Potential Implications of Citrulline and Quercetin on Gut Functioning of Monogastric Animals and Humans: A Comprehensive Review

The importance of gut health in animal welfare and wellbeing is undisputable. The intestinal microbiota plays an essential role in the metabolic, nutritional, physiological, and immunological processes of animals. Therefore, the rapid development of dietary supplements to improve gut functions and homeostasis is imminent. Recent studies have uncovered the beneficial effects of dietary supplements on the immune response, microbiota, gut homeostasis, and intestinal health. The application of citrulline (a functional gut biomarker) and quercetin (a known potent flavonoid) to promote gut functions has gained considerable interest as both bioactive substances possess anti-inflammatory, anti-oxidative, and immunomodulatory properties. Research has demonstrated that both citrulline and quercetin can mediate gut activities by combating disruptions to the intestinal integrity and alterations to the gut microbiota. In addition, citrulline and quercetin play crucial roles in maintaining intestinal immune tolerance and gut health. However, the synergistic benefits which these dietary supplements (citrulline and quercetin) may afford to simultaneously promote gut functions remain to be explored. Therefore, this review summarizes the modulatory effects of citrulline and quercetin on the intestinal integrity and gut microbiota, and further expounds on their potential synergistic roles to attenuate intestinal inflammation and promote gut health.

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Dietary resveratrol attenuation of intestinal inflammation and oxidative damage is linked to the alteration of gut microbiota and butyrate in piglets challenged with deoxynivalenol

Journal of Animal Science and Biotechnology ◽

10.1186/s40104-021-00596-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yueqin Qiu ◽

Jun Yang ◽

Li Wang ◽

Xuefen Yang ◽

Kaiguo Gao ◽

...

Keyword(s):

Gut Microbiota ◽

Oxidative Damage ◽

Protein Expression ◽

Intestinal Inflammation ◽

Control Diet ◽

Intestinal Barrier Function ◽

Protective Effects ◽

Gut Health ◽

Antioxidant Genes ◽

Mrna And Protein Expression

Abstract Background Deoxynivalenol (DON) is a widespread mycotoxin that induces intestinal inflammation and oxidative stress in humans and animals. Resveratrol (RES) effectively exerts anti-inflammatory and antioxidant effects. However, the protective effects of RES on alleviating DON toxicity in piglets and the underlying mechanism remain unclear. Therefore, this study aimed to investigate the effect of RES on growth performance, gut health and the gut microbiota in DON-challenged piglets. A total of 64 weaned piglets [Duroc × (Landrace × Yorkshire), 21-d-old, 6.97 ± 0.10 kg body weight (BW)] were randomly allocated to 4 treatment groups (8 replicate pens per treatment, each pen containing 2 males; n = 16 per treatment) for 28 d. The piglets were fed a control diet (CON) or the CON diet supplemented with 300 mg RES/kg diet (RES group), 3.8 mg DON/kg diet (DON) or both (DON+RES) in a 2 × 2 factorial design. Results DON-challenged piglets fed the RES-supplemented diet had significantly decreased D-lactate concentrations and tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) mRNA and protein expression, and increased zonula occludens-1 (ZO-1) mRNA and protein expression compared with those of DON-challenged piglets fed the unsupplemented diet (P < 0.05). Compared with unsupplemented DON-challenged piglets, infected piglets fed a diet with RES showed significantly decreased malondialdehyde (MDA) levelsand increased mRNA expression of antioxidant enzymes and antioxidant genes (i.e., GCLC, GCLM, HO-1, SOD1 and NQO-1) and glutamate-cysteine-ligase modulatory subunit (GCLM) protein expression (P < 0.05). Moreover, RES supplementation significantly abrogated the increase in the proportion of TUNEL-positive cells and the protein expression of caspase3 in DON-challenged piglets (P < 0.05). Finally, RES supplementation significantly increased the abundance of Roseburia and butyrate concentrations, while decreasing the abundances of Bacteroides and unidentified-Enterobacteriaceae in DON-challenged piglets compared with DON-challenged piglets alone (P < 0.05). Conclusions RES supplementation improved gut health in DON-challenged piglets by strengthening intestinal barrier function, alleviating intestinal inflammation and oxidative damage, and positively modulating the gut microbiota. The protective effects of RES on gut health may be linked to increased Roseburia and butyrate concentrations, and decreased levels of Bacteroides and unidentified-Enterobacteriaceae.

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Could the beneficial effects of dietary calcium on obesity and diabetes control be mediated by changes in intestinal microbiota and integrity?

British Journal Of Nutrition ◽

10.1017/s0007114515003608 ◽

2015 ◽

Vol 114 (11) ◽

pp. 1756-1765 ◽

Cited By ~ 23

Author(s):

J. M. G. Gomes ◽

J. A. Costa ◽

R. C. Alfenas

Keyword(s):

Gut Microbiota ◽

Metabolic Diseases ◽

Beneficial Effects ◽

Body Weight Reduction ◽

Intestinal Integrity ◽

Obesity And Diabetes ◽

Supplementation Period ◽

Inflammatory State ◽

The Impact

AbstractEvidence from animal and human studies has associated gut microbiota, increased translocation of lipopolysaccharide (LPS) and reduced intestinal integrity (II) with the inflammatory state that occurs in obesity and type 2 diabetes mellitus (T2DM). Consumption of Ca may favour body weight reduction and glycaemic control, but its influence on II and gut microbiota is not well understood. Considering the impact of metabolic diseases on public health and the role of Ca on the pathophysiology of these diseases, this review critically discusses possible mechanisms by which high-Ca diets could affect gut microbiota and II. Published studies from 1993 to 2015 about this topic were searched and selected from Medline/PubMed, Scielo and Lilacs databases. High-Ca diets seem to favour the growth of lactobacilli, maintain II (especially in the colon), reduce translocation of LPS and regulate tight-junction gene expression. We conclude that dietary Ca might interfere with gut microbiota and II modulations and it can partly explain the effect of Ca on obesity and T2DM control. However, further research is required to define the supplementation period, the dose and the type of Ca supplement (milk or salt) required for more effective results. As Ca interacts with other components of the diet, these interactions must also be considered in future studies. We believe that more complex mechanisms involving extraintestinal disorders (hormones, cytokines and other biomarkers) also need to be studied.

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Fecal transplant from resveratrol-fed donors improves glycaemia and cardiovascular features of the metabolic syndrome in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00471.2017 ◽

2018 ◽

Vol 315 (4) ◽

pp. E511-E519 ◽

Cited By ~ 21

Author(s):

Ty T. Kim ◽

Nirmal Parajuli ◽

Miranda M. Sung ◽

Suresh C. Bairwa ◽

Jody Levasseur ◽

...

Keyword(s):

Metabolic Syndrome ◽

Gut Microbiota ◽

Glucose Homeostasis ◽

Intestinal Inflammation ◽

Obese Mice ◽

Fecal Transplant ◽

Fecal Microbiome ◽

Oral Supplementation ◽

Beneficial Effects ◽

The Metabolic Syndrome

Oral administration of resveratrol attenuates several symptoms associated with the metabolic syndrome, such as impaired glucose homeostasis and hypertension. Recent work has shown that resveratrol can improve glucose homeostasis in obesity via changes in the gut microbiota. Studies involving fecal microbiome transplants (FMTs) suggest that either live gut microbiota or bacterial-derived metabolites from resveratrol ingestion are responsible for producing the observed benefits in recipients. Herein, we show that obese mice receiving FMTs from healthy resveratrol-fed mice have improved glucose homeostasis within 11 days of the first transplant, and that resveratrol-FMTs is more efficacious than oral supplementation of resveratrol for the same duration. The effects of FMTs from resveratrol-fed mice are also associated with decreased inflammation in the colon of obese recipient mice. Furthermore, we show that sterile fecal filtrates from resveratrol-fed mice are sufficient to improve glucose homeostasis in obese mice, demonstrating that nonliving bacterial, metabolites, or other components within the feces of resveratrol-fed mice are sufficient to reduce intestinal inflammation. These postbiotics may be an integral mechanism by which resveratrol improves hyperglycemia in obesity. Resveratrol-FMTs also reduced the systolic blood pressure of hypertensive mice within 2 wk of the first transplant, indicating that the beneficial effects of resveratrol-FMTs may also assist with improving cardiovascular conditions associated with the metabolic syndrome.

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Butyric and Citric Acids and Their Salts in Poultry Nutrition: Effects on Gut Health and Intestinal Microbiota

International Journal of Molecular Sciences ◽

10.3390/ijms221910392 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10392

Author(s):

Mebratu Melaku ◽

Ruqing Zhong ◽

Hui Han ◽

Fan Wan ◽

Bao Yi ◽

...

Keyword(s):

Gut Microbiota ◽

Organic Acids ◽

Growth Performance ◽

Pathogenic Bacteria ◽

Intestinal Inflammation ◽

Farm Animals ◽

Gut Health ◽

Intestinal Health ◽

Poultry Products ◽

Poultry Nutrition

Intestinal dysfunction of farm animals, such as intestinal inflammation and altered gut microbiota, is the critical problem affecting animal welfare, performance and farm profitability. China has prohibited the use of antibiotics to improve feed efficiency and growth performance for farm animals, including poultry, in 2020. With the advantages of maintaining gut homeostasis, enhancing digestion, and absorption and modulating gut microbiota, organic acids are regarded as promising antibiotic alternatives. Butyric and citric acids as presentative organic acids positively impact growth performance, welfare, and intestinal health of livestock mainly by reducing pathogenic bacteria and maintaining the gastrointestinal tract (GIT) pH. This review summarizes the discovery of butyric acid (BA), citric acid (CA) and their salt forms, molecular structure and properties, metabolism, biological functions and their applications in poultry nutrition. The research findings about BA, CA and their salts on rats, pigs and humans are also briefly reviewed. Therefore, this review will fill the knowledge gaps of the scientific community and may be of great interest for poultry nutritionists, researchers and feed manufacturers about these two weak organic acids and their effects on intestinal health and gut microbiota community, with the hope of providing safe, healthy and nutrient-rich poultry products to consumers.

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Optimization extraction and characterization of Artemisia ordosica polysaccharide and its beneficial effects on antioxidant function and gut microbiota in rats

RSC Advances ◽

10.1039/d0ra05063f ◽

2020 ◽

Vol 10 (44) ◽

pp. 26151-26164

Author(s):

Y. Y. Xing ◽

Y. Q. Xu ◽

X. Jin ◽

L. L. Shi ◽

S. W. Guo ◽

...

Keyword(s):

Gut Microbiota ◽

Health Improvement ◽

Antioxidant Ability ◽

Gut Health ◽

Artemisia Ordosica ◽

Functional Ingredient ◽

Beneficial Effects ◽

Antioxidant Function

Artemisia ordosica polysaccharide is expected to be functional ingredient for health improvement through improving antioxidant ability and modulating gut health.

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Intermittent fasting - a potential approach to modulate the gut microbiota in humans? A systematic review

Nutrition and Healthy Aging ◽

10.3233/nha-200098 ◽

2021 ◽

pp. 1-8

Author(s):

Kate Llewellyn-Waters ◽

Mohammad M. Abdullah

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Gut Microbiota ◽

Dietary Habits ◽

Intermittent Fasting ◽

Gut Health ◽

Medline Search ◽

Beneficial Effects ◽

The Rich ◽

The Impact

Research on gut microbiota has increased in popularity over the past decade, with evidence associating different dietary habits with changes in the makeup of the rich ecosystem of microorganisms that performs a variety of functions and induces a range of health effects, within and well beyond the gastrointestinal tract. Similarly, intermittent fasting (IF), an umbrella term describing various regimens of periods of voluntary abstinence from food and drink, has classically been associated with favourable impacts on cardiovascular risk factors, body weight, circadian biology, and, more recently, the gut health..The objective of this PRISMA systematic review was to summarize the peer-reviewed literature of clinical trials related to the impact of IF regimens on the gut microbiota. A MEDLINE search was conducted using PubMed and the keywords “intermittent fasting”, “gut microbiota”, “microbes”, and others. Whilst the field is still in its infancy, an emerging body of evidence suggests beneficial effects of IF on the health of the gut through increasing the microbial diversity and abundance, with possible clinical implications related to improving the immune function and ameliorating the metabolic status. Further research in larger clinical trials is warranted before practical recommendations for the public health can be made.

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Astaxanthin n-Octanoic Acid Diester Ameliorates Insulin Resistance and Modulates Gut Microbiota in High-Fat and High-Sucrose Diet-Fed Mice

International Journal of Molecular Sciences ◽

10.3390/ijms21062149 ◽

2020 ◽

Vol 21 (6) ◽

pp. 2149 ◽

Cited By ~ 3

Author(s):

Yuan Gao ◽

Lu Yang ◽

Yaoxian Chin ◽

Fang Liu ◽

Robert W. Li ◽

...

Keyword(s):

Insulin Resistance ◽

Gut Microbiota ◽

Octanoic Acid ◽

Intestinal Inflammation ◽

Control Diet ◽

High Fat ◽

Intestinal Integrity ◽

Sucrose Diet ◽

High Sucrose Diet ◽

High Sucrose

Astaxanthin n-octanoic acid diester (AOD) is a type of astaxanthin connecting medium-chain fatty acids with a more stable structure. In this study, we examined the role of AOD in ameliorating insulin resistance (IR) induced by a high-fat and high-sucrose diet (HFD) as well as its effect on modulating gut microbiota in mice, with free astaxanthin (AST) as a comparison. Four groups of male C57BL/6J mice (6 weeks old; n = 10 per group) were fed with a normal control diet (NC), HFD orally administered with AOD, AST (50 mg/kg body weight), or vehicle for 8 weeks. AOD improved glucose tolerance, IR, systematic and intestinal inflammation, and intestinal integrity better than AST. Further, both AOD and AST modulated gut microbiota. A significantly higher abundance of Bacteroides and Coprococcus was found in AOD than in AST, and the predicted pathway of carbohydrate metabolism was significantly impacted by AOD. Overall, AOD may play a role in alleviating IR and inflammation with the modulating effect on microbiota in HFD-fed mice. Our findings could facilitate the development of AOD as a bioactive nutraceutical and more stable alternative to AST.

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Dietary Bioactive Peptide Alanyl-Glutamine Attenuates Dextran Sodium Sulfate-Induced Colitis by Modulating Gut Microbiota

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5543003 ◽

2021 ◽

Vol 2021 ◽

pp. 1-17

Author(s):

Qingbiao Xu ◽

Mingyang Hu ◽

Min Li ◽

Jinxiu Hou ◽

Xianghua Zhang ◽

...

Keyword(s):

Gut Microbiota ◽

Activity Index ◽

Intestinal Barrier ◽

Body Weight Loss ◽

Community Diversity ◽

Peptide Transporter ◽

Protective Effects ◽

Gut Health ◽

Beneficial Effects ◽

Rdna Sequencing

Inflammatory bowel disease (IBD) is a chronic intestinal disorder threatening human health. Di-peptide alanyl-glutamine (Ala-Gln) has various beneficial effects on gut health. However, its role and functional mechanism in treating IBD are still not clear. Therefore, the protective effects of Ala-Gln and glutamine (Gln) on dextran sulfate sodium- (DSS-) induced colitic mice were investigated in this study. The results showed that oral supplementation of Ala-Gln or Gln significantly attenuated the colitis symptoms in mice, including body weight loss, colon length, disease activity index, histological scores, and tissue apoptosis. The concentrations of interleukin- (IL-) 1β, IL-6, tumor necrosis factor-α, and myeloperoxidase were significantly decreased, while the concentrations of immunoglobulins (IgA, IgG, and IgM) and superoxide dismutase were significantly increased by Ala-Gln or Gln supplementation. The expression of occludin and peptide transporter 1 (PepT1) was significantly increased by Ala-Gln or Gln. Interestingly, Ala-Gln had better beneficial effects than Gln in alleviating colitis. In addition, 16S rDNA sequencing showed that the DSS-induced shifts of the microbiome (community diversity, evenness, richness, and composition) in the mouse colon were restored by Gln and Ala-Gln, including Lactobacillus, Bacteroides_acidifaciens, Bacteroidales, Firmicutes, Clostridia, Helicobacter, and Bacteroides. Correspondingly, the functions of the microflora metabolism pathways were also rescued by Ala-Gln, including fatty acid metabolism, membrane transporters, infectious diseases, and immune system. In conclusion, the results revealed that Ala-Gln can prevent colitis through PepT1, enhancing the intestinal barrier and modulating gut microbiota and microflora metabolites.

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Dietary Taxifolin Protects Against Dextran Sulfate Sodium-Induced Colitis via NF-κB Signaling, Enhancing Intestinal Barrier and Modulating Gut Microbiota

Frontiers in Immunology ◽

10.3389/fimmu.2020.631809 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jinxiu Hou ◽

Mingyang Hu ◽

Le Zhang ◽

Ya Gao ◽

Libao Ma ◽

...

Keyword(s):

Gut Microbiota ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Immunoglobulin A ◽

Intestinal Barrier ◽

Mapk Signaling ◽

Protective Effects ◽

Gut Health ◽

Beneficial Effects ◽

Rdna Sequencing

Taxifolin is a natural antioxidant polyphenol with various bioactivities and has many beneficial effects on human gut health. However, little is known of its function on colitis. In this study, the protective effects of taxifolin on colitis symptoms, inflammation, signaling pathways, and colon microbiota were investigated using dextran sulfate sodium (DSS)-induced colitis mice. Intriguingly, pre-administration of taxifolin alleviated the colitis symptoms and histological changes of the DSS-challenged mice. Supplementation of taxifolin significantly inhibited the secretions of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 and significantly increased the secretions of IL-10, secretory immunoglobulin A, superoxide dismutase, and immunoglobulins (IgA, IgG, and IgM) in DSS-induced colitis mice. In addition, the activation of nuclear factor kappa B (NF-κB; p65 and IκBα) signaling was significantly suppressed by taxifolin supplementation. The expression of tight junction proteins (claudin-1 and occludin) was significantly increased by taxifolin. Moreover, 16S rDNA sequencing revealed that the DSS-induced changes of colon microbiota composition and microbial functions (amino acid metabolism and MAPK signaling) were restored by taxifolin, including the decreases of the abundances of Bacteroides, Clostridium ramosum, Clostridium saccharogumia, Sphingobacterium multivorum, and the ratio of Bacteroidetes/Firmicutes, and the increases of the abundances of Desulfovibrio C21 c20 and Gemmiger formicilis at species level. In conclusion, these results revealed that dietary taxifolin has a great potential to prevent colitis by inhibiting the NF-κB signaling pathway, enhancing intestinal barrier, and modulating gut microbiota.

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Metabolic Responses to Butyrate Supplementation in LF- and HF-Fed Mice Are Cohort-Dependent and Associated with Changes in Composition and Function of the Gut Microbiota

Nutrients ◽

10.3390/nu12113524 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3524

Author(s):

Sunhye Lee ◽

Trina A. Knotts ◽

Michael L. Goodson ◽

Mariana Barboza ◽

Elyse Wudeck ◽

...

Keyword(s):

Body Weight ◽

Gut Microbiota ◽

Feeding Behavior ◽

Intestinal Permeability ◽

Intestinal Inflammation ◽

Metabolic Phenotype ◽

Metabolic Responses ◽

Intestinal Barrier Function ◽

Fecal Microbiome ◽

Beneficial Effects

The gut microbiota and associated metabolites have emerged as potential modulators of pathophysiological changes in obesity and related metabolic disorders. Butyrate, a product of bacterial fermentation, has been shown to have beneficial effects in obesity and rodent models of diet-induced obesity. Here, we aimed to determine the beneficial effects of butyrate (as glycerol ester of butyrate monobutyrin, MB) supplementation on metabolic phenotype, intestinal permeability and inflammation, feeding behavior, and the gut microbiota in low-fat (LF)- and high-fat (HF)-fed mice. Two cohorts (separated by 2 weeks) of male C57BL/6J mice (n = 24 in each cohort, 6/group/cohort; 6 weeks old) were separated into four weight-matched groups and fed either a LF (10 % fat/kcal) or HF (45% fat/kcal) with or without supplementation of MB (LF/MB or HF/MB) at 0.25% (w/v) in drinking water for 6 weeks. Metabolic phenotypes (body weight and adiposity), intestinal inflammation, feeding behavior, and fecal microbiome and metabolites were measured. Despite identical genetic and experimental conditions, we found marked differences between cohorts in the response (body weight gain, adiposity, and intestinal permeability) to HF-diet and MB. Notably, the composition of the gut microbiota was significantly different between cohorts, characterized by lower species richness and differential abundance of a large number of taxa, including subtaxa from five phyla, including increased abundance of the genera Bacteroides, Proteobacteria, and Parasutterella in cohort 2 compared to cohort 1. These differences may have contributed to the differential response in intestinal permeability to the HF diet in cohort 2. MB supplementation had no significant effect on metabolic phenotype, but there was a trend to protect from HF-induced impairments in intestinal barrier function in cohort 1 and in sensitivity to cholecystokinin (CCK) in both cohorts. These data support the concept that microbiota composition may have a crucial effect on metabolic responses of a host to dietary interventions and highlight the importance of taking steps to ensure reproducibility in rodent studies.

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