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Randomized Clinical Trial: Probiotics Alleviated Oral-Gut Microbiota Dysbiosis and Thyroid Hormone Withdrawal-Related Complications in Thyroid Cancer Patients Before Radioiodine Therapy Following Thyroidectomy.
Lin, B, Zhao, F, Liu, Y, Wu, X, Feng, J, Jin, X, Yan, W, Guo, X, Shi, S, Li, Z, et al
Frontiers in endocrinology. 2022;13:834674
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The occurrence of thyroid cancer has increased in recent years. Part of the treatment for this disease is removal of the thyroid gland and then the administration of radioactive iodine. To help aid the uptake of radioactive iodine, individuals may need to withdraw from their thyroid hormone therapy, known as thyroid hormone withdrawal (THW). This is however accompanied by side effects such as fatigue, constipation, and weight gain, all of which have been hypothesised to be due to gut microbiota dysbiosis. This randomised control trial aimed to determine any gut and oral microbiota signatures in 50 individuals who have undergone THW because of thyroid cancer and to see if probiotics have any beneficial effects. The results showed that gut and oral microbiota diversity was decreased after THW. Upon the administration of probiotics, diversity was restored, energy and blood lipid levels were improved, and weight gain and a dry mouth were alleviated. It was concluded that probiotics reduce the occurrence of side effects following THW, which may be related to the modification of oral and gut microbiota diversity. This study could be used by healthcare professionals to understand that probiotics may be of benefit to improve the side effects associated with THW in individuals with thyroid cancer.
Abstract
BACKGROUND Thyroid hormone withdrawal (THW) in postoperative thyroid cancer patients who need always accompanied by complications (e.g., dyslipidemia and constipation). At present, there are no effective and safe means to alleviate these complications. PURPOSE We aimed to assess the oral-gut microbiota profiles in THW patients then investigate whether probiotics could alleviating alleviate THW related complications and investigate whether these therapeutic effects were associated with the oral-gut microbiota state. METHODS Fifty eligible thyroid carcinoma patients undergoing thyroidectomy were randomly assigned to receive probiotics or placebo during THW. Complications were assessed through validated questionnaires and plasma lipid indicators. The complex probiotics preparation was composed of Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis, and Bacillus cereus. RESULTS Probiotics alleviated lack of energy, constipation, weight gain, and dry mouth and decreased the levels of fecal/serum LPS and plasma lipid indicators (total cholesterol, triglycerides, low-density lipoprotein, and apolipoprotein A) (P < 0.05). Gut and oral microbial diversity were significantly decreased after THW, while an increased microbial dysbiosis index (MDI) was observed. Probiotics distinctly restored the gut and oral microbial diversity. Increased Holdemanella, Enterococcus, and Coprococcus_2, while decreased Fusobacterium, Eubacterium_ruminantium_group, Ruminococcus_1, and Parasutterella in the gut were found after probiotics intervention. Lack of energy, constipation, weight gain, and dyslipidemia were seen to be related to the above microbiota. In addition, probiotics reduced oral Prevotella_9, Haemophilus, Fusobacterium, and Lautropia, which were positively correlated with the occurrence of dry mouth. CONCLUSION Probiotics reduce the incidence of complications in patients after THW, which may be related to modifying the oral and gut microbiota. CLINICAL TRIAL REGISTRATION [https://clinicaltrials.gov/], identifier America Clinical Trial Registry NCT03574051.
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Heat-stabilised rice bran consumption by colorectal cancer survivors modulates stool metabolite profiles and metabolic networks: a randomised controlled trial.
Brown, DG, Borresen, EC, Brown, RJ, Ryan, EP
The British journal of nutrition. 2017;117(9):1244-1256
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Colorectal cancer (CRC) is the third most common cancer in the world. Rice bran is high in phytochemicals, fibre and other bioactive compounds that may have potential to reduce cancer formation. Rice bran consumption has been shown to reduce CRC growth in mice, as well as alter the stool microbiome in humans. This alteration of the gut microbiome and the metabolic end products produced by it is thought to provide positive health benefits in terms of CRC development. This randomised controlled trial with CRC survivors included daily consumption of 30g/day of rice bran for 28 days in the intervention group, consisting of 9 participants. No rice bran was consumed in the control group of 10 participants. The aim of the study was to identify changes in metabolites that may have potential to reduce the risk of CRC, in the stool samples given by the participants after consuming rice bran, as well as to understand the differences in stool metabolites in the intervention and control groups. The authors found that rice bran consumption led to changes in 93 metabolites, 33 of which increased, while 60 metabolites decreased after 4 weeks of consumption. Metabolic pathways affected included advanced glycation end products, steroid metabolism, primary bile acid metabolism, leucine, isoleucine and valine metabolism, methionine, cysteine, S-adenosyl methionine and taurine metabolism, inositol metabolism, vitamin B6 metabolism and benzoate metabolism. The authors hypothesise that these metabolic changes may have potential for the prevention of cancer and they should be further explored in larger studies.
Abstract
Rice bran (RB) consumption has been shown to reduce colorectal cancer (CRC) growth in mice and modify the human stool microbiome. Changes in host and microbial metabolism induced by RB consumption was hypothesised to modulate the stool metabolite profile in favour of promoting gut health and inhibiting CRC growth. The objective was to integrate gut microbial metabolite profiles and identify metabolic pathway networks for CRC chemoprevention using non-targeted metabolomics. In all, nineteen CRC survivors participated in a parallel randomised controlled dietary intervention trial that included daily consumption of study-provided foods with heat-stabilised RB (30 g/d) or no additional ingredient (control). Stool samples were collected at baseline and 4 weeks and analysed using GC-MS and ultra-performance liquid chromatography-MS. Stool metabolomics revealed 93 significantly different metabolites in individuals consuming RB. A 264-fold increase in β-hydroxyisovaleroylcarnitine and 18-fold increase in β-hydroxyisovalerate exemplified changes in leucine, isoleucine and valine metabolism in the RB group. A total of thirty-nine stool metabolites were significantly different between RB and control groups, including increased hesperidin (28-fold) and narirutin (14-fold). Metabolic pathways impacted in the RB group over time included advanced glycation end products, steroids and bile acids. Fatty acid, leucine/valine and vitamin B6 metabolic pathways were increased in RB compared with control. There were 453 metabolites identified in the RB food metabolome, thirty-nine of which were identified in stool from RB consumers. RB consumption favourably modulated the stool metabolome of CRC survivors and these findings suggest the need for continued dietary CRC chemoprevention efforts.
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Feasibility outcomes of a presurgical randomized controlled trial exploring the impact of caloric restriction and increased physical activity versus a wait-list control on tumor characteristics and circulating biomarkers in men electing prostatectomy for prostate cancer.
Demark-Wahnefried, W, Nix, JW, Hunter, GR, Rais-Bahrami, S, Desmond, RA, Chacko, B, Morrow, CD, Azrad, M, Frugé, AD, Tsuruta, Y, et al
BMC cancer. 2016;16:61
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There is a strong body of evidence associating obesity and increased risk for more aggressive and progressive cancer. This paper aims to assess the feasibility of a presurgical diet and exercise weight loss intervention in men with newly-diagnosed prostate cancer who elected for prostatectomy. It also aims to explore the intervention’s effects on tumour proliferation rates and other biomarkers. The 3-weeks randomised controlled study included 40 overweight or obese men newly-diagnosed with prostate cancer. Participants in experimental arm were assigned to a healthy energy-restricted diet versus wait-list control arm. All feasibility endpoints were achieved with accrual completed within 2 years, retention of 85%, adherence of 95% and no adverse events. Biologic outcomes were not included in this paper, as biological testing was still ongoing. Authors concluded that this study’s methods and data on feasibility could provide useful framework for the design of future trials. They also highlighted the importance of presurgical trials as a feasible and safe means to assess the impacts of diet and exercise on tumour tissue.
Abstract
BACKGROUND Obesity is associated with tumor aggressiveness and disease-specific mortality for more than 15 defined malignancies, including prostate cancer. Preclinical studies suggest that weight loss from caloric restriction and increased physical activity may suppress hormonal, energy-sensing, and inflammatory factors that drive neoplastic progression; however, exact mechanisms are yet to be determined, and experiments in humans are limited. METHODS We conducted a randomized controlled trial among 40 overweight or obese, newly-diagnosed prostate cancer patients who elected prostatectomy to explore feasibility of a presurgical weight loss intervention that promoted a weight loss of roughly one kg. week(-1) via caloric restriction and physical activity, as well as to assess effects on tumor biology and circulating biomarkers. Measures of feasibility (accrual, retention, adherence, and safety) were primary endpoints. Exploratory aims were directed at the intervention's effect on tumor proliferation (Ki-67) and other tumor markers (activated caspase-3, insulin and androgen receptors, VEGF, TNFβ, NFκB, and 4E-BP1), circulating biomarkers (PSA, insulin, glucose, VEGF, TNFβ, leptin, SHBG, and testosterone), lymphocytic gene expression of corresponding factors and cellular bioenergetics in neutrophils, and effects on the gut microbiome. Consenting patients were randomized in a 1:1 ratio to either: 1) weight loss via a healthful, guidelines-based diet and exercise regimen; or 2) a wait-list control. While biological testing is currently ongoing, this paper details our methods and feasibility outcomes. RESULTS The accrual target was met after screening 101 cases (enrollment rate: 39.6%). Other outcomes included a retention rate of 85%, excellent adherence (95%), and no serious reported adverse events. No significant differences by age, race, or weight status were noted between enrollees vs. non-enrollees. The most common reasons for non-participation were "too busy" (30%), medical exclusions (21%), and "distance" (16%). CONCLUSIONS Presurgical trials offer a means to study the impact of diet and exercise interventions directly on tumor tissue, and other host factors that are feasible and safe, though modifications are needed to conduct trials within an abbreviated period of time and via distance medicine-based approaches. Pre-surgical trials are critical to elucidate the impact of lifestyle interventions on specific mechanisms that mediate carcinogenesis and which can be used subsequently as therapeutic targets. TRIAL REGISTRATION NCT01886677.
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Dietary sulforaphane-rich broccoli sprouts reduce colonization and attenuate gastritis in Helicobacter pylori-infected mice and humans.
Yanaka, A, Fahey, JW, Fukumoto, A, Nakayama, M, Inoue, S, Zhang, S, Tauchi, M, Suzuki, H, Hyodo, I, Yamamoto, M
Cancer prevention research (Philadelphia, Pa.). 2009;2(4):353-60
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Helicobacter pylori infection is strongly associated with stomach cancer. Broccoli sprouts are rich in glucoraphanin, the precursor of sulforaphane and have been shown to be bactericidal against Helicobacter pylori infections. This study aimed to evaluate efficacy of broccoli sprouts in reducing H. pylori infection in high-salt, H. pylori–infected mice and infected humans. 6-wk-old mice were infected with H-Pylori and consumed a high salt diet for 2 months. High-salt diets exaggerate H. pylori–induced gastritis in mice. Mice were randomised into 2 groups receiving either broccoli sprouts in water or plain drinking water. Mice had free food access. 50 H. pylori–positive human volunteers whose endoscopy showed gastritis were randomised to consume 70 g/d of broccoli sprouts or equivalent of alfalfa sprouts for 8 weeks. Self reported compliance (95%) was confirmed by urine sample. In mice consuming the broccoli sprout water, inflammation was reduced, as were the cytokines unregulated by H. pylori infection. In humans, inflammation in the gastric lumen was significantly reduced in the broccoli sprout group only. Both stool and breath markers of H pylori were significantly lower when compared to control. The authors conclude that intake of sulforaphane-rich broccoli sprouts for 2 months reduces H. pylori colonization in mice and improves infection in H pylori positive mice and humans.
Abstract
The isothiocyanate sulforaphane [SF; 1-isothiocyanato-4(R)-methylsulfinylbutane] is abundant in broccoli sprouts in the form of its glucosinolate precursor (glucoraphanin). SF is powerfully bactericidal against Helicobacter pylori infections, which are strongly associated with the worldwide pandemic of gastric cancer. Oral treatment with SF-rich broccoli sprouts of C57BL/6 female mice infected with H. pylori Sydney strain 1 and maintained on a high-salt (7.5% NaCl) diet reduced gastric bacterial colonization, attenuated mucosal expression of tumor necrosis factor-alpha and interleukin-1beta, mitigated corpus inflammation, and prevented expression of high salt-induced gastric corpus atrophy. This therapeutic effect was not observed in mice in which the nrf2 gene was deleted, strongly implicating the important role of Nrf2-dependent antioxidant and anti-inflammatory proteins in SF-dependent protection. Forty-eight H. pylori-infected patients were randomly assigned to feeding of broccoli sprouts (70 g/d; containing 420 micromol of SF precursor) for 8 weeks or to consumption of an equal weight of alfalfa sprouts (not containing SF) as placebo. Intervention with broccoli sprouts, but not with placebo, decreased the levels of urease measured by the urea breath test and H. pylori stool antigen (both biomarkers of H. pylori colonization) and serum pepsinogens I and II (biomarkers of gastric inflammation). Values recovered to their original levels 2 months after treatment was discontinued. Daily intake of sulforaphane-rich broccoli sprouts for 2 months reduces H. pylori colonization in mice and improves the sequelae of infection in infected mice and in humans. This treatment seems to enhance chemoprotection of the gastric mucosa against H. pylori-induced oxidative stress.