Gut Antioxidants
SCIENTIFIC RESEARCH ON THE FOLLOWING INGREDIENTS:
Tribulus terrestris
Antibacterial and antifungal activities of different parts of Tribulus terrestris L. growing in Iraq
Abstract
Antimicrobial activity of organic and aqueous extracts from fruits, leaves and roots of Tribulus terrestris L., an Iraqi medicinal plant used as urinary anti-infective in folk medicine, was examined against 11 species of pathogenic and non-pathogenic microorganisms: Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Corynebacterium diphtheriae, Escherichia coli, Proteus vulgaris, Serratia marcescens, Salmonella typhimurium, Klebsiella pneumoniae, Pseudomonas aeruginosa and Candida albicans using microdilution method in 96 multiwell microtiter plates. All the extracts from the different parts of the plant showed antimicrobial activity against most tested microorganisms. The most active extract against both Gram-negative and Gram-positive bacteria was ethanol extract from the fruits with a minimal inhibitory concentration (MIC) value of 0.15 mg/ml against B. subtilis, B. cereus, P. vulgaris and C. diphtheriae. In addition, the same extract from the same plant part demonstrated the strongest antifungal activity against C. albicans with an MIC value of 0.15 mg/ml.
Source: Firas A. Al-Bayati and Hassan F. Al-Mola. “Antibacterial and antifungal activities of different parts of Tribulus terrestris L. growing in Iraq” Journal of Zhejiang University Science B (2008): 9(2): 154–159.
Ginger (Zingiber officinale)
Gut Microbiota Variation with Short-Term Intake of Ginger Juice on Human Health
Abstract
Ginger, a widely used functional food and food additive, little is known about the effect of ginger juice, which is rich in many healthful agents, on healthy humans or on its relationship with gut microbiota composition variation. The aim of this study was to investigate the changes in the gut microbial communities that occur following the supplementation of fresh ginger-derived juice in healthy adults and its potential associations with function. A crossover intervention study in which 123 healthy subjects (63 men and 60 women) consumed fresh ginger juice from Zingiber officinale Rosc. or sterile 0.9% sodium chloride was conducted. 16S rRNA sequencing analyses were applied to characterize gut microbiota variation. We found that ginger juice intervention increased the species number of intestinal flora. A decreased relative abundance of the Prevotella-to-Bacteroides ratio and pro-inflammatory Ruminococcus_1 and Ruminococcus_2 while a tendency toward an increased Firmicutes-to-Bacteroidetes ratio, Proteobacteria and anti-inflammatory Faecalibacterium were found. When we did not consider gender, we found differences in bacterial diversity both in community evenness and in richness caused by ginger intervention. In fact, there were different changes in bacterial α-diversity induced by the ginger juice in men and women. We identified 19 bacterial genera with significant differences between the control group (women) and ginger group (women) and 15 significant differences between the control group (men) and ginger group (men) at the genus level. Our results showed that short-term intake of ginger juice had substantial effects on the composition and function of gut microbiota in healthy people. Moreover, our findings underscored the importance of analyzing both male and female individuals to investigate the effects of ginger on gut microbiota. Additional studies are necessary to confirm these findings.
Overall, ginger consumption appeared to have the potential to manage obesity. Wang et al. (2019) found ginger powder had beneficial effects on the prevention of obesity through modulation of gut microbiota in mice. The abundance of Proteobacteria in the normal chow diet-fed mice was notably higher after ginger supplementation, which was in agreement with our results. In their research, however, no significant changes were found in the level of the Firmicutes-to-Bacteroidetes ratio, possibly because of the intrinsic similarities and differences that exist between the human and murine core gut microbiota (Nguyen et al., 2015). Specifically, ginger juice interventions increased the Firmicutes-to-Bacteroidetes ratio, which also has been observed in populations with short-term dietary capsaicin or whole-grain intervention and in healthy subjects after the long-term consumption of vegetables, dietary fibers, and whole grain (Wu et al., 2011; Kang et al., 2016).
The gut microbiota composition and dysbiosis influence on the hormone orchestration indirectly affected appetite (Mitev and Taleski, 2019). Leptin is a hormone produced mainly by adipose tissue that inhibits appetite and fat synthesis and increases energy consumption to control body weight when present at higher levels. It has been suggested that a significant negative correlation exists between the plasmatic levels of leptin and the genus Prevotella (Mitev and Taleski, 2019; Pushpanathan et al., 2019). In this study, we found that the ginger group presented a lower Prevotella genus level (6.22%) compared with the control group (12.5%) at time point T7 (Supplementary Table S1). Moreover, although the ginger group presented a higher Bacteroidetes genus level (13.93%) compared with the control group (12.66%), ginger juice interventions decreased the Prevotella-to-Bacteroides ratio. Another study showed that the Prevotella-to-Bacteroides ratio was positively correlated with the total plasma cholesterol levels (Roager et al., 2014).
In addition, we found that pro-inflammatory (Hall et al., 2017) Ruminococcus_1 went from 1.5% of total microbial abundance to 0.9%, the abundance of genus Ruminococcus_2 decreased from 2.1 to 1.79%, and the anti-inflammatory butyrate producer (Hills et al., 2019) Faecalibacterium experienced an expansion of 5.85–7.79% microbial abundance (Supplementary Table S1). It has been reported that a decrease in Ruminococcus, a member of the Clostridia class responsible for degrading resistant starch, also closed relative to an increase in butyrate production (Valles-Colomer et al., 2019). These results indicated that the anti-inflammatory effects of ginger may be at least partially due to variations in the relative abundance of these butyrate-related species. Collectively, these results showed that short-term intake of ginger juice had substantial effects on the composition and function of gut microbiota in healthy people.
Source: Xiaolong Wang, Dan Zhang Haiqiang Jiang, Shuo Zhang, Xiaogang Pang, Shijie Gao, Huimin Zhang, Shanyu Zhang, Qiuyue Xiao,Liyuan Chen, Shengqi Wang, Dongmei Qi, and Yunlun Li. “Gut Microbiota Variation With Short-Term Intake of Ginger Juice on Human Health” Frontiers in Microbiology (2021) doi.org/10.3389/fmicb.2020.576061
Quercetin
Dietary Quercetin Supplementation Attenuates Diarrhea and Intestinal Damage by Regulating Gut Microbiota in Weanling Piglets
Abstract
Antioxidant polyphenols from plants are potential dietary supplementation to alleviate early weaning-induced intestinal disorders in piglets. Recent evidences showed polyphenol quercetin could reshape gut microbiota when it functioned as anti-inflammation or antioxidation agents in rodent models. However, the effect of dietary quercetin supplementation on intestinal disorders and gut microbiota of weanling piglets, along with the role of gut microbiota in this effect, both remain unclear. Here, we determined the quercetin's effect on attenuating diarrhea, intestinal damage, and redox imbalance, as well as the role of gut microbiota by transferring the quercetin-treated fecal microbiota to the recipient piglets. The results showed that dietary quercetin supplementation decreased piglets' fecal scores improved intestinal damage by increasing tight junction protein occludin, villus height, and villus height/crypt depth ratio but decreased crypt depth and intestinal epithelial apoptosis (TUNEL staining). Quercetin also increased antioxidant capacity indices, including total antioxidant capacity, catalase, and glutathione/oxidized glutathione disulfide but decreased oxidative metabolite malondialdehyde in the jejunum tissue. Fecal microbiota transplantation (FMT) from quercetin-treated piglets had comparable effects on improving intestinal damage and antioxidative capacity than dietary quercetin supplementation. Further analysis of gut microbiota using 16S rDNA sequencing showed that dietary quercetin supplementation or FMT shifted the structure and increased the diversity of gut microbiota. Especially, anaerobic trait and carbohydrate metabolism functions of gut microbiota were enriched after dietary quercetin supplementation and FMT, which may owe to the increased antioxidative capacity of intestine. Quercetin increased the relative abundances of Fibrobacteres, Akkermansia muciniphila, Clostridium butyricum, Clostridium celatum, and Prevotella copri but decreased the relative abundances of Proteobacteria, Lactobacillus coleohominis, and Ruminococcus bromii. Besides, quercetin-shifted bacteria and carbohydrate metabolites short chain fatty acids were significantly related to the indices of antioxidant capacity and intestinal integrity. Overall, dietary quercetin supplementation attenuated diarrhea and intestinal damage by enhancing the antioxidant capacity and regulating gut microbial structure and metabolism in piglets.
Source: Baoyang Xu, Wenxia Qin, Yunzheng Xu, Wenbo Yang, Yuwen Chen, Juncheng Huang, Jianan Zhao, and Libao Ma. “Dietary Quercetin Supplementation Attenuates Diarrhea and Intestinal Damage by Regulating Gut Microbiota in Weanling Piglets” Oxidative Medicine and Cellular Longevity (2021) 6221012.
Berberine HCl (Berberis artistata)
Effects of Berberine on the Gastrointestinal Microbiota
Abstract
The gastrointestinal microbiota is a multi-faceted system that is unraveling novel contributors to the development and progression of several diseases. Berberine has been used to treat obesity, diabetes mellitus, atherosclerosis, and metabolic diseases in China. There are also clinical trials regarding berberine use in cardiovascular, gastrointestinal, and endocrine diseases. Berberine elicits clinical benefits at standard doses and has low toxicity. The mechanism underlying the role of berberine in lipid‐lowering and insulin resistance is incompletely understood, but one of the possible mechanisms is related to its effect on the gastrointestinal microbiota. An extensive search in electronic databases (PubMed, Scopus, Embase, Web of Sciences, Science Direct) was used to identify the role of the gastrointestinal microbiota in the berberine treatment. The aim of this review was to summarize the pharmacologic effects of berberine on animals and humans by regulation of the gastrointestinal microbiota.
The Effects of Berberine on the GM: The GM is also known to affect drug metabolism, both directly and indirectly, and particularly with regards to drugs that are administered orally. Berberine reduces the levels of lipids and glucose in the blood via multi-target mechanisms, including modulation of the GM composition (Zhang et al., 2012). Berberine is also known to reduce the diversity of the GM and interfere with the relative abundance of Desulfovibrio, Eubacterium, and Bacteroides (Cui et al., 2018b). In addition, Bacteroides were shown to be enriched in the colon and terminal ileum of mice (C57BL/6) treated with berberine, but berberine treatment reduced the populations of Ruminococcus gnavu (Genus of Mediterraneibacter), Ruminococcus schinkii (Genus of Blautia), Lactobacillus acidophilus (Genus of Lactobacillus), Lactobacillus murinus (Genus of Ligilactobacillus), and Lactococcus lactis (Genus of Lactococcus) (Guo et al., 2016). Recent studies have shown that berberine has beneficial effects on the immune cells of the intestinal immune system and affects the expression of several intestinal immune factors. Berberine has also been shown to inhibit the mRNA expression of interleukin (IL)-1β, IL-4, IL-10, macrophage migration inhibitory factor (MIF), and tumor necrosis factor (TNF)-α, while also reducing low-grade inflammation (Gong et al., 2017). Short-term exposure to berberine alters the populations of intestinal bacteria by reducing the activity of Clostridium cluster XIVa and IV, and their bile salt hydrolase (BSH), thus leading to the accumulation of taurocholic acid (TCA). TCA can activate intestinal farnesoid X receptor (FXR) which can then mediate the metabolism of bile acids, lipids, and glucose (Tian et al., 2019). Butyrate is a short-chain fatty acid (SCFA) produced during fermentation of fibers and other substrates by an anaerobic bacteria resident in the gastrointestinal tract (Roediger et al., 1982). Berberine has also been shown to enrich the population of butyrate-producing bacteria in the GM, thus promoting the synthesis of butyrate via the acetyl CoA-butyryl CoA-butyrate pathway. Subsequently, the butyrate enters the blood and reduces the levels of lipids and glucose (Wang et al., 2017b).
The GM is known to play a key role in the development of metabolic disorders. One factor underlying the application of berberine treatment is that berberine can increase the rates of cellular glucose uptake and metabolism (Cok et al., 2011). Other research studies are investigating the effects of berberine against cancer. In this article, we review the role of the GM on non-transmissible diseases following berberine treatment.
The Effects of Berberine on Other Diseases: The modulation of berberine-induced GM plays a significant role in the development of IBD and atherosclerosis (Cui et al., 2018). IBD is caused by dysregulation of the immune responses in the intestinal mucosal in hosts that are genetically susceptible (Strober et al., 2007). Berberine has also been shown to inhibit the production of pro-inflammatory cytokines in colonic macrophages and epithelial cells, and promote apoptosis in the colon macrophages of mice (C57BL/6) treated with DSS. Berberine was also shown to reduce the activation of the signaling pathways that produce proinflammatory cytokines (including mitogen-activated protein kinase and NF-κB) in colonic macrophages and epithelial cells in DSS-treated mice (Yan et al., 2012). In the intestinal mucositis induced by 5-fluorouracil (5-Fu) using rat model, berberine significantly increased the levels of butyrate and glutamine in feces from 5-Fu treated rats. In terms of gut microbiota, berberine enriched the relative abundance of Firmicutes and decreased Proteobacteria at the phylum level. Meanwhile, berberine increased the proportion of unclassified_f_ Porphyromonadaceae, unclassified_f_ Lachnospiraceae, Lactobacillus, unclassified_o_Clostridiales, Ruminococcus, Prevotella, Clostridium IV, and decreased Escherichia/Shigella at the genera level (Chen et al., 2020).
Clinical evidence suggests that berberine can reduce endothelial inflammation and improve vascular health (Cicero and Baggioni, 2016). Shi et al. further reported that berberine may modulate the composition of the GM in subjects with atherosclerosis (Shi et al., 2018). Other studies have shown that berberine could be used to treat atherosclerosis by increasing the abundance of Akkermansia spp in mice (C57BL) fed a high-fat diet (Zhu et al., 2018). In addition, berberine was shown to reduce HFD-induced metabolic endotoxemia and the expression of proinflammatory cytokines and chemokines in the arteries and in the intestine.
Other research has shown that berberine can reduce the expression of hepatic flavin-containing monooxygenase 3 (FMO3) and the serum levels of proteins involved in the trimethylamine N-oxide FXR signaling pathway (Shi et al., 2018). Similarly, the levels of primary bile acids (e.g., β-muricholic acid and tauroursodeoxycholic acid) were shown to be increased in the livers and sera of mice (C57BL/6) fed berberine; the levels of secondary bile acids (lithocholic acid and T-conjugates) were reduced (Guo et al., 2016). Another study reported that the expression of bile acid-synthetic enzymes (e.g., cytochrome P450 (Cyp)7a1 and Cyp8b1), and an uptake transporter sodium taurocholate co-transporting polypeptide (Ntcp), increased by 39 to 400% in the livers of mice fed high doses of berberine; however, there was no significant change in the expression levels of the nuclear receptor and efflux transporter (Guo et al., 2016).
Berberine treatment has also been shown to increase the abundance of Akkermansia in the intestine and alleviate atherosclerosis in Apoe (-/-) mice fed a high-fat diet (Zhu et al., 2018). Collectively, these data indicate that berberine may play different regulatory roles in different disease models and that berberine acts via many different systems on a range of targets in the treatment of disease.
Source: Lichao Zhang, Xiaoying Wu, Ruibing Yang, Fang Chen, Yao Liao, Zifeng Zhu, Zhongdao Wu, Xi Sun, and Lifu Wang. “Effects of Berberine on the Gastrointestinal Microbiota” Frontiers in Cellular and Infection Microbiology (2020): 10: 588517.
Cocoa
Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study
Abstract
Background: The absorption of cocoa flavanols in the small intestine is limited, and the majority of the flavanols reach the large intestine where they may be metabolized by resident microbiota.
Objective: We assessed the prebiotic potential of cocoa flavanols in a randomized, double-blind, crossover, controlled intervention study.
Design: Twenty-two healthy human volunteers were randomly assigned to either a high-cocoa flavanol (HCF) group (494 mg cocoa flavanols/d) or a low-cocoa flavanol (LCF) group (23 mg cocoa flavanols/d) for 4 wk. This was followed by a 4-wk washout period before volunteers crossed to the alternant arm. Fecal samples were recovered before and after each intervention, and bacterial numbers were measured by fluorescence in situ hybridization. A number of other biochemical and physiologic markers were measured.
Results: Compared with the consumption of the LCF drink, the daily consumption of the HCF drink for 4 wk significantly increased the bifidobacterial (P < 0.01) and lactobacilli (P < 0.001) populations but significantly decreased clostridia counts (P < 0.001). These microbial changes were paralleled by significant reductions in plasma triacylglycerol (P < 0.05) and C-reactive protein (P < 0.05) concentrations. Furthermore, changes in C-reactive protein concentrations were linked to changes in lactobacilli counts (P < 0.05, R(2)=-0.33 for the model). These in vivo changes were closely paralleled by cocoa flavanol-induced bacterial changes in mixed-batch culture experiments.
Conclusion: This study shows, for the first time to our knowledge, that consumption of cocoa flavanols can significantly affect the growth of select gut microflora in humans, which suggests the potential prebiotic benefits associated with the dietary inclusion of flavanol-rich foods. This trial was registered at clinicaltrials.gov as NCT01091922.
Source: Xenofon Tzounis, Ana Rodriguez-Mateos, Jelena Vulevic, Glenn R. Gibson, Catherine Kwik-Uribe, and Jeremy P. E. Spencer. “Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study” The American Journal of Clinical Nutrition (2011): 93(1):62-72.