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The Role of Genetically Engineered Probiotics for Treatment of Inflammatory Bowel Disease: A Systematic Review.
Zhang, T, Zhang, J, Duan, L
Nutrients. 2023;15(7)
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Inflammatory bowel disease (IBD), largely classified as Crohn’s disease (CD) or ulcerative colitis (UC), is a chronic intestinal inflammatory disorder mediated by genetic, immune, microbial, and environmental factors. The aim of this study was to summarise the efficacy of different genetically modified probiotics compared to wild-type probiotics in the treatment of IBD in animal models and patients and to investigate the specific effects and main mechanisms involved. This study was a systematic review of forty-five preclinical studies and one clinical study. Results showed a protective effect of genetically modified organisms (gm) probiotics in colitis. Several protective mechanisms have been identified: reduction of the pro- to anti-inflammatory cytokine ratio in colonic tissue and plasma, modulation of the activity of oxidative stress in the colon, improvement of intestinal barrier integrity, modulation of the diversity and composition of gut microbiota, and production of favourable metabolites, including short-chain fatty acids, by beneficial bacteria. Authors concluded that gm probiotics are more effective and safer than wild-type probiotics, to facilitate clinical translation.
Expert Review
Conflicts of interest:
None
Take Home Message:
Conclusions of this review were largely based on mouse models and although treatment using probiotics is generally considered safe in humans, with only minor side-effects (flatulence), practitioners need to be aware that in an IBD population the use of GM formulations might not be completely without risk.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This paper summarises the efficacy of specific genetically modified (GM) probiotic formulations for Inflammatory Bowel Disease (IBD) when compared to wild type probiotics. The aim was to ascertain what specific effects and mechanisms such probiotics have on IBD symptomatology.
Methods
- A total of 46 published articles were included; 45 mouse experimental models (induced acute or chronic colitis) (n=15-130) and 1 human IBD population clinical trial (n=10)
- The effect of GM probiotics were compared to placebo and wild-type probiotics in trials including preclinical studies, randomised controlled trials and cohort studies
- Animals received probiotics via gastric gavage (105 - 4 x 1012 CFU) for 3-6 weeks
- The human placebo-uncontrolled trial lasted 7 days and patients received 10 GM capsules of L.lactis (1 x 1010 CFU) twice daily.
Results
- GM probiotics that secrete immunoregulatory cytokines such as IL-10 appear to reduce intestinal damage
- The human trial using GM L.lactis resulted in 5 patients who went into complete clinical remission (CDAI, <150) with 3 patients exhibiting a clinical response (decrease in CDAI, >70). with only minor adverse events (flatulence)
- However, human cytokines that promote intestinal barrier function and epithelial restitution were not enhanced with oral administration of probiotics
- Two studies concluded that GM L.lactis and S.boulardii, that secrete atrial natriuretic peptide, might be the most effective options in supporting colitis
- GM L.casei resulted in faster recovery from weight loss in acute colitis models
- Superoxide dismutase (SOD) producing GM L.fermentum increased SOD activity by almost eightfold compared to the wild type
- GM Lact. fermentum furthermore showed a higher survival rate and lower disease activity index (P <0·05) in colitis models
- GM L.lactis improved gut microbial composition and GM S.cerevisiae improved microbial diversity whilst reducing the Firmicutes to Bacteroides ratio
- GM E.coli significantly reduced weight loss, colon shortening plus lower disease activity and histological changes (P < 0.05).
Conclusion
Despite the heterogeneity of the trials, GM probiotics appear to play a notable part in ameliorating IBD symptomatology and disease severity when compared to wild-type probiotics. Human efficacy and potential adverse effects require more in-depth trials to ascertain safety and optimal dosages.
Clinical practice applications:
- Probiotics species used in the trials included S.thermophilus, E.coli, L.lactis, B.ovatus, S.boulardii, L.fermentum, B.longhum, L.casei, L.plantarum, and S.cerevisiae. Wild-types of some of these are already available to use in clinical practice
- Note that oral administration in the human trial showed no significant health outcome, therefore efficacy and safety need to be ascertained on an individual patient level
- Colonisation of beneficial bacteria in the gut of IBD patients might be difficult and any form of supplementation therefore needs to be closely monitored.
Considerations for future research:
- More evidence is needed to demonstrate that GM probiotic formulations result in significantly improved outcomes when compared to wild-types
- Future randomised placebo-controlled trials need to include larger cohorts to determine supplement efficacy
- Longer periods of intervention are needed to confirm efficacy, safety, and tolerance for both Crohn’s Disease and Colitis
- Optimal GM probiotic formulation, doses, and means of application need to be identified.
Abstract
BACKGROUND Many preclinical studies have demonstrated the effectiveness of genetically modified probiotics (gm probiotics) in animal models of inflammatory bowel disease (IBD). OBJECTIVE This systematic review was performed to investigate the role of gm probiotics in treating IBD and to clarify the involved mechanisms. METHODS PubMed, Web of Science, Cochrane Library, and Medline were searched from their inception to 18 September 2022 to identify preclinical and clinical studies exploring the efficacy of gm probiotics in IBD animal models or IBD patients. Two independent researchers extracted data from the included studies, and the data were pooled by the type of study; that is, preclinical or clinical. RESULTS Forty-five preclinical studies were included. In these studies, sodium dextran sulfate and trinitrobenzene sulfonic acid were used to induce colitis. Eleven probiotic species have been genetically modified to produce therapeutic substances, including IL-10, antimicrobial peptides, antioxidant enzymes, and short-chain fatty acids, with potential therapeutic properties against colitis. The results showed generally positive effects of gm probiotics in reducing disease activity and ameliorating intestinal damage in IBD models; however, the efficacy of gm probiotics compared to that of wild-type probiotics in many studies was unclear. The main mechanisms identified include modulation of the diversity and composition of the gut microbiota, production of regulatory metabolites by beneficial bacteria, reduction of the pro- to anti-inflammatory cytokine ratio in colonic tissue and plasma, modulation of oxidative stress activity in the colon, and improvement of intestinal barrier integrity. Moreover, only one clinical trial with 10 patients with Crohn's disease was included, which showed that L. lactis producing IL-10 was safe, and a decrease in disease activity was observed in these patients. CONCLUSIONS Gm probiotics have a certain efficacy in colitis models through several mechanisms. However, given the scarcity of clinical trials, it is important for researchers to pay more attention to gm probiotics that are more effective and safer than wild-type probiotics to facilitate further clinical translation.
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B-vitamins, related vitamers, and metabolites in patients with quiescent inflammatory bowel disease and chronic fatigue treated with high dose oral thiamine.
Bager, P, Hvas, CL, Hansen, MM, Ueland, P, Dahlerup, JF
Molecular medicine (Cambridge, Mass.). 2023;29(1):143
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IBD is characterised by chronic inflammation of the gastrointestinal tract with periodic inactive (quiescent disease) and periodic active inflammation. Chronic fatigue is regarded as elevated fatigue levels with duration of more than 6 months. Malnutrition in patients with IBD is well known and this study assessed changes in B-vitamins and their related metabolites directly after high dose oral thiamine, vitamin B1. 40 adult patients with quiescent IBD and chronic fatigue were randomised compared to a control group of 20 patients without fatigue. In total, 52 females and 8 men took part in the trial. Half of the patients had Crohn’s disease and half had ulcerative colitis. Blood samples were taken and patients answered questionnaires regarding fatigue at each study visit. The researchers found low levels of Flavin mononucleotide (FMN), a biomolecule produced from riboflavin (vitamin B2) in patients with chronic fatigue in comparison to patients without fatigue. The researchers also observed that fatigued IBD patients had a less diverse microbiome with reduced numbers of butyrate-producing bacterial species compared to non-fatigued patients, highlighting the importance of vitamin B1 for the growth of gut bacteria. The oral dose of vitamin B1 administered is unclear and other factors influencing fatigue such as diet, sleep and physical activity were not investigated. The researchers conclude the mechanisms of B-vitamins in IBD in relation to fatigue does require further exploration along with assessing vitamin B2’s effect on IBD fatigue.
Abstract
BACKGROUND High doses of oral thiamine improve clinical fatigue scores in patients with quiescent inflammatory bowel disease (IBD) and chronic fatigue. In this study we analysed plasma samples obtained in a randomised clinical trial and aimed compare levels of vitamins B1, B2, B3 and B6, and their related vitamers and metabolites in patients with IBD, with or without chronic fatigue and with or without effect of high dose oral thiamine for chronic fatigue. METHODS Blood samples from patients with fatigue were drawn prior and after thiamine exposure and only once for patients without fatigue. A wide panel of analysis were done at Bevital AS Lab. RESULTS Concentration of flavin mononucleotide (FMN) was lower in patients with chronic fatigue compared to patients without fatigue (p = 0.02). Patients with chronic fatigue who reported a positive effect on fatigue after 4 weeks of high dose thiamine treatment had a statistically significantly lower level of riboflavin after thiamine treatment (p = 0.01). CONCLUSION FMN and Riboflavin were associated with chronic fatigue in patients with quiescent IBD. Levels of other B vitamins and metabolites were not significantly different between the investigated groups or related to effect of the thiamine intervention. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov study identifier NCT036347359. Registered 15 August 2018, https://clinicaltrials.gov/study/NCT03634735?cond=Inflammatory%20Bowel%20Diseases&intr=Thiamine&rank=1.
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Functional response to a microbial synbiotic in the gastrointestinal system of children: a randomized clinical trial.
Tierney, BT, Versalovic, J, Fasano, A, Petrosino, JF, Chumpitazi, BP, Mayer, EA, Boetes, J, Smits, G, Parkar, SG, Voreades, N, et al
Pediatric research. 2023;93(7):2005-2013
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The composition of the human gut microbiome has been identified as playing a role in regulating bowel movements in children. This includes functional constipation, which is characterised by infrequent bowel movements and associated phenotypes such as stool consistency, pain when defecating and bloating. The aim of this study was to determine the impact of a nine-strain (eight species) synbiotic (a prebiotic and defined microbial consortium) formulation (with the prebiotic comprising mixed-chain length oligosaccharides) on ameliorating constipation. This study was a multicentre, randomised, double-blind, and placebo-controlled with two parallel arms. Ninety-one healthy male/female subjects were recruited and randomly assigned to one of the two arms; treatment or placebo group. Results showed that: - compared to placebo, synbiotic use increased weekly bowel movements (WBMs) in constipated children. - there was an increased abundance of the administered probiotic species (bifidobacteria) in the treatment arm. - baseline microbial richness demonstrated potential as a predictive biomarker for response to intervention. Authors conclude that a synbiotic formulation may increase weekly WBMs in children who have low-frequency WBMs.
Abstract
BACKGROUND Oral microbial therapy has been studied as an intervention for a range of gastrointestinal disorders. Though research suggests that microbial exposure may affect the gastrointestinal system, motility, and host immunity in a pediatric population, data have been inconsistent, with most prior studies being in neither a randomized nor placebo-controlled setting. The aim of this randomized, placebo-controlled study was to evaluate the efficacy of a synbiotic on increasing weekly bowel movements (WBMs) in constipated children. METHODS Sixty-four children (3-17 years of age) were randomized to receive a synbiotic (n = 33) comprising mixed-chain length oligosaccharides and nine microbial strains, or placebo (n = 31) for 84 days. Stool microbiota was analyzed on samples collected at baseline and completion. The primary outcome was a change from baseline of WBMs in the treatment group compared to placebo. RESULTS Treatment increased (p < 0.05) the number of WBMs in children with low baseline WBMs, despite broadly distinctive baseline microbiome signatures. Sequencing revealed that low baseline microbial richness in the treatment group significantly anticipated improvements in constipation (p = 0.00074). CONCLUSIONS These findings suggest the potential for (i) multi-species-synbiotic interventions to improve digestive health in a pediatric population and (ii) bioinformatics-based methods to predict response to microbial interventions in children. IMPACT Synbiotic microbial treatment improved the number of spontaneous weekly bowel movements in children compared to placebo. Intervention induced an increased abundance of bifidobacteria in children, compared to placebo. All administered probiotic species were enriched in the gut microbiome of the intervention group compared to placebo. Baseline microbial richness demonstrated potential as a predictive biomarker for response to intervention.
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Effects of a Raisin Supplement on Cognitive Performance, Quality of Life, and Functional Activities in Healthy Older Adults-Randomized Clinical Trial.
Rodrigo-Gonzalo, MJ, González-Manzano, S, Pablos-Hernández, MC, Méndez-Sánchez, R, Ayuda Duran, B, González-Sánchez, J, Barbero-Iglesias, F, González-Paramás, AM, Recio-Rodríguez, JI
Nutrients. 2023;15(12)
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The regular intake of foods rich in polyphenols shows many biological activities, such as antioxidant, cardioprotective, anti-inflammation and anti-aging properties. This diversity of compounds found in grapes, especially red grapes, makes it a candidate for testing the role of dietary polyphenols to health. The objective of this single blinded randomised controlled clinical trial was to evaluate the effects of consuming 50g of Málaga muscatel raisins which are dried grapes on cognitive performance, quality of life, and functional activities in healthy adults over 70 years. According to the researchers this is the first study looking at the effect of raisins on cognitive performance. A group of 80 participants were split into two groups with one group adding 50g of raisins a day to their usual diet for six months and a control group of 40 patients receiving no raisins. Cognitive performance was measured by various tests which are summarised in the full text article. The results of this study showed that the supplement of 50 g of raisins slightly improved cognitive performance including spatial orientation, memory and comprehension, reading, writing, and drawing. In addition to a slight improvement in quality of life and functional activities. This shows promising results and that the addition of raisins to the diet along with a variety of foods rich in polyphenols can confer positive health benefits that can prevent age related cognitive decline. More research is needed to know exactly the mechanism of action of polyphenols on cognitive performance.
Abstract
The objective of this study was to evaluate the effects of consuming 50 g of raisins on cognitive performance, quality of life, and functional activities in healthy older adults. This is a parallel randomized controlled clinical trial, in which 80 subjects over 70 years of age participated. For 6 months, the intervention group (IG; n = 40) consumed 50 g of raisins per day added to their usual diet, whereas the control group (CG; n = 40) received no supplement. All variables were measured at baseline and at 6 months. Cognitive performance assessed with the Montreal Cognitive Assessment (MOCA) test shows a difference of 3.27 points (95% CI 1.59 to 4.96), p ≤ 0.001, favorable to the IG, after the intervention. Among the cognitive performances, an improvement is observed in the IG in orientation, assessed both with the MOCA test 0.49 (95% CI 0.10 to 0.87), p = 0.014, and with the Mini-Mental State Examination (MMSE) test, 0.36 (95% CI 0.02 to 0.70), p = 0.038. In visuospatial/executive capacity and in language, improvements were also observed in the IG, 1.36 (95% CI 0.77 to 1.95), p = 0.001, and 0.54 points (95% CI 0.12 to 0.96), p = 0.014, respectively. Immediate and delayed recall, assessed with the Rey Auditory Verbal Learning Test, improved in the IG. In addition, the IG showed a better quality of life and greater autonomy in instrumental activities of daily living after 6 months. No significant changes were observed in the rest of the variables analyzed. Therefore, the consumption of 50 g of raisins produces a slight improvement in cognitive performance, quality of life, and functional activities in the elderly.
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Acute beetroot juice reduces blood pressure in young Black and White males but not females.
Grosicki, GJ, Flatt, AA, Cross, BL, Vondrasek, JD, Blumenburg, WT, Lincoln, ZR, Chall, A, Bryan, A, Patel, RP, Ricart, K, et al
Redox biology. 2023;63:102718
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Cardiovascular (CV) disease is the leading cause of death in the United States. Out of all ethnic groups, CV disease is particularly common in black Americans. High blood pressure (BP) is one of the main contributors to CV disease, and black Americans exhibit a disproportionally higher incident rate of high BP when compared to other ethnic groups. Partly this is due to genetic and physiological differences, yet is also influenced by social, socioeconomic, and environmental factors. One physiological difference that may contribute to higher BP in black adults appears to be a reduced availability of nitric oxide (NO). NO is a gas that is abundant in the human body. It regulates vascular tone and elasticity of the arteries, and therefore helps to manage blood pressure. Nitrates that occur in foods can be converted to NO and thus contribute to NO levels in the body. Beetroot juice (BRJ) is rich in nitrates. This study examined whether BRJ supplementation can reduce resting BP and cardiovascular reactivity in adults. The randomized, placebo-controlled, crossover-design study was completed by 18 black and 20 white young adults, male and female, with an average age of 21. The study monitored heart rate, BP and arterial stiffness in a variety of settings. The study also assessed socioeconomic status, perceived discrimination, sleep and dietary intake. The main findings from this investigation were that despite young black adults having higher resting BP, acute BRJ supplementation reduced the pressure to a similar extent in young black and white adults, but primarily in males. This reduction correlated with increased levels of circulating nitrites. However, acute BRJ supplementation did not influence resting arterial stiffness. The result also highlighted previously seen racial differences relating to social determinants of health and lifestyle, which may contribute to the elevated BP values seen in black participants. The study demonstrated that dietary nitrate from beetroot juice has the potential to be a cost-effective blood pressure-lowering strategy for young black and white males. Yet the findings also highlighted the complex interplay of social, lifestyle, and underlying physiological factors that influence racial differences when it comes to CV health
Abstract
A complex interplay of social, lifestyle, and physiological factors contribute to Black Americans having the highest blood pressure (BP) in America. One potential contributor to Black adult's higher BP may be reduced nitric oxide (NO) bioavailability. Therefore, we sought to determine whether augmenting NO bioavailability with acute beetroot juice (BRJ) supplementation would reduce resting BP and cardiovascular reactivity in Black and White adults, but to a greater extent in Black adults. A total of 18 Black and 20 White (∼equal split by biological sex) young adults completed this randomized, placebo-controlled (nitrate (NO3-)-depleted BRJ), crossover design study. We measured heart rate, brachial and central BP, and arterial stiffness (via pulse wave velocity) at rest, during handgrip exercise, and during post-exercise circulatory occlusion. Compared with White adults, Black adults exhibited higher pre-supplementation resting brachial and central BP (Ps ≤0.035; e.g., brachial systolic BP: 116(11) vs. 121(7) mmHg, P = 0.023). Compared with placebo, BRJ (∼12.8 mmol NO3-) reduced resting brachial systolic BP similarly in Black (Δ-4±10 mmHg) and White (Δ-4±7 mmHg) adults (P = 0.029). However, BRJ supplementation reduced BP in males (Ps ≤ 0.020) but not females (Ps ≥ 0.299). Irrespective of race or sex, increases in plasma NO3- were associated with reduced brachial systolic BP (ρ = -0.237, P = 0.042). No other treatment effects were observed for BP or arterial stiffness at rest or during physical stress (i.e., reactivity); Ps ≥ 0.075. Despite young Black adults having higher resting BP, acute BRJ supplementation reduced systolic BP in young Black and White adults by a similar magnitude, an effect that was driven by males.
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Influence of methyl donor nutrients as epigenetic regulators in colorectal cancer: A systematic review of observational studies.
Chávez-Hidalgo, LP, Martín-Fernández-de-Labastida, S, M de Pancorbo, M, Arroyo-Izaga, M
World journal of gastroenterology. 2023;29(7):1219-1234
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Colorectal cancer (CRC) is the third most frequent type of cancer and yet has the second highest mortality rate in cancer patients worldwide. Hence there is an urgency to understand more about dietary and lifestyle factors that can help to prevent this type of cancer. It is known that folate has a preventive function in CRC, possibly due to its role in DNA methylation. Methylation is the addition of methyl groups to DNA, which influences gene expression and regulation. This systematic review investigated how folate and other dietary methyl groups and methyl influencers such as B vitamins and alcohol influence the development of CRC, whilst also considering various genetic variants in methyl-metabolising enzymes (polymorphisms). The analysis included a total of 19 case-control and cohort studies and highlighted that potential interactions between methyl donor nutrients, genetic variants, and alcohol influence CRC risk. For most, high levels of folate intake were considered a protective factor, while high alcohol consumption proved to be a risk factor. Yet these interactions appear to be complex, with gender, genetic variations and folate status appearing to contribute to variable and, in some cases, contradictory outcomes. The authors suggested in their findings that Vitamin B6, Vitamin B3 (Niacin), and alcohol may affect CRC by influencing its risk by acting on both the genetic code itself and the epigenetic factors that control gene activity. Further research is needed to better understand the complexity of these mechanisms, and to help clarify the influence of methyl group donors as epigenetic regulators of gene activity in CRC development.
Abstract
BACKGROUND Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer (CRC). However, whether the influence of methyl donor intake is modified by polymorphisms in such epigenetic regulators is still unclear. AIM: To improve the current understanding of the molecular basis of CRC. METHODS A literature search in the Medline database, Reference Citation Analysis (https:// www.referencecitationanalysis.com/), and manual reference screening were performed to identify observational studies published from inception to May 2022. RESULTS A total of fourteen case-control studies and five cohort studies were identified. These studies included information on dietary methyl donors, dietary components that potentially modulate the bioavailability of methyl groups, genetic variants of methyl metabolizing enzymes, and/or markers of CpG island methylator phenotype and/or microsatellite instability, and their possible interactions on CRC risk. CONCLUSION Several studies have suggested interactions between methylenetetrahydrofolate reductase polymorphisms, methyl donor nutrients (such as folate) and alcohol on CRC risk. Moreover, vitamin B6, niacin, and alcohol may affect CRC risk through not only genetic but also epigenetic regulation. Identification of specific mechanisms in these interactions associated with CRC may assist in developing targeted prevention strategies for individuals at the highest risk of developing CRC.
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Effect of vitamin E on Semen Quality Parameters: A Meta-Analysis of a Randomized Controlled Trial.
Wang, R, Wang, S, Song, Y, Zhou, H, Pan, Y, Liu, L, Niu, S, Liu, X
Urology journal. 2022;19(5):343-351
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The incidence of male infertility is increasing year by year. The mechanism of male infertility is complex. One of the important causes of male infertility is the decline in semen quality. The aim of this study was to evaluate the effectiveness of oral vitamin E in improving semen quality. This study is a meta-analysis of eight articles with a total of 459 patients, including 238 cases in the experimental group and 221 cases in the control group. Results show that oral vitamin E treatment could significantly increase the total sperm count and reduce the volume of semen. It was further found that oral vitamin E treatment for up to 6 months could improve the forward motility of sperm but not for 3 months. Authors conclude that vitamin E could increase the total sperm count and reduce the volume of semen in male infertility patients.
Abstract
PURPOSE To explore the effectiveness of vitamin E in male infertility, a systematic review and meta-analysis was conducted. MATERIALS AND METHODS The retrieval time was from January 1947 to May 2021, without language restriction. Stata 12.0 was used for the meta-analysis. RESULTS A total of 8 randomized controlled trials involving 459 patients were included. The results showed that after vitamin E treatment, semen volume was reduced (95% CI: - 0.55 to - 0.06, SMD = - 0.30, p = 0.015), total sperm count was increased (95% CI: 0.02-0.45, SMD = 0.23, p = 0.035), and the differences were statistically significant. There were no statistically significant differences in increasing sperm concentration (95% CI: -0.21-0.29, SMD = 0.04, p = 0.769), total sperm motility (95% CI: -0.01-0.42, SMD = 0.20, p = 0.061) or sperm forward motility rate (95% CI: -0.06-0.65, SMD = 0.29, p = 0.106). Subgroup analysis showed that vitamin E treatment for six months could improve sperm forward motility (95% CI: 0.46-1.14, SMD = 0.80, p <0.001). CONCLUSION Vitamin E could increase the total sperm count and reduce the volume of semen in male infertility patients, and long-term treatment could improve the forward motility rate of sperm. The decrease of semen volume may be the result of different abstinence time before and after the test.
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Dietary macronutrients and the gut microbiome: a precision nutrition approach to improve cardiometabolic health.
Jardon, KM, Canfora, EE, Goossens, GH, Blaak, EE
Gut. 2022;71(6):1214-1226
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The global rise in the prevalence of obesity is strongly associated with an increase in the incidence and prevalence of cardiometabolic diseases, including insulin resistance (IR) and type 2 diabetes mellitus. In recent years, advancements have been made in understanding the involvement of the gut microbiome in obesity and related cardiometabolic complications as regulator of host energy and substrate metabolism. This study is a review that discusses the latest research describing interactions between dietary composition, the gut microbiome and host metabolism. Results show that current evidence for developing optimal dietary interventions targeting bodyweight control and IR via the gut microbiota is still in its infancy and does not capture the complexity of the integration of a whole-diet approach, the microbial and the host’s metabolic phenotype. Furthermore, implementation of targeted, precision nutrition intervention strategies or dietary guidelines for individuals or subgroups in public health requires further insight in the mechanisms involved in (non-)response to dietary intervention. Authors conclude that future studies are needed and these should focus on assessing detailed individual phenotyping and gaining insight into the balance between carbohydrate and protein fermentation by the gut microbiota as well as the site of fermentation in the colon.
Abstract
Accumulating evidence indicates that the gut microbiome is an important regulator of body weight, glucose and lipid metabolism, and inflammatory processes, and may thereby play a key role in the aetiology of obesity, insulin resistance and type 2 diabetes. Interindividual responsiveness to specific dietary interventions may be partially determined by differences in baseline gut microbiota composition and functionality between individuals with distinct metabolic phenotypes. However, the relationship between an individual's diet, gut microbiome and host metabolic phenotype is multidirectional and complex, yielding a challenge for practical implementation of targeted dietary guidelines. In this review, we discuss the latest research describing interactions between dietary composition, the gut microbiome and host metabolism. Furthermore, we describe how this knowledge can be integrated to develop precision-based nutritional strategies to improve bodyweight control and metabolic health in humans. Specifically, we will address that (1) insight in the role of the baseline gut microbial and metabolic phenotype in dietary intervention response may provide leads for precision-based nutritional strategies; that (2) the balance between carbohydrate and protein fermentation by the gut microbiota, as well as the site of fermentation in the colon, seems important determinants of host metabolism; and that (3) 'big data', including multiple omics and advanced modelling, are of undeniable importance in predicting (non-)response to dietary interventions. Clearly, detailed metabolic and microbial phenotyping in humans is necessary to better understand the link between diet, the gut microbiome and host metabolism, which is required to develop targeted dietary strategies and guidelines for different subgroups of the population.
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Serum vitamin E levels and chronic inflammatory skin diseases: A systematic review and meta-analysis.
Liu, X, Yang, G, Luo, M, Lan, Q, Shi, X, Deng, H, Wang, N, Xu, X, Zhang, C
PloS one. 2021;16(12):e0261259
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Vitiligo, Psoriasis, Acne and Atopic Dermatitis are chronic immune-mediated inflammatory skin conditions characterised by itchy skin. In previous studies, decreased serum vitamin E levels have been associated with an increased risk of skin diseases. Nuts, oils from plants, and vegetables contain vitamin E, which is a dietary bioactive compound that has anti-inflammatory and antioxidant properties. In this systematic review and meta-analysis, twenty case-controlled studies were included, of which thirteen specifically examined alpha-tocopherol levels. Psoriasis, Vitiligo, atopic dermatitis, and acne patient groups had significantly lower levels of serum Vitamin E than the control groups. There is no clear understanding of the pathogenesis of chronic inflammatory skin conditions. One of the underlying mechanisms is the interaction between oxidative stress and the immune system, as well as the accumulation of free radicals in the epidermal layers of the skin. As there is limited evidence regarding the benefits of Vitamin E in improving chronic inflammatory skin conditions, further robust studies are necessary. Healthcare professionals can use this research to gain a better understanding of the potential clinical applications of vitamin E in the treatment of skin disorders.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Low serum vitamin E levels are reported to be associated with several chronic inflammatory skin diseases, such as vitiligo, psoriasis, atopic dermatitis, and acne.
- Practitioners could consider vitamin E therapy in those with low serum concentrations
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
This systematic review and meta-analysis report on the association between serum vitamin E levels and chronic inflammatory skin diseases.
The review which followed PRISMA reporting guidelines, screened 892 studies. After the selection and exclusions, 20 case-control studies were included involving a total of 1172 patients.
The studies that were included focused mainly on chronic inflammatory diseases, including vitiligo, psoriasis, atopic dermatitis, and acne. Eight studies included only adults, five included only children or teenagers and six studies included adults and children. One study had no age description.
Thirteen studies stated that alpha-tocopherol was used in their investigations. However, seven studies did not describe the subunit of vitamin E.
Primary clinical outcomes were:
- Seven studies, with 351 cases and 350 controls reported that compared with the control group, vitiligo patients had lower serum vitamin E concentrations (Standard Mean Difference (SMD):0.70, 95% Cl:121-0.19.
- Six studies investigated the change of serum vitamin E levels in patients with psoriasis, with 278 cases and 257 controls. Compared with the control group, psoriasis patients had lower serum vitamin E concentrations (SMD: -2.37, 95% CI: -3.57 to -1.18).
- The serum vitamin E Levels in patients with atopic dermatitis were observed in 4 studies, with 259 cases and 307 controls. Compared with the control group atopic dermatitis patients had lower serum vitamin E concentrations (SMD: -1.08, 95% CI: -1.80 to -0.36).
Levels of serum vitamin E in acne patients were reported in 3 studies, with 284 cases and 186 controls. Compared with the control group, acne patients had lower serum concentration levels of vitamin E (SMD: -0.67, 95% CI: -1.05 to -0.30).
No publication bias was found in any association (Egger’s test >0.05), though heterogeneity was considerable in every case (I2 > 80%), though this interaction was not significant for acne (p=0.879). Associations were not split by age, or any other cofactor, however sensitivity analyses did not indicate modification of the results.
The authors also assessed the association between skin disease severity and serum vitamin E concentrations. Overall, more severe disease was associated with a lower serum vitamin E concentration (SMD -1.56, 95% CI:-2.53 to -059).
Clinical practice applications:
- Vitamin E has gained the attention of researchers as a potential adjuvant therapy for various skin disorders due to its excellent antioxidant and anti-inflammatory properties.
- This review reports on the low levels of serum vitamin E found in patients with vitiligo, psoriasis, atopic dermatitis, and acne, and also suggests that serum concentrations of vitamin E are lower in those with more severe disease. Based on these findings, practitioners could therefore consider investigating the serum vitamin E levels of patients with inflammatory skin diseases and consider including vitamin E in their treatment protocols if their serum vitamin E levels are low.
Considerations for future research:
- The small number of studies in this review indicates the need for further research to be done on vitamin E and inflammatory skin diseases.
- Although there are reports on the antioxidant and anti-inflammatory properties of vitamin E, further investigations are needed to determine the exact mechanism of action in inflammatory skin diseases.
- Additionally, further investigation is needed to evaluate which chemical forms of vitamin E and their dosage amounts have beneficial effects on inflammatory skin diseases.
Abstract
BACKGROUND Vitamin E has long been linked to skin health, including all of its possible functions in cosmetic products, to its roles in membrane integrity and even the aging process. However, reports on the relationship between serum vitamin E levels and the risk of chronic inflammatory skin diseases have been inconsistent. We performed a systematic review and meta-analysis to evaluate the association between serum vitamin E levels and chronic inflammatory skin diseases. METHODS We searched the PubMed, Web of Science and Scopus databases, with no time limit up to 30.06.2021. Studies examining serum vitamin E levels in patients with chronic inflammatory skin diseases were selected. RESULTS Twenty articles met the inclusion criteria. Compared with controls, a lower vitamin E level was found in patients with vitiligo (SMD: -0.70, 95% CI: -1.21 to -0.19), psoriasis (SMD: -2.73, 95% CI: -3.57 to -1.18), atopic dermatitis (SMD: -1.08, 95% CI: -1.80 to -0.36) and acne (SMD: -0.67, 95% CI: -1.05 to -0.30). CONCLUSIONS Our meta-analysis showed that serum vitamin E levels were lower in patients suffering from vitiligo, psoriasis, atopic dermatitis and acne. This study highlights the need to evaluate vitamin E status to improve its level in patients with skin diseases.
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10.
Nutrition in Menopausal Women: A Narrative Review.
Silva, TR, Oppermann, K, Reis, FM, Spritzer, PM
Nutrients. 2021;13(7)
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Plain language summary
Menopause is the permanent cessation of menstrual cycles following the loss of ovarian follicular activity. It is associated with increased prevalence of obesity, metabolic syndrome, cardiovascular disease, and osteoporosis. The aim of this narrative review was to discuss the current evidence on the association between dietary patterns and clinical endpoints in postmenopausal women (body composition, bone mass, and risk markers for cardiovascular disease), and thereby providing novel insight into the establishment of optimal dietary guidelines for healthy postmenopausal period. Research shows that: - the changes in weight and fat distribution in women are associated with aging and mainly with the decrease in oestradiol levels during peri- and post-menopause. - calcium, vitamin D, vitamin K, selenium, magnesium, and beta-carotene adequate intake could be linked with better BMD in postmenopausal women. - diet is a major modifiable risk factor for cardiovascular disease and could be a powerful intervention to reduce cardiovascular risks in postmenopausal women. - the Mediterranean diet is composed of healthy foods that have anti-inflammatory and antioxidant properties. Authors indicate that future studies evaluating the effects of low-fat, plant-based diets on fat mass in post-menopausal women are needed.
Abstract
Among the various aspects of health promotion and lifestyle adaptation to the postmenopausal period, nutritional habits are essential because they concern all women, can be modified, and impact both longevity and quality of life. In this narrative review, we discuss the current evidence on the association between dietary patterns and clinical endpoints in postmenopausal women, such as body composition, bone mass, and risk markers for cardiovascular disease. Current evidence suggests that low-fat, plant-based diets are associated with beneficial effects on body composition, but further studies are needed to confirm these results in postmenopausal women. The Mediterranean diet pattern along with other healthy habits may help the primary prevention of bone, metabolic, and cardiovascular diseases in the postmenopausal period. It consists on the use of healthy foods that have anti-inflammatory and antioxidant properties, and is associated with a small but significant decrease in blood pressure, reduction of fat mass, and improvement in cholesterol levels. These effects remain to be evaluated over a longer period of time, with the assessment of hard outcomes such as bone fractures, diabetes, and coronary ischemia.