Intervention with<i>α</i>-Ketoglutarate Ameliorates Colitis-Related Colorectal Carcinoma via Modulation of the Gut Microbiome

Li, Si; Fu, Chenxing; Zhao, Yurong; He, Jianhua

doi:10.1155/2019/8020785

Cited by 24 publications

(28 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A. muciniphila , a species that plays a beneficial role in inflammation and was previously reported to be increased in murine models of IBDs and to mediate the anti-inflammatory effects of several treatments on these models ( Bian et al, 2019 ; Li et al, 2019 ; Zhai R. et al, 2019 ; Zhang et al, 2019 ), was increased by DSS only at d14, suggesting that this effect might represent a potentially adaptive and protective mechanism intervening the resolution of inflammation. Importantly, this effect was rendered statistically significant also at d8 by a combination of per se ineffective doses of FO and CBD, but also by the single treatments.…”

Section: Discussionmentioning

confidence: 99%

Fish Oil, Cannabidiol and the Gut Microbiota: An Investigation in a Murine Model of Colitis

Silvestri

Pagano

Lacroix³

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

Inflammatory bowel disorders can be associated with alterations in gut microbiota (dysbiosis) and behavioral disturbances. In experimental colitis, administration of fish oil (FO) or cannabinoids, such as cannabidiol (CBD), reduce inflammation. We investigated the effect of combined FO/CBD administration on inflammation and dysbiosis in the dextran sulphate sodium (DSS) model of mouse colitis, which also causes behavioral disturbances. Colitis was induced in CD1 mice by 4% w/v DSS in drinking water for five consecutive days followed by normal drinking water. FO (20–75 mg/mouse) was administered once a day starting two days after DSS, whereas CBD (0.3–30 mg/kg), alone or after FO administration, was administered once a day starting 3 days after DSS, until day 8 (d8) or day 14 (d14). Inflammation was assessed at d8 and d14 (resolution phase; RP) by measuring the Disease Activity Index (DAI) score, change in body weight, colon weight/length ratio, myeloperoxidase activity and colonic interleukin (IL)-1β (IL-1β), IL-10, and IL-6 concentrations. Intestinal permeability was measured with the fluorescein isothiocyanate-dextran. Behavioral tests (novel object recognition (NOR) and light/dark box test) were performed at d8. Fecal microbiota composition was determined by ribosomal 16S DNA sequencing of faecal pellets at d8 and d14. DSS-induced inflammation was stronger at d8 and accompanied by anxiety-like behavior and impaired recognition memory. FO (35, 50, 75 mg/mouse) alone reduced inflammation at d8, whereas CBD alone produced no effect at any of the doses tested; however, when CBD (3, 10 mg/kg) was co-administered with FO (75 mg/mouse) inflammation was attenuated. FO (20 mg/mouse) and CBD (1 mg/kg) were ineffective when given alone, but when co-administered reduced all inflammatory markers and the increased intestinal permeability at both d8 and d14, but not the behavioral impairments. FO, CBD, and their combination affected gut bacteria taxa that were not affected by DSS per se . Akkermansia muciniphila , a species suggested to afford anti-inflammatory action in colitis, was increased by DSS only at d14, but its levels were significantly elevated by all treatments at d8. FO and CBD co-administered at per se ineffective doses reduce colon inflammation, in a manner potentially strengthened by their independent elevation of Akkermansia muciniphila .

show abstract

Section: Discussionmentioning

confidence: 99%

Fish Oil, Cannabidiol and the Gut Microbiota: An Investigation in a Murine Model of Colitis

Silvestri

Pagano

Lacroix³

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Curcumin administration, at the highest dose, reduced or eliminated colon tumor burden, increasing Lactobacilli and reducing Coriobacterales. It has also been clearly demonstrated that curcumin treatment reduces several Ruminococcus species [108]; this represents an interesting finding because increased population of Ruminococcus species has been linked to CRC occurrence [90,109], even if the pathogenic role of Ruminococcus in cancer development has not been yet fully clarified. Moreover, in mice treated with a mutagenic compound, dietary curcumin was able to restore to control levels the amount of Lactobacilli [102], which have been shown to possess antitumoral function [110].…”

Section: Curcumin Favors Beneficial Bacterial Strains In Gut Microbiotamentioning

confidence: 92%

“…There is growing evidence that any perturbation in gut microbiota composition (dysbiosis), associated with a reduced diversity and the predominance of a few pathogenic taxa, is closely linked to many human diseases [88][89][90]. In particular, dysbiosis has been related to pathological gastrointestinal conditions, such as inflammatory bowel disease and colorectal cancer (CRC) [91,92], but also to obesity, diabetes, asthma, and allergies [93,94].…”

Section: Gut Microbiotamentioning

confidence: 99%

Interaction between Gut Microbiota and Curcumin: A New Key of Understanding for the Health Effects of Curcumin

2020

View full text Add to dashboard Cite

Curcumin, a lipophilic polyphenol contained in the rhizome of Curcuma longa (turmeric), has been used for centuries in traditional Asian medicine, and nowadays it is widely used in food as dietary spice worldwide. It has received considerable attention for its pharmacological activities, which appear to act primarily through anti-inflammatory and antioxidant mechanisms. For this reason, it has been proposed as a tool for the management of many diseases, among which are gastrointestinal and neurological diseases, diabetes, and several types of cancer. However, the pharmacology of curcumin remains to be elucidated; indeed, a discrepancy exists between the well-documented in vitro and in vivo activities of curcumin and its poor bioavailability and chemical instability that should limit any therapeutic effect. Recently, it has been hypothesized that curcumin could exert direct regulative effects primarily in the gastrointestinal tract, where high concentrations of this polyphenol have been detected after oral administration. Consequently, it might be hypothesized that curcumin directly exerts its regulatory effects on the gut microbiota, thus explaining the paradox between its low systemic bioavailability and its wide pharmacological activities. It is well known that the microbiota has several important roles in human physiology, and its composition can be influenced by a multitude of environmental and lifestyle factors. Accordingly, any perturbations in gut microbiome profile or dysbiosis can have a key role in human disease progression. Interestingly, curcumin and its metabolites have been shown to influence the microbiota. It is worth noting that from the interaction between curcumin and microbiota two different phenomena arise: the regulation of intestinal microflora by curcumin and the biotransformation of curcumin by gut microbiota, both of them potentially crucial for curcumin activity. This review summarizes the most recent studies on this topic, highlighting the strong connection between curcumin and gut microbiota, with the final aim of adding new insight into the potential mechanisms by which curcumin exerts its effects.

show abstract

“…Lastly, supplementation with α-ketoglutarate, an important intermediary in the nuclear factor kappa light chain enhancer of activated B cells (NF-κB)-mediated inflammatory pathway, offered significant protection against CRC development in mice. Thus, α-ketoglutarate not only exhibited immunomodulatory effects mediated via the downregulation of IL-6, IL-22, TNF-α, and IL-1β cytokines but also minimized the frequency of opportunistic pathogens ( Escherichia and Enterococcus ), while it increased the populations of Akkermansia , Butyricicoccus , Clostridium , and Ruminococcus , suggesting that dietary α-ketoglutarate intervention may protect against inflammation-related CRC [ 109 ].…”

Section: Clinical Applications Of the Gut Microbiota Modulation Fomentioning

confidence: 99%

Gut Microbiota Manipulation as a Tool for Colorectal Cancer Management: Recent Advances in Its Use for Therapeutic Purposes

Perillo

Amoroso

Strati

et al. 2020

IJMS

View full text Add to dashboard Cite

Colorectal cancer (CRC) is a multifaceted disease influenced by both environmental and genetic factors. A large body of literature has demonstrated the role of gut microbes in promoting inflammatory responses, creating a suitable microenvironment for the development of skewed interactions between the host and the gut microbiota and cancer initiation. Even if surgery is the primary therapeutic strategy, patients with advanced disease or cancer recurrence after surgery remain difficult to cure. Therefore, the gut microbiota has been proposed as a novel therapeutic target in light of recent promising data in which it seems to modulate the response to cancer immunotherapy. The use of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics, and fecal microbiota transplantation, is therefore considered to support current therapies in CRC management. In this review, we will discuss the importance of host−microbe interactions in CRC and how promoting homeostatic immune responses through microbe-targeted therapies may be useful in preventing/treating CRC development.

show abstract

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

Cited by 24 publications

References 41 publications

Fish Oil, Cannabidiol and the Gut Microbiota: An Investigation in a Murine Model of Colitis

Fish Oil, Cannabidiol and the Gut Microbiota: An Investigation in a Murine Model of Colitis

Interaction between Gut Microbiota and Curcumin: A New Key of Understanding for the Health Effects of Curcumin

Gut Microbiota Manipulation as a Tool for Colorectal Cancer Management: Recent Advances in Its Use for Therapeutic Purposes

Contact Info

Product

Resources

About