A Bronze-Tomato Enriched Diet Affects the Intestinal Microbiome under Homeostatic and Inflammatory Conditions

Inflammatory bowel diseases (IBD) are debilitating chronic inflammatory disorders that develop as a result of a defective immune response toward intestinal bacteria. Intestinal dysbiosis is associated with the onset of IBD and has been reported to persist even in patients in deep remission. We investigated the possibility of a dietary-induced switch to the gut microbiota composition using Winnie mice as a model of spontaneous ulcerative colitis and chow enriched with 1% Bronze tomato. We used the near isogenic tomato line strategy to investigate the effects of a diet enriched in polyphenols administered to mild but established chronic intestinal inflammation. The Bronze-enriched chow administered for two weeks was not able to produce any macroscopic effect on the IBD symptoms, although, at molecular level there was a significant induction of anti-inflammatory genes and intracellular staining of T cells revealed a mild decrease in IL17A and IFNγ production. Analysis of the microbial composition revealed that two weeks of Bronze enriched diet was sufficient to perturb the microbial composition of Winnie and control mice, suggesting that polyphenol-enriched diets may create unfavorable conditions for distinct bacterial species. In conclusion, dietary regimes enriched in polyphenols may efficiently support IBD remission affecting the intestinal dysbiosis.

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Loss of Nckx3 Exacerbates Experimental DSS-Induced Colitis in Mice through p53/NF-κB Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms22052645 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2645

Author(s):

Dinh Nam Tran ◽

Seon Myeong Go ◽

Seon-Mi Park ◽

Eui-Man Jung ◽

Eui-Bae Jeung

Keyword(s):

Immune Response ◽

Cellular Proliferation ◽

Intestinal Inflammation ◽

Critical Role ◽

Experimental Colitis ◽

Innate Immune ◽

Inflammatory Conditions ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Microarray Analyses

Inflammatory bowel diseases (IBDs) comprises a range of chronic inflammatory conditions of the intestinal tract. The incidence and prevalence of IBDs are increasing worldwide, but the precise etiology of these diseases is not completely understood. Calcium signaling plays a regulatory role in cellular proliferation. Nckx3, a potassium-dependent Na+/Ca2+ exchanger, is not only expressed in the brain but also in the aortic, uterine, and intestinal tissues, which contain abundant smooth muscle cells. This study investigated the role of Nckx3 in intestinal inflammation. Microarray analyses revealed the upregulation of the innate immune response-associated genes in the duodenum of Nckx3 knockout (KO) mice. The Nckx3 KO mice also showed an increase in IBD- and tumorigenesis-related genes. Using dextran sodium sulfate (DSS)-induced experimental colitis mice models, the Nckx3 KO mice showed severe colitis. Furthermore, the pathways involving p53 and NF-κB signaling were significantly upregulated by the absence of Nckx3. Overall, Nckx3 plays a critical role in the innate immune and immune response and may be central to the pathogenesis of IBD.

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Anthocyanins and intestinal barrier function: a review

Journal of Food Bioactives ◽

10.31665/jfb.2019.5175 ◽

2019 ◽

Vol 5 ◽

pp. 18-30 ◽

Cited By ~ 4

Author(s):

Jonathan C. Valdez ◽

Bradley W. Bolling

Keyword(s):

Barrier Function ◽

Intestinal Inflammation ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Barrier Dysfunction ◽

Intestinal Barrier Dysfunction ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Berry Anthocyanins ◽

Chronic Intestinal Inflammation

Chronic intestinal inflammation, occurring in inflammatory bowel diseases (IBD), is associated with compromised intestinal barrier function. Inflammatory cytokines disrupt tight junctions and increase paracellular permeability of luminal antigens. Thus, chronic intestinal barrier dysfunction hinders the resolution of inflammation. Dietary approaches may help mitigate intestinal barrier dysfunction and chronic inflammation. A growing body of work in rodent models of colitis has demonstrated that berry consumption inhibits chronic intestinal inflammation. Berries are a rich dietary source of polyphenolic compounds, particularly anthocyanins. However, berry anthocyanins have limited bioavailability and are extensively metabolized by the gut microbiota and host tissue. This review summarizes the literature regarding the beneficial functions of anthocyanin-rich berries in treating and preventing IBD. Here, we will establish the role of barrier function in the pathogenesis of IBD and how dietary anthocyanins and their known microbial catabolites modulate intestinal barrier function.

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Microbiota-independent immunological effects of non-digestible oligosaccharides in the context of inflammatory bowel diseases

Proceedings of The Nutrition Society ◽

10.1017/s0029665120006953 ◽

2020 ◽

Vol 79 (4) ◽

pp. 468-478 ◽

Cited By ~ 1

Author(s):

Stefania Del Fabbro ◽

Philip C. Calder ◽

Caroline E. Childs

Keyword(s):

Inflammatory Bowel Diseases ◽

Immune Cell ◽

Intestinal Inflammation ◽

Mechanisms Of Action ◽

Mucosal Inflammation ◽

Disease States ◽

Inflammatory Conditions ◽

Bowel Diseases ◽

Inflammatory Bowel

The aim of the present paper is to review the effects of non-digestible oligosaccharides (NDO) on immunity, focusing on their microbiota-independent mechanisms of action, as well as to explore their potential beneficial role in inflammatory bowel diseases (IBD). IBD are chronic, inflammatory conditions of the gastrointestinal tract. Individuals with IBD have an aberrant immune response to commensal microbiota, resulting in extensive mucosal inflammation and increased intestinal permeability. NDO are prebiotic fibres well known for their role in supporting intestinal health through modulation of the gut microbiota. NDO reach the colon intact and are fermented by commensal bacteria, resulting in the production of SCFA with immunomodulatory properties. In disease states characterised by increased gut permeability, prebiotics may also bypass the gut barrier and directly interact with intestinal and systemic immune cells, as demonstrated in patients with IBD and in infants with an immature gut. In vitro models show that fructooligosaccharides, inulin and galactooligosaccharides exert microbiota-independent effects on immunity by binding to toll-like receptors on monocytes, macrophages and intestinal epithelial cells and by modulating cytokine production and immune cell maturation. Moreover, animal models and human supplementation studies demonstrate that some prebiotics, including inulin and lactulose, might reduce intestinal inflammation and IBD symptoms. Although there are convincing preliminary data to support NDO as immunomodulators in the management of IBD, their mechanisms of action are still unclear and larger standardised studies need to be performed using a wider range of prebiotics.

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The Intestinal Fate of Citrus Flavanones and Their Effects on Gastrointestinal Health

Nutrients ◽

10.3390/nu11071464 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1464 ◽

Cited By ~ 21

Author(s):

Yala Stevens ◽

Evelien Van Rymenant ◽

Charlotte Grootaert ◽

John Van Camp ◽

Sam Possemiers ◽

...

Keyword(s):

Barrier Function ◽

Intestinal Inflammation ◽

Human Subjects ◽

Intestinal Barrier ◽

Intestinal Bacteria ◽

Intestinal Microbiome ◽

Intestinal Barrier Function ◽

Current Evidence ◽

Gastrointestinal Health ◽

Beneficial Effects

Citrus flavanones, with hesperidin and naringin as the most abundant representatives, have various beneficial effects, including anti-oxidative and anti-inflammatory activities. Evidence also indicates that they may impact the intestinal microbiome and are metabolized by the microbiota as well, thereby affecting their bioavailability. In this review, we provide an overview on the current evidence on the intestinal fate of hesperidin and naringin, their interaction with the gut microbiota, and their effects on intestinal barrier function and intestinal inflammation. These topics will be discussed as they may contribute to gastrointestinal health in various diseases. Evidence shows that hesperidin and naringin are metabolized by intestinal bacteria, mainly in the (proximal) colon, resulting in the formation of their aglycones hesperetin and naringenin and various smaller phenolics. Studies have also shown that citrus flavanones and their metabolites are able to influence the microbiota composition and activity and exert beneficial effects on intestinal barrier function and gastrointestinal inflammation. Although the exact underlying mechanisms of action are not completely clear and more research in human subjects is needed, evidence so far suggests that citrus flavanones as well as their metabolites have the potential to contribute to improved gastrointestinal function and health.

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Apple peel polyphenols: a key player in the prevention and treatment of experimental inflammatory bowel disease

Clinical Science ◽

10.1042/cs20160524 ◽

2016 ◽

Vol 130 (23) ◽

pp. 2217-2237 ◽

Cited By ~ 26

Author(s):

Marie-Claude Denis ◽

Denis Roy ◽

Pantea Rahmani Yeganeh ◽

Yves Desjardins ◽

Thibault Varin ◽

...

Keyword(s):

Fruits And Vegetables ◽

Intestinal Inflammation ◽

Therapeutic Effects ◽

Microbial Composition ◽

Beneficial Effects ◽

Apple Peel ◽

Bowel Diseases ◽

Clinical Benefits ◽

Inflammatory Bowel ◽

Underlying Mechanisms

Diets rich in fruits and vegetables may reduce oxidative stress (OxS) and inflammation via several mechanisms. These beneficial effects may be due to their high polyphenol content. The aims of the present study are to evaluate the preventive and therapeutic aspects of polyphenols in dried apple peel powder (DAPP) on intestinal inflammation while elucidating the underlying mechanisms and clinical benefits. Induction of intestinal inflammation in mice was performed by oral administration of the inflammatory agent dextran sulfate sodium (DSS) at 2.5% for 10 days. Physiological and supraphysiological doses of DAPP (200 and 400 mg/kg/day respectively) were administered by gavage for 10 days pre- and post-DSS treatment. DSS-mediated inflammation caused weight loss, shortening of the colon, dystrophic detachment of the epithelium, and infiltration of mono- and poly-morphonuclear cells in the colon. DSS induced an increase in lipid peroxidation, a down-regulation of antioxidant enzymes, an augmented expression of myeloperoxidase (MPO) and cyclooxygenase-2 (COX-2), an elevated production of prostaglandin E2 (PGE2) and a shift in mucosa-associated microbial composition. However, DAPP normalized most of these abnormalities in preventive or therapeutic situations in addition to lowering inflammatory cytokines while stimulating antioxidant transcription factors and modulating other potential healing pathways. The supraphysiological dose of DAPP in therapeutic situations also improved mitochondrial dysfunction. Relative abundance of Peptostreptococcaceae and Enterobacteriaceae bacteria was slightly decreased in DAPP-treated mice. In conclusion, DAPP exhibits powerful antioxidant and anti-inflammatory action in the intestine and is associated with the regulation of cellular signalling pathways and changes in microbiota composition. Evaluation of preventive and therapeutic effects of DAPP may be clinically feasible in individuals with intestinal inflammatory bowel diseases.

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Going Beyond Bacteria: Uncovering the Role of Archaeome and Mycobiome in Inflammatory Bowel Disease

Frontiers in Physiology ◽

10.3389/fphys.2021.783295 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yashar Houshyar ◽

Luca Massimino ◽

Luigi Antonio Lamparelli ◽

Silvio Danese ◽

Federica Ungaro

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Intestinal Inflammation ◽

The Body ◽

Inflammatory Conditions ◽

Relapsing Remitting ◽

Health And Disease ◽

Inflammatory Bowel ◽

Chronic Intestinal Inflammation

Inflammatory Bowel Disease (IBD) is a multifaceted class of relapsing-remitting chronic inflammatory conditions where microbiota dysbiosis plays a key role during its onset and progression. The human microbiota is a rich community of bacteria, viruses, fungi, protists, and archaea, and is an integral part of the body influencing its overall homeostasis. Emerging evidence highlights dysbiosis of the archaeome and mycobiome to influence the overall intestinal microbiota composition in health and disease, including IBD, although they remain some of the least understood components of the gut microbiota. Nonetheless, their ability to directly impact the other commensals, or the host, reasonably makes them important contributors to either the maintenance of the mucosal tissue physiology or to chronic intestinal inflammation development. Therefore, the full understanding of the archaeome and mycobiome dysbiosis during IBD pathogenesis may pave the way to the discovery of novel mechanisms, finally providing innovative therapeutic targets that can soon implement the currently available treatments for IBD patients.

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Intestinal microbiota and inflammatory bowel diseases

Journal of Korean Medical Association ◽

10.5124/jkma.2021.64.9.588 ◽

2021 ◽

Vol 64 (9) ◽

pp. 588-595

Author(s):

Chang Soo Eun

Keyword(s):

Intestinal Microbiota ◽

Inflammatory Bowel Diseases ◽

Intestinal Inflammation ◽

Microbial Composition ◽

Mucosal Permeability ◽

Next Generation Sequencing Technology ◽

Early Results ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

And Function

Background: The prevalence of inflammatory bowel diseases (IBD) has been rapidly increasing over the past several decades in Korea. IBD appears to be resulted from inappropriate and chronic activation of the mucosal immune system driven by stimuli such as intestinal microbiota and various environmental factors in genetically susceptible individuals.Current Concepts: Recent advances in next-generation sequencing technology have identified alterations in the composition and function of the intestinal microbiota in individuals with IBD. Dysbiosis in patients with IBD is characterized by decreased bacterial diversity combined with an expansion of putative aggressive species and a reduction in protective species. Altered microbial composition and function in IBD correlates with increased immune stimulation, epithelial dysfunction, or enhanced mucosal permeability. Thus, dysbiosis may play an essential role in the pathogenesis of IBD.Discussion and Conclusion: Although it is currently unclear whether dysbiosis is a cause or consequence of intestinal inflammation in IBD, several microbial-based and microbial-targeted therapies have yielded promising early results.

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Feeding a Low-protein Maternal Diet Affects Qinghai Bamei Piglet Jejunal Microbiome-metabolome Response

10.21203/rs.3.rs-591216/v1 ◽

2021 ◽

Author(s):

Jipeng Jin ◽

Liping Zhang ◽

Qian Chen ◽

Cunming Ma ◽

Jianlei Jia ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Bacterial Species ◽

Relative Weight ◽

Integrated Approach ◽

Intestinal Microbiome ◽

Rrna Gene ◽

Metabolic Profiles ◽

Microbial Composition ◽

Suckling Piglets

Abstract This experiment investigated the impacts of feeding a maternal low-CP concentration diet having iso-essential amino acids on new born suckling piglets intestinal microbial composition and metabolic profiles. The Bamei swine breed was selected due to high meat quality and flavor, but demonstrates slower growth rates which may be related to jejunal nutrient supply. Forty randomly selected purebred Bamei sows were divided into two groups and fed a low dietary CP (12%, LP) or a normal CP (14%, CON) diet, respectively, but formulated to contain similar (iso-) essential amino acid concentrations per current recommendations. At 21 days, 12 piglets were randomly selected from each treatment and euthanized with jejunum content samples collected. The 16S rRNA gene sequencing and mass spectrometry-based metabolomics profiling were combined as an integrated approach for evaluating the functional impact of maternal CP concentrations on piglet intestinal microbiome. Even though piglets demonstrated similar 0 to 21 d ADG among treatments, the jejunum relative weight, villus width, crypt depth and muscular thickness were increased (P < 0.05), while villus height, and villus height:crypt depth were reduced (P < 0.05) for the material LP compared to the maternal fed CON diet. Maternal CP concentrations can modify the intestinal microbial composition of Bamei suckling piglets. The relative abundances of the bacterial species Escherichia-Shigella, Actinobacillus, Clostridium_sensu_stricto_1, Veillonella, and Turicibacter were increased (P < 0.05) in the maternal LP fed diet compared with the maternal fed CON diet. Jejunal digesta metabolomics analysis indicated that several amino acids were metabolized (i.e. cys, met, tyr phe and trp), biosynthesized (arg phe, tyr, and trp), or degraded (lys) were enriched (P < 0.05) for the maternal fed LP compared with the maternal fed CON. Correlation analysis demonstrated that certain intestinal bacterial genera were highly related to the histomorphology and altered intestinal microbiota metabolites. In conclusion, maternal dietary CP concentrations in excess of protein and amino acid requirements not only altered suckling Bamei piglets histomorphology, microbial composition and function, but also modulated jejunum microbial metabolic profiles, which aids in understanding the beneficial effects when feeding a maternal LP diet on piglet intestinal health.

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Lactoferrin in the Prevention and Treatment of Intestinal Inflammatory Pathologies Associated with Colorectal Cancer Development

Cancers ◽

10.3390/cancers12123806 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3806

Author(s):

Antimo Cutone ◽

Giusi Ianiro ◽

Maria Stefania Lepanto ◽

Luigi Rosa ◽

Piera Valenti ◽

...

Keyword(s):

Colorectal Cancer ◽

Intestinal Inflammation ◽

Epidemiological Data ◽

Food Supplement ◽

Microbial Pathogens ◽

Intestinal Microbiome ◽

Cancer Development ◽

Wide Range ◽

Anti Inflammatory ◽

Chronic Intestinal Inflammation

The connection between inflammation and cancer is well-established and supported by genetic, pharmacological and epidemiological data. The inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis, have been described as important promoters for colorectal cancer development. Risk factors include environmental and food-borne mutagens, dysbalance of intestinal microbiome composition and chronic intestinal inflammation, with loss of intestinal epithelial barrier and enhanced cell proliferation rate. Therapies aimed at shutting down mucosal inflammatory response represent the foundation for IBDs treatment. However, when applied for long periods, they can alter the immune system and promote microbiome dysbiosis and carcinogenesis. Therefore, it is imperative to find new safe substances acting as both potent anti-inflammatory and anti-pathogen agents. Lactoferrin (Lf), an iron-binding glycoprotein essential in innate immunity, is generally recognized as safe and used as food supplement due to its multifunctionality. Lf possesses a wide range of immunomodulatory and anti-inflammatory properties against different aseptic and septic inflammatory pathologies, including IBDs. Moreover, Lf exerts anti-adhesive, anti-invasive and anti-survival activities against several microbial pathogens that colonize intestinal mucosa of IBDs patients. This review focuses on those activities of Lf potentially useful for the prevention/treatment of intestinal inflammatory pathologies associated with colorectal cancer development.

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Intervention withα-Ketoglutarate Ameliorates Colitis-Related Colorectal Carcinoma via Modulation of the Gut Microbiome

BioMed Research International ◽

10.1155/2019/8020785 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Si Li ◽

Chenxing Fu ◽

Yurong Zhao ◽

Jianhua He

Keyword(s):

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Intestinal Inflammation ◽

Intestinal Microbiome ◽

Protective Effects ◽

Opportunistic Pathogens ◽

Immunomodulatory Effects ◽

Chronic Intestinal Inflammation ◽

Antitumour Effects ◽

Necrosis Factor

The intestinal microbiome plays a crucial role in promoting intestinal health, and perturbations to its constitution may result in chronic intestinal inflammation and lead to colorectal cancer (CRC).α-Ketoglutarate is an important intermediary in the NF-κB-mediated inflammatory pathway that maintains intestinal homeostasis and prevents initiation of intestinal inflammation, a known precursor to carcinoma development. The objective of this study was to assess the potential protective effects ofα-ketoglutarate intervention against CRC development, which may arise due to its known anti-inflammatory and antitumour effects. CRC was induced in C57BL/6 mice using azoxymethane (AOM) and dextran sulfate sodium (DSS). Tumour frequency, histological rating, and colonic microbiota were assessed in colonic samples. The findings demonstrated thatα-ketoglutarate offered significant protection against CRC development in mice. Furthermore,α-ketoglutarate also exhibited immunomodulatory effects mediated via downregulation of interleukin (IL)-6, IL-22, tumour necrosis factor (TNF)-α, and IL-1βcytokines. Finally, intervention withα-ketoglutarate tended to minimise the frequency of opportunistic pathogens (EscherichiaandEnterococcus) while increasing the populations ofAkkermansia, Butyricicoccus,Clostridium,andRuminococcus. Taken together, our findings show that dietaryα-ketoglutarate intervention may protect against inflammation-related CRC.

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