Junrui Cheng

Editorial: New advances in dietary fibers and their role in metabolic, digestive, and immune health

Colorectal disturbances encompass a variety of disorders that impact the colon and rectum, such as colitis and colon cancer. Butyrate, a short-chain fatty acid, plays a pivotal role in supporting gut health by nourishing colonocytes, promoting barrier function, modulating inflammation, and fostering a balanced microbiome. Increasing colorectal butyrate concentration may serve as a critical strategy to improve colon function and reduce the risk of colorectal disturbances. Butyrylated high-amylose maize starch (HAMSB) is an edible ingredient that efficiently delivers butyrate to the colon. HAMSB is developed by esterifying a high-amylose starch backbone with butyric anhydride. With a degree of substitution of 0.25, each hydroxy group of HAMSB is substituted by a butyryl group in every four D-glucopyranosyl units. In humans, the digestibility of HAMSB is 68% (w/w), and 60% butyrate molecules attached to the starch backbone is absorbed by the colon. One clinical trial yielded two publications, which showed that HAMSB significantly reduced rectal O⁶-methyl-guanine adducts and epithelial proliferation induced by the high protein diet. Fecal microbial profiles were assessed in three clinical trials, showing that HAMSB supplementation was consistently linked to increased abundance of Parabacteroides distasonis. In animal studies, HAMSB was effective in reducing the risk of diet- or AOM-induced colon cancer by reducing genetic damage, but the mechanisms differed. HAMSB functioned through affecting cecal ammonia levels by modulating colon pH in diet-induced cancer, while it ameliorated chemical-induced colon cancer through downregulating miR19b and miR92a expressions and subsequently activating the caspase-dependent apoptosis. Furthermore, animal studies showed that HAMSB improved colitis via regulating the gut immune modulation by inhibiting histone deacetylase and activating G protein-coupled receptors, but its role in bacteria-induced colon colitis requires further investigation. In conclusion, HAMSB is a food ingredient that may deliver butyrate to the colon to support colon health. Further clinical trials are warranted to validate earlier findings and determine the minimum effective dose of HAMSB.

Nutritional biomarkers can be used as important indicators of nutritional status and play crucial roles in the prevention as well as prognosis optimization of various metabolism-related diseases. Measuring dietary with the deployment of biomarker assessments provides quantitative nutritional information that can better predict the health outcomes. With the increased availability of nutritional biomarkers and the development of assessment tools, the specificity and sensitivity of nutritional biomarkers have been greatly improved. This enables efficient disease surveillance in nutrition research. A wide range of biomarkers have been used in different types of studies, including clinical trials, observational studies, and qualitative studies, to reflect the relationship between diet and health. Through a comprehensive literature search, we reviewed the well-established nutritional biomarkers of vitamins, minerals, and phytonutrients, and their association with epidemiological studies, to better understand the role of nutrition in health and disease.

Background: Carotenoids are naturally occurring pigments accounting for brilliant colors of fruits and vegetables. Dietary carotenoids can exert anti‐inflammatory properties in humans. Carotenoids are absorbed in the small intestine. A significant amount of the carotenoids may escape absorption and can be transferred to the colon. Carotenoids can be further released, or additional conversions can happen within colon epithelial cells, colonocytes. Objective: A major research gap exists regarding the effects of dietary carotenoids in the colonocytes. We propose to address it by examining the effects of major dietary carotenoid, β‐carotene (BC), in colonocytes. Our central hypothesis is that BC can modulate the inflammatory transcription factor, nuclear factor‐kappa B (NF‐κB). Methods: To address our hypothesis, we examined the function of BC in the lipopolysaccharide (LPS)/toll‐like receptor (TLR4) signaling pathway using in vitro human colon epithelial cell model. First, HT‐29 cells were primed with interferon‐γ, then subjected to LPS and BC at the same time. Subsequently, we employed western blotting to biochemically evaluate expressions of TLR4 and its co‐receptor, CD14. Additionally, we examined the signals of NF‐κB p65 subunit. We also studied the impact of BC on the essential tight junction proteins, including claudin‐1 and occludin. Then, we employed another analytical biochemistry assay, enzyme‐linked immunosorbent assay (ELISA) to illustrate the effect of BC on the release of pro‐inflammatory cytokines such as interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), and tumor necrosis factor alpha (TNFα). Next, we decided to perform immunocytochemistry experiments to visualize the signals of claudin‐1. Finally, we used high‐performance liquid chromatography, C30 reversed‐phase column, a mobile phase of methanol, methyl‐tert‐butyl‐ether, and acetonitrile with gradient separation and visible detection at 475 nm to separate BC in cell culture supernatants. Results: β‐Carotene was found to decrease LPS‐induced intestinal inflammation in colonocytes. It also enhanced gut barrier function via promoting the levels of tight junction proteins, both qualitatively and quantitatively. ELISA assays demonstrated that BC reduced the release of pro‐inflammatory cytokines. Finally, HPLC portrayed that the anti‐inflammatory activity of BC was mostly stemming from itself. Conclusions: Overall, this study's findings suggest that BC could be a bioactive compound within colonocytes as it could be an effective player in colonic inflammation. BC could also buttress the intestinal barrier integrity when colonocytes were challenged with LPS. These findings will enhance our knowledge of how BC functions in colonic inflammation and its role in gut barrier integrity.

Lycopene, a naturally occurring non-provitamin A carotenoid pigment, is responsible for the red to pink colors in tomato, watermelon, red bell peppers, and pink guava. There are many health benefits attributed to lycopene including but not limited to its antioxidant activity. According to the American Lung Association’s State of Lung Cancer, lung cancer is still the leading cause of cancer death in the United States. Other chronic lung diseases such as asthma, emphysema, and chronic obstructive pulmonary disease are high prevalence. This chapter summarizes lycopene’s protective role against lung diseases in both in vitro and in vivo studies. While it has been demonstrated that circulating lycopene can be used as a biomarker for several lung diseases, further studies are warranted to establish that. We aim to provide insights into how lycopene can remedy for lung diseases, including lung cancer.

Background: Oxidative stress plays a critical role in lung cancer progression. Carotenoids are efficient antioxidants. The objective of this study was to explore the efficacy of all-trans retinoic acid (ATRA) and carotenoids in cigarette smoke-induced oxidative stress within A549 human lung cancer epithelial cells. Methods: A549 cells were pretreated with 1-nM, 10-nM, 100-nM, 1-μM and 10-μM ATRA, β-carotene (BC) and lycopene for 24 h, followed by exposure to cigarette smoke using a smoking chamber. Results: The OxyBlot analysis showed that smoking significantly increased oxidative stress, which was inhibited by lycopene at 1 nM and 10 nM (p < 0.05). In the cells exposed to smoke, lycopene increased 8-oxoguanine DNA glycosylase (OGG1) expression at 1 nM, 10 nM, 100 nM, and 1 μM (p < 0.05), but not at 10 μM. Lycopene at lower doses also improved Nei like DNA glycosylases (NEIL1, NEIL2, NEIL3), and connexin-43 (Cx43) protein levels (p < 0.05). Interestingly, lycopene at lower concentrations promoted OGG1 expression within the cells exposed to smoke to an even greater extent than the cells not exposed to smoke (p < 0.01). This may be attributed to the increased SR-B1 mRNA levels with cigarette smoke exposure (p < 0.05). Conclusions: Lycopene treatment at a lower dosage could inhibit smoke-induced oxidative stress and promote genome stability. These novel findings will shed light on the molecular mechanism of lycopene action against lung cancer.

Chronic gastritis is observed in almost half world population. Traditional medications against chronic gastritis might produce adverse effects, so alternative nutritional strategies are needed to prevent the aggravation of gastric mucosal damage. The aim of this study is to evaluate the protective effect of the combination of wheat peptides and fucoidan (WPF) on adults diagnosed with chronic superficial gastritis in a randomized, double-blind, placebo-controlled clinical trial.

Scope: Beta‐carotene‐15,15′‐oxygenase (BCO1) and beta‐carotene‐9′,10′‐oxygenase (BCO2) metabolize lycopene to biologically active metabolites, which can ameliorate nonalcoholic fatty liver disease (NAFLD). We investigate the effects of tomato powder (TP containing substantial lycopene (2.3 mg/g)) on NAFLD development and gut microbiome in the absence of both BCO1 and BCO2 in mice.Method and results: BCO1^−/−/BCO2^−/− double knockout mice were fed a high fat diet (HFD) alone (n = 9) or with TP feeding (n = 9) for 24 weeks. TP feeding significantly reduced pathological severity of steatosis and hepatic triglyceride levels in BCO1^−/−/BCO2^−/− mice (p < 0.04 vs HFD alone). This was associated with increased SIRT1 activity, nicotinamide phosphoribosyltransferase expression and AMP‐activated protein kinase phosphorylation, and subsequently decreased lipogenesis, hepatic fatty acid uptake, and increasing fatty acid β‐oxidation (p < 0.05). TP feeding significantly decreased mRNA expression of proinflammatory genes (tnf‐α, il‐1β, and il‐6) in both liver and mesenteric adipose tissue, which were associated with increased plasma adiponectin and hepatic adiponectin receptor‐2. Multiplexed 16S rRNA gene sequencing was performed using DNA extracted from cecum fecal samples. TP feeding increased microbial richness and decreased relative abundance of the genus Clostridium.Conclusion: Dietary TP can inhibit NAFLD independent of carotenoid cleavage enzymes, potentially through increasing SIRT1 activity and adiponectin production and decreasing Clostridium abundance.