-SNPs indicated significant scavenging abilities against DPPH, ABTS, and hydroxyl radicals. Furthermore, the nanomaterials exhibited non-toxic properties, devoid of hepatorenal and intestinal damage, while concurrently stimulating the production of short-chain fatty acids (SCFAs) within the gastrointestinal tract. Notably, P-SNPs significantly enhanced antioxidant capacity in serum, liver, and kidney tissues, fostering the proliferation of beneficial bacteria (Lactobacillus, Bacillus, norank_f__Muribaculaceae) while suppressing pathogenic bacterial growth (Helicobacter, Odoribacter). This study proposes a novel research concept for the scientific use of polyphenols in promoting gut health.
Collapse
Affiliation(s)
- Wenzhi Lei
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, People's Republic of China
| | - Maodong Qi
- College of Life Sciences, Northwest A&F University, 712100 Yangling, Shaanxi, People's Republic of China
| | - Pei Tan
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, People's Republic of China
| | - Siqi Yang
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, People's Republic of China
| | - Lingjia Fan
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, People's Republic of China
| | - Hongcai Li
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, People's Republic of China
| | - Zhenpeng Gao
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, People's Republic of China.
| |
Collapse
|
33
|
Hu J, Mesnage R, Tuohy K, Heiss C, Rodriguez-Mateos A. (Poly)phenol-related gut metabotypes and human health: an update. Food Funct 2024; 15:2814-2835. [PMID: 38414364 DOI: 10.1039/d3fo04338j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/29/2024]
Abstract
Dietary (poly)phenols have received great interest due to their potential role in the prevention and management of non-communicable diseases. In recent years, a high inter-individual variability in the biological response to (poly)phenols has been demonstrated, which could be related to the high variability in (poly)phenol gut microbial metabolism existing within individuals. An interplay between (poly)phenols and the gut microbiota exists, with (poly)phenols being metabolised by the gut microbiota and their metabolites modulating gut microbiota diversity and composition. A number of (poly)phenol metabolising phenotypes or metabotypes have been proposed, however, potential metabotypes for most (poly)phenols have not been investigated, and the relationship between metabotypes and human health remains ambiguous. This review presents updated knowledge on the reciprocal interaction between (poly)phenols and the gut microbiome, associated gut metabotypes, and subsequent impact on human health.
Collapse
Affiliation(s)
- Jiaying Hu
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
| | - Robin Mesnage
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
- Buchinger Wilhelmi Clinic, Überlingen, Germany
| | - Kieran Tuohy
- School of Food Science and Nutrition, Faculty of Environment, University of Leeds, Leeds, UK
| | - Christian Heiss
- Department of Clinical and Experimental Medicine, Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK
| | - Ana Rodriguez-Mateos
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
| |
Collapse
|
34
|
Wang L, Li M, Gu Y, Shi J, Yan J, Wang X, Li B, Wang B, Zhong W, Cao H. Dietary flavonoids-microbiota crosstalk in intestinal inflammation and carcinogenesis. J Nutr Biochem 2024; 125:109494. [PMID: 37866426 DOI: 10.1016/j.jnutbio.2023.109494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 02/20/2023] [Accepted: 10/17/2023] [Indexed: 10/24/2023]
Abstract
Colorectal cancer (CRC) is currently the third leading cancer and commonly develops from chronic intestinal inflammation. A strong association was found between gut microbiota and intestinal inflammation and carcinogenic risk. Flavonoids, which are abundant in vegetables and fruits, can inhibit inflammation, regulate gut microbiota, protect gut barrier integrity, and modulate immune cell function, thereby attenuating colitis and preventing carcinogenesis. Upon digestion, about 90% of flavonoids are transported to the colon without being absorbed in the small intestine. This phenomenon increases the abundance of beneficial bacteria and enhances the production of short-chain fatty acids. The gut microbe further metabolizes these flavonoids. Interestingly, some metabolites of flavonoids play crucial roles in anti-inflammation and anti-tumor effects. This review summarizes the modulatory effect of flavonoids on gut microbiota and their metabolism by intestinal microbe under disease conditions, including inflammatory bowel disease, colitis-associated cancer (CAC), and CRC. We focus on dietary flavonoids and microbial interactions in intestinal mucosal barriers as well as intestinal immune cells. Results provide novel insights to better understand the crosstalk between dietary flavonoids and gut microbiota and support the standpoint that dietary flavonoids prevent intestinal inflammation and carcinogenesis.
Collapse
Affiliation(s)
- Lei Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China; Department of Gastroenterology and Hepatology, The Affiliated Hospital of Chengde Medical College, Hebei, China
| | - Mengfan Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Yu Gu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Junli Shi
- Department of Gastroenterology and Hepatology, The Affiliated Hospital of Chengde Medical College, Hebei, China
| | - Jing Yan
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China; Department of Nutrition, the Second Affiliated Hospital, Air Force Medical University, Xi'an, China
| | - Xin Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Bingqing Li
- Department of Gastroenterology and Hepatology, The Affiliated Hospital of Chengde Medical College, Hebei, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Weilong Zhong
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
| |
Collapse
|
35
|
Rodriguez-Mateos A, Le Sayec M, Cheok A. Dietary (poly)phenols and cardiometabolic health: from antioxidants to modulators of the gut microbiota. Proc Nutr Soc 2024:1-11. [PMID: 38316606 DOI: 10.1017/s0029665124000156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2024]
Abstract
(Poly)phenols are plant secondary metabolites widely abundant in plant foods and beverages comprising a very large number of compounds with diverse structure and biological activities. Accumulating evidence indicates that these compounds exert beneficial effects against cardiometabolic diseases, and this review will provide a summary of current knowledge in this area. Epidemiological and clinical data collectively suggest that intake of flavonoids reduces the risk of cardiovascular disease (CVD), with the evidence being particularly strong for the flavan-3-ol subclass. However, to provide adequate dietary recommendations, a better understanding of their estimated content in foods and intake among the general public is needed. Regarding mechanisms of action, we now know that it is unlikely that (poly)phenols act as direct antioxidants in vivo, as it was hypothesised for decades with the popularity of in vitro antioxidant capacity assays. One of the reasons is that upon ingestion, (poly)phenols are extensively metabolised into a wide array of circulating metabolites with different bioactivities than their precursors. Well-conducted in vitro and in vivo studies and human nutrigenomic analysis have revealed new molecular targets that may be underlying the health benefits of (poly)phenols, such as the nitric oxide pathway. Recently, a bi-directional relationship was established between (poly)phenols and the gut microbiota, suggesting that individual gut microbial metabolising capacity may be a key factor explaining the variability in the cardiometabolic response to (poly)phenols. Future research is needed to elucidate which are the key factors affecting such capacity, and whether it can be modulated, along with the mechanisms of action.
Collapse
Affiliation(s)
- Ana Rodriguez-Mateos
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Melanie Le Sayec
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Alex Cheok
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
| |
Collapse
|
36
|
Liu P, Tan XY, Zhang HQ, Su KL, Shang EX, Xiao QL, Guo S, Duan JA. Optimal compatibility proportional screening of Trichosanthis Pericarpium - Trichosanthis Radix and its anti - Inflammatory components effect on experimental zebrafish and coughing mice. JOURNAL OF ETHNOPHARMACOLOGY 2024; 319:117096. [PMID: 37634750 DOI: 10.1016/j.jep.2023.117096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 08/21/2023] [Accepted: 08/24/2023] [Indexed: 08/29/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The herbal pair of Trichosanthis Pericarpium (TP) - Trichosanthis Radix (TR) can be seen in the famous formula "Beimu Gualou San". It is a commonly selected combination of medicinal herbs for the treatment of cough with lung heat. Both drugs are derived from Trichosanthes kirilowii Maxim, a medicinal plant known for its ability to clear heat, resolve phlegm, produce saliva, and alleviate dryness. However, the optimal combination ratio and active ingredients of TP-TR have yet to be determined. AIM OF THE STUDY This study aims to investigate the optimal combination ratio of TP-TR and its anti-inflammatory active ingredients in cough treatment. MATERIALS AND METHODS A zebrafish (Danio rerio) inflammatory injury model and response surface method were applied in the present study to determine the appropriate proportion of TP-TR. Chemical constituents in TP-TR were identified using HPLC-ELSD and UPLC-MS/MS methods. Subsequently, a cough mouse model was created using an ammonia solution to evaluate the effectiveness of the optimal TP-TR ratio. Network pharmacology and intestinal flora sequencing were used to validate the anti-inflammatory components of TP-TR. RESULTS The herbal pair of TP - TR at the ratio of 1:2 showed an optimal anti-inflammatory effect, with a composite inflammatory factor score of 119.645 in the zebrafish experiment. TP-TR combination facilitated the dissolution of glutamine, inosine, cytosine, isoquercetin, and other substances. In the animal model, the TP-TR (1:2) treatment significantly reduced the frequency of coughs and prolonged cough latency compared to the model group. Results of the network pharmacology indicated that inflammatory-related factors such as TLR4, STAT3, EGFR, and AKT1 played crucial roles in cough treatment with TP-TR, consistent with the validation experiment. The 16s rDNA sequencing results revealed a significant increase in the abundance of Clostridia_UCG-014, Lachnospiraceae, Christenella, Ruminococcus, and other species in the intestinal tract of mice after modelling. TP-TR (1:2) reduced the abundance of pro-inflammatory flora such as Clostridium_UCG-014 and Lachnospira, which were closely associated with L-lysine and trans-4-hydroxy-L-proline present in TP-TR according to correlation analysis. CONCLUSION TP-TR may promote the dissolution of glutamine, thymidine, inosine, cytosine, isoquercetin, and other components through their combination, thereby regulating the abundance of Clostridium_UCG-014 and Lachnospira and exerting an antitussive effect. This study, for the first time, showed that TP-TR at a 1:2 ratio exhibits superior anti-inflammatory effects. In addition to inflammatory mediators like EGFR, TLR4, AKT1, and STAT3, gut microbes could also serve as potential regulatory targets of TP-TR in the treatment of cough. 2'-Deoxyguanosine monohydrate, L-lysine, L-leucine, γ-aminobutyric acid, L-valine, L-tryptophan, L-proline, trans-4-hydroxy-L-proline, L-methionine, uridine, 2'-deoxyinosine, guanosine, cucurbitacin B and cucurbitacin D were identified as its anti-inflammatory active ingredients.
Collapse
Affiliation(s)
- Pei Liu
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Xiao-Ying Tan
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Huang-Qin Zhang
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210028, China
| | - Ke-Lei Su
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210028, China
| | - Er-Xin Shang
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Qing-Ling Xiao
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210028, China
| | - Sheng Guo
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Jin-Ao Duan
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| |
Collapse
|
37
|
Moriki D, Koumpagioti D, Francino MP, Rufián-Henares JÁ, Kalogiannis M, Priftis KN, Douros K. How Different Are the Influences of Mediterranean and Japanese Diets on the Gut Microbiome? Endocr Metab Immune Disord Drug Targets 2024; 24:1733-1745. [PMID: 38243975 DOI: 10.2174/0118715303261069231124092259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 10/12/2023] [Accepted: 10/17/2023] [Indexed: 01/22/2024]
Abstract
The gut microbiome is a complex ecosystem, mainly composed of bacteria, that performs essential functions for the host. Its composition is determined by many factors; however, diet has emerged as a key regulator. Both the Mediterranean (MD) and Japanese (JD) diets have been associated with significant health benefits and are therefore considered healthy dietary patterns. Both are plant-based diets and although they have much in common, they also have important differences mainly related to total calorie intake and the consumption of specific foods and beverages. Thus, it has been hypothesized that they exert their beneficial properties through different nutrients and bioactive compounds that interact with gut microbes and induce specific changes on gut metabolic pathways. In this review, we present current data on the effects of the MD and JD on the gut microbiome. Furthermore, we aim to examine whether there are differences or shared effects on the gut microbiome of people who adhere to these dietary patterns.
Collapse
Affiliation(s)
- Dafni Moriki
- Allergology and Pulmonology Unit, 3rd Pediatric Department, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - Despoina Koumpagioti
- Department of Nursing, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Maria Pilar Francino
- Department of Genomics and Health, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valencia (FISABIO), 46020 Valencia, Spain
- CIBER en Epidemiología y Salud Pública, 28029 Madrid, Spain
| | - José Ángel Rufián-Henares
- Departamento de Nutrición y Bromatología, Instituto de Nutrición y Tecnología de los Alimentos, Centro de Investigación Biomédica, Universidad de Granada, 18071 Granada, Spain
- Instituto de Investigación Biosanitaria ibs. GRANADA, Universidad de Granada, 18071 Granada, Spain
| | - Michalis Kalogiannis
- Allergology and Pulmonology Unit, 3rd Pediatric Department, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - Kostas N Priftis
- Allergology and Pulmonology Unit, 3rd Pediatric Department, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - Konstantinos Douros
- Allergology and Pulmonology Unit, 3rd Pediatric Department, National and Kapodistrian University of Athens, 12462 Athens, Greece
| |
Collapse
|
38
|
Xu L, Tang Z, Herrera-Balandrano DD, Qiu Z, Li B, Yang Y, Huang W. In vitro fermentation characteristics of blueberry anthocyanins and their impacts on gut microbiota from obese human. Food Res Int 2024; 176:113761. [PMID: 38163698 DOI: 10.1016/j.foodres.2023.113761] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 11/06/2023] [Accepted: 11/22/2023] [Indexed: 01/03/2024]
Abstract
It has been demonstrated that the gut microbiota may play an important intermediary role in anthocyanins' beneficial impacts on obesity. However, the microbe-related anti-obesity mechanism of blueberry anthocyanins remains unclear. In this study, the interactions between blueberry anthocyanin extracts (BAE) and gut microbiota from obese humans were explored using an in vitro fermentation model. Due to hydrolysis and metabolism by the microbiota, the contents of blueberry anthocyanins are reduced during fermentation. It was demonstrated that both aglycones and glycosides affected the degradation rate. The microbial composition evaluation revealed that BAE could alleviate obesity by promoting the colonization of probiotics such as Lachnospiraceae_UCG-004 and Bacteroides, as well as inhibiting the proliferation of harmful bacteria including Escherichia-Shigella, Clostridium_sensu_stricto_1, and Klebsiella. Blueberry anthocyanin extracts facilitate the production of short-chain fatty acids (SCFAs), which is beneficial for obesity control. The relationship between blueberry anthocyanins, gut microbiota, and SCFAs was further investigated. Overall, this data provides new insights into the positive interaction between blueberry anthocyanins and gut microbiota in obese humans.
Collapse
Affiliation(s)
- Lujing Xu
- Institute of Agro-Product Processing, Jiangsu Academy of Agricultural Sciences, Nanjing, 210014, PR China.
| | - Zhaocheng Tang
- Provincial Key Laboratory of Agrobiology and Institute of Germplasm Resources and Biotechnology, Jiangsu Academy of Agricultural Sciences, Nanjing, 210014, PR China.
| | | | - Zeyu Qiu
- Provincial Key Laboratory of Agrobiology and Institute of Germplasm Resources and Biotechnology, Jiangsu Academy of Agricultural Sciences, Nanjing, 210014, PR China.
| | - Bin Li
- College of Food Science, Shenyang Agricultural University, Liaoning 110866, PR China.
| | - Yiyun Yang
- Zhejiang Lanmei Technology Co., Ltd, Zhuji 311899, PR China.
| | - Wuyang Huang
- Institute of Agro-Product Processing, Jiangsu Academy of Agricultural Sciences, Nanjing, 210014, PR China.
| |
Collapse
|
39
|
Kim CS. Roles of Diet-Associated Gut Microbial Metabolites on Brain Health: Cell-to-Cell Interactions between Gut Bacteria and the Central Nervous System. Adv Nutr 2024; 15:100136. [PMID: 38436218 PMCID: PMC10694655 DOI: 10.1016/j.advnut.2023.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 09/21/2023] [Accepted: 10/26/2023] [Indexed: 03/05/2024] Open
Abstract
Gut microbiota have crucial effects on brain function via the gut-brain axis. Growing evidence suggests that this interaction is mediated by signaling molecules derived from dietary components metabolized by the intestinal microbiota. Although recent studies have provided a substantial understanding of the cell-specific effects of gut microbial molecules in gut microbiome-brain research, further validation is needed. This review presents recent findings on gut microbiota-derived dietary metabolites that enter the systemic circulation and influence the cell-to-cell interactions between gut microbes and cells in the central nervous system (CNS), particularly microglia, astrocytes, and neuronal cells, ultimately affecting cognitive function, mood, and behavior. Specifically, this review highlights the roles of metabolites produced by the gut microbiota via dietary component transformation, including short-chain fatty acids, tryptophan metabolites, and bile acid metabolites, in promoting the function and maturation of brain cells and suppressing inflammatory signals in the CNS. We also discuss future directions for gut microbiome-brain research, focusing on diet-induced microbial metabolite-based therapies as possible novel approaches to mental health treatment.
Collapse
Affiliation(s)
- Chong-Su Kim
- Department of Food and Nutrition, College of Natural Information Sciences, Dongduk Women's University, Seoul 02748, Republic of Korea.
| |
Collapse
|
40
|
Przeor M. How Does In Vitro Digestion Change the Amount of Phenolics in Morus alba L. Leaf? Analysis of Preparations and Infusions. Metabolites 2024; 14:31. [PMID: 38248834 PMCID: PMC10818460 DOI: 10.3390/metabo14010031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 12/28/2023] [Accepted: 12/29/2023] [Indexed: 01/23/2024] Open
Abstract
The application of Morus alba L. in traditional oriental medicine and cuisine has resulted in numerous studies on its health-promoting effects. However, if the process is not monitored by the manufacturers, the processing of the leaves alters the obtained health-promoting properties and results in different health qualities in the final composition of dietary supplements. This article aims to analyze changes (using the HPLC/DAD method) in the proposed conditioned mulberry leaves in terms of key compounds (phenolic acids and flavonols) responsible for antioxidant activity after being digested in in vitro conditions. The analyzed material was leaves of white mulberry (Morus alba L.) cv. Żółwińska wielkolistna, conditioned (1-4 h) and non-conditioned. The conditioning process of mulberry proposed here, e.g., for industry production, resulted in variable transformations of polyphenols during in vitro digestion. For many polyphenols, especially those shown in the highest amounts, significant correlations were found between their content and conditioning, as well as the stage of digestion. In the case of mulberry infusions, the amounts of individual polyphenols were several times lower than in the preparations, which was due to the degree of dilution. Their amounts tended to decrease in the course of digestion. Taking this into account, it seems justified to continue research on the in vivo bioavailability of bioactive components from conditioned Morus alba L. leaves.
Collapse
Affiliation(s)
- Monika Przeor
- Department of Gastronomy Sciences and Functional Foods, Poznań University of Life Sciences, Wojska Polskiego 31, 60-624 Poznań, Poland
| |
Collapse
|
41
|
Chang J, Huang C, Li S, Jiang X, Chang H, Li M. Research Progress Regarding the Effect and Mechanism of Dietary Polyphenols in Liver Fibrosis. Molecules 2023; 29:127. [PMID: 38202710 PMCID: PMC10779665 DOI: 10.3390/molecules29010127] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 12/02/2023] [Accepted: 12/18/2023] [Indexed: 01/12/2024] Open
Abstract
The development of liver fibrosis is a result of chronic liver injuries may progress to liver cirrhosis and liver cancer. In recent years, liver fibrosis has become a major global problem, and the incidence rate and mortality are increasing year by year. However, there are currently no approved treatments. Research on anti-liver-fibrosis drugs is a top priority. Dietary polyphenols, such as plant secondary metabolites, have remarkable abilities to reduce lipid metabolism, insulin resistance and inflammation, and are attracting more and more attention as potential drugs for the treatment of liver diseases. Gradually, dietary polyphenols are becoming the focus for providing an improvement in the treatment of liver fibrosis. The impact of dietary polyphenols on the composition of intestinal microbiota and the subsequent production of intestinal microbial metabolites has been observed to indirectly modulate signaling pathways in the liver, thereby exerting regulatory effects on liver disease. In conclusion, there is evidence that dietary polyphenols can be therapeutically useful in preventing and treating liver fibrosis, and we highlight new perspectives and key questions for future drug development.
Collapse
Affiliation(s)
- Jiayin Chang
- Department of Pharmacy, Baotou Medical College, Baotou 014040, China; (J.C.); (C.H.); (S.L.); (X.J.)
| | - Congying Huang
- Department of Pharmacy, Baotou Medical College, Baotou 014040, China; (J.C.); (C.H.); (S.L.); (X.J.)
| | - Siqi Li
- Department of Pharmacy, Baotou Medical College, Baotou 014040, China; (J.C.); (C.H.); (S.L.); (X.J.)
| | - Xiaolei Jiang
- Department of Pharmacy, Baotou Medical College, Baotou 014040, China; (J.C.); (C.H.); (S.L.); (X.J.)
| | - Hong Chang
- Department of Pharmacy, Baotou Medical College, Baotou 014040, China; (J.C.); (C.H.); (S.L.); (X.J.)
| | - Minhui Li
- Department of Pharmacy, Baotou Medical College, Baotou 014040, China; (J.C.); (C.H.); (S.L.); (X.J.)
- Inner Mongolia Autonomous Region Hospital of Traditional Chinese Medicine, Hohhot 010020, China
- Inner Mongolia Key Laboratory of Characteristic Geoherbs Resources Protection and Utilization, Baotou 014040, China
| |
Collapse
|
42
|
Choi SR, Lee H, Singh D, Cho D, Chung JO, Roh JH, Kim WG, Lee CH. Bidirectional Interactions between Green Tea (GT) Polyphenols and Human Gut Bacteria. J Microbiol Biotechnol 2023; 33:1317-1328. [PMID: 37435870 PMCID: PMC10619559 DOI: 10.4014/jmb.2306.06014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 06/26/2023] [Indexed: 07/13/2023]
Abstract
Green tea (GT) polyphenols undergo extensive metabolism within gastrointestinal tract (GIT), where their derivatives compounds potentially modulate the gut microbiome. This biotransformation process involves a cascade of exclusive gut microbial enzymes which chemically modify the GT polyphenols influencing both their bioactivity and bioavailability in host. Herein, we examined the in vitro interactions between 37 different human gut microbiota and the GT polyphenols. UHPLC-LTQ-Orbitrap-MS/MS analysis of the culture broth extracts unravel that genera Adlercreutzia, Eggerthella and Lactiplantibacillus plantarum KACC11451 promoted C-ring opening reaction in GT catechins. In addition, L. plantarum also hydrolyzed catechin galloyl esters to produce gallic acid and pyrogallol, and also converted flavonoid glycosides to their aglycone derivatives. Biotransformation of GT polyphenols into derivative compounds enhanced their antioxidant bioactivities in culture broth extracts. Considering the effects of GT polyphenols on specific growth rates of gut bacteria, we noted that GT polyphenols and their derivate compounds inhibited most species in phylum Actinobacteria, Bacteroides, and Firmicutes except genus Lactobacillus. The present study delineates the likely mechanisms involved in the metabolism and bioavailability of GT polyphenols upon exposure to gut microbiota. Further, widening this workflow to understand the metabolism of various other dietary polyphenols can unravel their biotransformation mechanisms and associated functions in human GIT.
Collapse
Affiliation(s)
- Se Rin Choi
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea
| | - Hyunji Lee
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea
| | - Digar Singh
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea
| | - Donghyun Cho
- Amorepacific R&I Center, Yonggu-daero, Yongin, Republic of Korea
| | - Jin-Oh Chung
- Amorepacific R&I Center, Yonggu-daero, Yongin, Republic of Korea
| | - Jong-Hwa Roh
- Amorepacific R&I Center, Yonggu-daero, Yongin, Republic of Korea
| | - Wan-Gi Kim
- Amorepacific R&I Center, Yonggu-daero, Yongin, Republic of Korea
| | - Choong Hwan Lee
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea
- Research Institute for Bioactive-Metabolome Network, Konkuk University, Seoul 05029, Republic of Korea
| |
Collapse
|
43
|
Seong SH, Kim SH, Ryu JH, Jeong JW, Jung HA, Choi JS. Effects of Icariin and Its Metabolites on GPCR Regulation and MK-801-Induced Schizophrenia-Like Behaviors in Mice. Molecules 2023; 28:7300. [PMID: 37959720 PMCID: PMC10647531 DOI: 10.3390/molecules28217300] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/24/2023] [Accepted: 10/26/2023] [Indexed: 11/15/2023] Open
Abstract
Icariin, a major bioactive compound found in the Epimedium genus, has been reported to exert protective effects against neurodegenerative disorders. In the current study, we aimed to investigate the regulatory effect of icariin and its active metabolites (icariside II and icaritin) against prime G-protein-coupled receptor targets, considering their association with neuronal disorders. Icariside II exhibited selective agonist activity towards the dopamine D3 receptor (D3R), with half-maximal effective concentrations of 13.29 μM. Additionally, they effectively inhibited the specific binding of radioligands to D3R. Molecular docking analysis revealed that icariside II potentially exerts its agonistic effect through hydrogen-bonding interaction with Asp110 of the D3R, accompanied by negative binding energy. Conversely, icaritin demonstrated selective antagonist effects on the muscarinic acetylcholine M2 receptor (M2R). Radioligand binding assay and molecular docking analysis identified icaritin as an orthosteric ligand for M2R. Furthermore, all three compounds, icariin and its two metabolites, successfully mitigated MK-801-induced schizophrenia-like symptoms, including deficits in prepulse inhibition and social interaction, in mice. In summary, these findings highlight the potential of icariin and its metabolites as promising lead structures for the discovery of new drugs targeting cognitive and neurodegenerative disorders.
Collapse
Affiliation(s)
- Su Hui Seong
- Division of Natural Products Research, Honam National Institute of Biological Resources, Mokpo 58762, Republic of Korea; (S.H.S.); (J.-W.J.)
| | - Seo Hyun Kim
- Division of Research Management, Honam National Institute of Biological Resources, Mokpo 58762, Republic of Korea;
| | - Jong Hoon Ryu
- Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul 02447, Republic of Korea;
| | - Jin-Woo Jeong
- Division of Natural Products Research, Honam National Institute of Biological Resources, Mokpo 58762, Republic of Korea; (S.H.S.); (J.-W.J.)
| | - Hyun Ah Jung
- Department of Food Science and Human Nutrition, Jeonbuk National University, Jeonju 54896, Republic of Korea
| | - Jae Sue Choi
- Department of Food and Life Science, Pukyong National University, Busan 48513, Republic of Korea
| |
Collapse
|
44
|
Vega-Rivera NM, González-Trujano ME, Luna-Angula A, Sánchez-Chapul L, Estrada-Camarena E. Antidepressant-like effects of the Punica granatum and citalopram combination are associated with structural changes in dendritic spines of granule cells in the dentate gyrus of rats. Front Pharmacol 2023; 14:1211663. [PMID: 37900157 PMCID: PMC10613096 DOI: 10.3389/fphar.2023.1211663] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 08/31/2023] [Indexed: 10/31/2023] Open
Abstract
Introduction: Natural products such as phytoestrogens-enriched foods or supplements have been considered as an alternative therapy to reduce depressive symptoms associated with menopause. It is known that the aqueous extract of Punica granatum (AE-PG) exerts antidepressant-like effects by activating β-estrogen receptors and facilitates the antidepressant response of the clinical drug citalopram (CIT). However, the effects on neuroplasticity are unknown. Objectvie investigated the antidepressant-like response of combining AE-PG and CIT at sub-optimal doses, analyzing their effects on the formation and maturation of dendrite spines in granule cells as well as on the dendrite complexity. Methods: Ovariectomized Wistar rats (3-month-old) were randomly assigned to one of the following groups: A) control (saline solution as vehicle of CIT and AE-PG, B) AE-PG at a sub-threshold dose (vehicle of CIT plus AE-PG at 0.125 mg/kg), C) CIT at a sub-threshold dose (0.77 mg/kg plus vehicle of AE-PG), and D) a combination of CIT plus AE-PG (0.125 mg/kg and 0.77 mg/kg, respectively). All rats were treated intraperitoneally for 14 days. Antidepressant-like effects were evaluated using the force swimming test test (FST). The complexity of dendrites and the number and morphology of dendrite spines of neurons were assessed in the dentate gyrus after Golgi-Cox impregnation. The expressions of the mature brain-derived neurotrophic factor (mBDNF) in plasma and of mBDNF and synaptophysin in the hippocampus, as markers of synaptogenesis, were also determined. Results: Administration of CIT combined with AE-PG, but not alone, induced a significant antidepressant-like effect in the FST with an increase in the dendritic complexity and the number of dendritic spines in the dentate gyrus (DG) of the hippocampus, revealed by the thin and stubby categories of neurons at the granular cell layer. At the same time, an increase of mBDNF and synaptophysin expression was observed in the hippocampus of rats that received the combination of AE-PG and CIT.
Collapse
Affiliation(s)
- Nelly-Maritza Vega-Rivera
- Laboratorio de Neuropsicofarmacología, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría “Ramón de la Fuente Muñiz”, Mexico City, Mexico
| | - María Eva González-Trujano
- Laboratorio de Neurofarmacología de Productos Naturales, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City, Mexico
| | - Alexandra Luna-Angula
- Laboratorio de Enfermedades Neuromusculares, División de Neurociencias Clínicas, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico
| | - Laura Sánchez-Chapul
- Laboratorio de Enfermedades Neuromusculares, División de Neurociencias Clínicas, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico
| | - Erika Estrada-Camarena
- Laboratorio de Neuropsicofarmacología, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría “Ramón de la Fuente Muñiz”, Mexico City, Mexico
| |
Collapse
|
45
|
Kaltsas A, Zachariou A, Markou E, Dimitriadis F, Sofikitis N, Pournaras S. Microbial Dysbiosis and Male Infertility: Understanding the Impact and Exploring Therapeutic Interventions. J Pers Med 2023; 13:1491. [PMID: 37888102 PMCID: PMC10608462 DOI: 10.3390/jpm13101491] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 10/10/2023] [Accepted: 10/12/2023] [Indexed: 10/28/2023] Open
Abstract
The human microbiota in the genital tract is pivotal for maintaining fertility, but its disruption can lead to male infertility. This study examines the relationship between microbial dysbiosis and male infertility, underscoring the promise of precision medicine in this field. Through a comprehensive review, this research indicates microbial signatures associated with male infertility, such as altered bacterial diversity, the dominance of pathogenic species, and imbalances in the genital microbiome. Key mechanisms linking microbial dysbiosis to infertility include inflammation, oxidative stress, and sperm structural deterioration. Emerging strategies like targeted antimicrobial therapies, probiotics, prebiotics, and fecal microbiota transplantation have shown potential in adjusting the genital microbiota to enhance male fertility. Notably, the application of precision medicine, which customizes treatments based on individual microbial profiles and specific causes of infertility, emerges as a promising approach to enhance treatment outcomes. Ultimately, microbial dysbiosis is intricately linked to male infertility, and embracing personalized treatment strategies rooted in precision medicine principles could be the way forward in addressing infertility associated with microbial factors.
Collapse
Affiliation(s)
- Aris Kaltsas
- Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece; (A.K.); (A.Z.); (N.S.)
| | - Athanasios Zachariou
- Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece; (A.K.); (A.Z.); (N.S.)
| | - Eleftheria Markou
- Department of Microbiology, University Hospital of Ioannina, 45500 Ioannina, Greece;
| | - Fotios Dimitriadis
- Department of Urology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Nikolaos Sofikitis
- Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece; (A.K.); (A.Z.); (N.S.)
| | - Spyridon Pournaras
- Clinical Microbiology Laboratory, Attikon General University Hospital of Athens, 12462 Athens, Greece
| |
Collapse
|
46
|
Han D, Wu Y, Lu D, Pang J, Hu J, Zhang X, Wang Z, Zhang G, Wang J. Polyphenol-rich diet mediates interplay between macrophage-neutrophil and gut microbiota to alleviate intestinal inflammation. Cell Death Dis 2023; 14:656. [PMID: 37813835 PMCID: PMC10562418 DOI: 10.1038/s41419-023-06190-4] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 09/18/2023] [Accepted: 09/28/2023] [Indexed: 10/11/2023]
Abstract
Dietary phenolic acids alleviate intestinal inflammation through altering gut microbiota composition and regulating macrophage activation. However, it is unclear how individual phenolic acids affect the interactions between intestinal microbiota and macrophages in the context of inflammatory bowel disease (IBD). Here, we aim to elucidate the mechanism by which phenolic acids alleviate gut inflammation. Mice with or without depletion of macrophages were administered with four individual phenolic acids including chlorogenic, ferulic, caffeic, and ellagic acids, following dextran sulfate sodium (DSS) treatment. Gut microbiota depletion and fecal microbiota transplantation were further performed in mice to investigate the role of the gut microbiota in phenolic acid-mediated protective effect. Colitis severity was evaluated using histological, serological, and immunological measurements. Absence of intestinal microbiota and macrophage deteriorate the epithelial injury in DSS colitis. Chlorogenic acid mitigated colitis by reducing M1 macrophage polarization through suppression of pyruvate kinase M 2 (Pkm2)-dependent glycolysis and inhibition of NOD-like receptor protein 3 (Nlrp3) activation. However, ferulic acid-mediated reduction of colitis was neutrophil-dependent through diminishing the formation of neutrophil extracellular traps. On the other hand, the beneficial effects of caffeic acid and ellagic acid were dependent upon the gut microbiota. In fact, urolithin A (UroA), a metabolite transformed from ellagic acid by the gut microbiota, was found to alleviate colitis and enhance gut barrier function in an IL22-dependent manner. Overall, our findings demonstrated that the mechanisms by which phenolic acid protected against colitis were resulted from the interaction between gut microbiota and macrophage-neutrophil.
Collapse
Affiliation(s)
- Dandan Han
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Yujun Wu
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Dongdong Lu
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Jiaman Pang
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Jie Hu
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Xiangyu Zhang
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Zhenyu Wang
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Guolong Zhang
- Department of Animal and Food Sciences, Oklahoma State University, Stillwater, OK, 74078, USA
| | - Junjun Wang
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
| |
Collapse
|
47
|
Zabolotneva AA, Gaponov AM, Roumiantsev SA, Vasiliev IY, Grigoryeva TV, Kit OI, Zlatnik EY, Maksimov AY, Goncharova AS, Novikova IA, Appolonova SA, Markin PA, Shestopalov AV. Alkylresorcinols as New Modulators of the Metabolic Activity of the Gut Microbiota. Int J Mol Sci 2023; 24:14206. [PMID: 37762509 PMCID: PMC10532030 DOI: 10.3390/ijms241814206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 09/12/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
Alkylresorcinols (ARs) are polyphenolic compounds with a wide spectrum of biological activities and are potentially involved in the regulation of host metabolism. The present study aims to establish whether ARs can be produced by the human gut microbiota and to evaluate alterations in content in stool samples as well as metabolic activity of the gut microbiota of C57BL, db/db, and LDLR (-/-) mice according to diet specifications and olivetol (5-n-pentylresorcinol) supplementation to estimate the regulatory potential of ARs. Gas chromatography with mass spectrometric detection was used to quantitatively analyse AR levels in mouse stool samples; faecal microbiota transplantation (FMT) from human donors to germ-free mice was performed to determine whether the intestinal microbiota could produce AR molecules; metagenome sequencing analysis of the mouse gut microbiota followed by reconstruction of its metabolic activity was performed to investigate olivetol's regulatory potential. A significant increase in the amounts of individual members of AR homologues in stool samples was revealed 14 days after FMT. Supplementation of 5-n-Pentylresorcinol to a regular diet influences the amounts of several ARs in the stool of C57BL/6 and LDLR (-/-) but not db/db mice, and caused a significant change in the predicted metabolic activity of the intestinal microbiota of C57BL/6 and LDLR (-/-) but not db/db mice. For the first time, we have shown that several ARs can be produced by the intestinal microbiota. Taking into account the dependence of AR levels in the gut on olivetol supplementation and microbiota metabolic activity, AR can be assumed to be potential quorum-sensing molecules, which also influence gut microbiota composition and host metabolism.
Collapse
Affiliation(s)
- Anastasia A. Zabolotneva
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, N. I. Pirogov Russian National Research Medical University, 1 Ostrovitianov Str., Moscow 117997, Russia; (S.A.R.); (A.V.S.)
- Russian National Medical Research Center for Endocrinology, 11 Dm. Ulyanova Str., Moscow 117036, Russia
| | - Andrei M. Gaponov
- Center for Digital and Translational Biomedicine «Center for Molecular Health», 32 Nakhimovskiy prospekt, Moscow 117218, Russia
| | - Sergey A. Roumiantsev
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, N. I. Pirogov Russian National Research Medical University, 1 Ostrovitianov Str., Moscow 117997, Russia; (S.A.R.); (A.V.S.)
- Russian National Medical Research Center for Endocrinology, 11 Dm. Ulyanova Str., Moscow 117036, Russia
| | - Ilya Yu. Vasiliev
- Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya Street, Kazan 420008, Russia
| | - Tatiana V. Grigoryeva
- Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya Street, Kazan 420008, Russia
| | - Oleg I. Kit
- National Medical Research Centre for Oncology, 14 Line, 63, Rostov-on-Don 344019, Russia (E.Y.Z.); (A.Y.M.); (A.S.G.); (I.A.N.)
| | - Elena Yu. Zlatnik
- National Medical Research Centre for Oncology, 14 Line, 63, Rostov-on-Don 344019, Russia (E.Y.Z.); (A.Y.M.); (A.S.G.); (I.A.N.)
| | - Aleksey Yu. Maksimov
- National Medical Research Centre for Oncology, 14 Line, 63, Rostov-on-Don 344019, Russia (E.Y.Z.); (A.Y.M.); (A.S.G.); (I.A.N.)
| | - Anna S. Goncharova
- National Medical Research Centre for Oncology, 14 Line, 63, Rostov-on-Don 344019, Russia (E.Y.Z.); (A.Y.M.); (A.S.G.); (I.A.N.)
| | - Inna A. Novikova
- National Medical Research Centre for Oncology, 14 Line, 63, Rostov-on-Don 344019, Russia (E.Y.Z.); (A.Y.M.); (A.S.G.); (I.A.N.)
| | - Svetlana A. Appolonova
- Laboratory of Pharmacokinetics and Metabolomic Analysis, Institute of Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, 2-4 Bolshaya Pirogovskaya St., Moscow 119991, Russia; (S.A.A.); (P.A.M.)
| | - Pavel A. Markin
- Laboratory of Pharmacokinetics and Metabolomic Analysis, Institute of Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, 2-4 Bolshaya Pirogovskaya St., Moscow 119991, Russia; (S.A.A.); (P.A.M.)
| | - Aleksandr V. Shestopalov
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, N. I. Pirogov Russian National Research Medical University, 1 Ostrovitianov Str., Moscow 117997, Russia; (S.A.R.); (A.V.S.)
- Russian National Medical Research Center for Endocrinology, 11 Dm. Ulyanova Str., Moscow 117036, Russia
- Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela Str., Moscow 117997, Russia
| |
Collapse
|
48
|
Satheesh Babu AK, Srinivasan H, Anandh Babu PV. Breaking bugs: gut microbes metabolize dietary components and modulate vascular health. Crit Rev Food Sci Nutr 2023; 64:12411-12419. [PMID: 37651204 PMCID: PMC10902197 DOI: 10.1080/10408398.2023.2251616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
Abstract
Gut microbiota modulates host physiology and pathophysiology through the production of microbial metabolites. Diet is a crucial factor in shaping the microbiome, and gut microbes interact with the host by producing beneficial or detrimental diet-derived microbial metabolites. Evidence from our lab and others indicates that the interaction between diet and gut microbes plays a pivotal role in modulating vascular health. Diet-derived microbial metabolites such as short-chain fatty acids and metabolites of phenolic acids improve vascular health, whereas trimethylamine oxide and certain amino acid-derived microbial metabolites impair the vasculature. These metabolites have been shown to regulate blood pressure, vascular inflammation, and atherosclerosis by acting on multiple targets. Nonetheless, there are substantial gaps in knowledge within this field. The microbial enzymes essential for the production of diet-derived metabolites, the role of the food matrix in regulating the bioavailability of metabolites, and the structure-activity relationships between metabolites and biomolecules in the vasculature are largely unknown. Potential diet-derived metabolites to improve vascular health can be identified through future studies that investigate the causal relationship between dietary components, gut microbes, diet-derived metabolites, and vascular health by using radiolabeled compounds, metabolomics, transcriptomics, and proteomics techniques.
Collapse
Affiliation(s)
| | | | - Pon Velayutham Anandh Babu
- Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, Utah 84112, USA
| |
Collapse
|
49
|
Fernández-Murga ML, Gil-Ortiz F, Serrano-García L, Llombart-Cussac A. A New Paradigm in the Relationship between Gut Microbiota and Breast Cancer: β-glucuronidase Enzyme Identified as Potential Therapeutic Target. Pathogens 2023; 12:1086. [PMID: 37764894 PMCID: PMC10535898 DOI: 10.3390/pathogens12091086] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 08/22/2023] [Accepted: 08/23/2023] [Indexed: 09/29/2023] Open
Abstract
Breast cancer (BC) is the most frequently occurring malignancy and the second cancer-specific cause of mortality in women in developed countries. Over 70% of the total number of BCs are hormone receptor-positive (HR+), and elevated levels of circulating estrogen (E) in the blood have been shown to be a major risk factor for the development of HR+ BC. This is attributable to estrogen's contribution to increased cancer cell proliferation, stimulation of angiogenesis and metastasis, and resistance to therapy. The E metabolism-gut microbiome axis is functional, with subjacent individual variations in the levels of E. It is conceivable that the estrobolome (bacterial genes whose products metabolize E) may contribute to the risk of malignant neoplasms of hormonal origin, including BC, and may serve as a potential biomarker and target. It has been suggested that β-glucuronidase (GUS) enzymes of the intestinal microbiome participate in the strobolome. In addition, it has been proposed that bacterial GUS enzymes from the gastrointestinal tract participate in hormone BC. In this review, we discuss the latest knowledge about the role of the GUS enzyme in the pathogenesis of BC, focusing on (i) the microbiome and E metabolism; (ii) diet, estrobolome, and BC development; (iii) other activities of the bacterial GUS; and (iv) the new molecular targets for BC therapeutic application.
Collapse
Affiliation(s)
- M. Leonor Fernández-Murga
- Clinical and Molecular Oncology Laboratory, Hospital Arnau de Vilanova-Liria, FISABIO, 46015 Valencia, Spain; (L.S.-G.); (A.L.-C.)
| | | | - Lucía Serrano-García
- Clinical and Molecular Oncology Laboratory, Hospital Arnau de Vilanova-Liria, FISABIO, 46015 Valencia, Spain; (L.S.-G.); (A.L.-C.)
| | - Antonio Llombart-Cussac
- Clinical and Molecular Oncology Laboratory, Hospital Arnau de Vilanova-Liria, FISABIO, 46015 Valencia, Spain; (L.S.-G.); (A.L.-C.)
| |
Collapse
|
50
|
Navalón-Monllor V, Soriano-Romaní L, Silva M, de Las Hazas MCL, Hernando-Quintana N, Suárez Diéguez T, Esteve PM, Nieto JA. Microbiota dysbiosis caused by dietetic patterns as a promoter of Alzheimer's disease through metabolic syndrome mechanisms. Food Funct 2023; 14:7317-7334. [PMID: 37470232 DOI: 10.1039/d3fo01257c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/21/2023]
Abstract
Microbiota dysbiosis and metabolic syndrome, consequences of a non-adequate diet, generate a feedback pathogenic state implicated in Alzheimer's disease development. The lower production of short chain fatty acids (SCFAs) under dysbiosis status leads to lipid homeostasis deregulation and decreases Angptl4 release and AMPK activation in the adipose tissue, promoting higher lipid storage (adipocyte hypertrophy) and cholesterol levels. Also, low SCFA generation reduces GPR41 and GPR43 receptor activation at the adipose tissue (increasing leptin release and leptin receptor resistance) and intestinal levels, reducing the release of GLP-1 and YPP. Therefore, lower satiety sensation and energy expenditure occur, promoting a weight gaining environment mediated by higher food intake and lipid storage, developing dyslipemia. In this context, higher glucose levels, together with higher free fatty acids in the bloodstream, promote glycolipotoxicity, provoking a reduction in insulin released, insulin receptor resistance, advanced glycation products (AGEs) and type 2 diabetes. Intestinal dysbiosis and low SCFAs reduce bacterial biodiversity, increasing lipopolysaccharide (LPS)-producing bacteria and intestinal barrier permeability. Higher amounts of LPS pass to the bloodstream (endotoxemia), causing a low-grade chronic inflammatory state characterized by higher levels of leptin, IL-1β, IL-6 and TNF-α, together with a reduced release of adiponectin and IL-10. At the brain and neuronal levels, the generated insulin resistance, low-grade chronic inflammation, leptin resistance, AGE production and LPS increase directly impact the secretase enzymes and tau hyperphosphorylation, creating an enabling environment for β-amyloid senile plaque and tau tangled formations and, as a consequence, Alzheimer's initiation, development and maintenance.
Collapse
Affiliation(s)
- Víctor Navalón-Monllor
- Vithas Aguas Vivas Hospital, Carretera Alzira-Tavernes de Valldigna CV-50, Km 12, 46740, Carcaixent, Valencia, Spain
| | - Laura Soriano-Romaní
- Ainia Technological Centre, Calle Benjamin Franklin 5-11, Parque Tecnológico de Valencia, E46980, 15 Paterna, Valencia, Spain.
| | - Mariana Silva
- Bioactivity and Nutritional Immunology Group (BIOINUT), Faculty of Health Science, Universidad Internacional de Valencia (VIU), Calle Pintor Sorolla 21, E46002, Valencia, Spain
| | - María-Carmen López de Las Hazas
- Laboratory of Epigenetics of Lipid Metabolism, Instituto Madrileño de Estudios Avanzados (IMDEA)-Alimentación, CEI UAM+CSIC, 28049 Madrid, Spain
| | | | - Teodoro Suárez Diéguez
- Academic Area of Nutrition, Institute of Health Sciences, Autonomous University of the State of Hidalgo, Abasolo 600, Colonia Centro, Pachuca de Soto, E42000, Hidalgo, Mexico
| | - Pere Morell Esteve
- Bioactivity and Nutritional Immunology Group (BIOINUT), Faculty of Health Science, Universidad Internacional de Valencia (VIU), Calle Pintor Sorolla 21, E46002, Valencia, Spain
| | - Juan Antonio Nieto
- Ainia Technological Centre, Calle Benjamin Franklin 5-11, Parque Tecnológico de Valencia, E46980, 15 Paterna, Valencia, Spain.
- Bioactivity and Nutritional Immunology Group (BIOINUT), Faculty of Health Science, Universidad Internacional de Valencia (VIU), Calle Pintor Sorolla 21, E46002, Valencia, Spain
| |
Collapse
|