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Sunday, April 16, 2017

Health implications of the influence of diet on the gut microbiome


Abstract (as presented by the authors of the scientific work):

"Recent studies have suggested that the intestinal microbiome plays an important role in modulating risk of several chronic diseases, including inflammatory bowel disease, obesity, type 2 diabetes, cardiovascular disease, and cancer. At the same time, it is now understood that diet plays a significant role in shaping the microbiome, with experiments showing that dietary alterations can induce large, temporary microbial shifts within 24 h. Given this association, there may be significant therapeutic utility in altering microbial composition through diet. This review systematically evaluates current data regarding the effects of several common dietary components on intestinal microbiota. We show that consumption of particular types of food produces predictable shifts in existing host bacterial genera. Furthermore, the identity of these bacteria affects host immune and metabolic parameters, with broad implications for human health. Familiarity with these associations will be of tremendous use to the practitioner as well as the patient."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Conclusion and future directions (as presented by the authors of the scientific work):

"In conclusion, review of the literature suggests that diet can modify the intestinal microbiome, which in turn has a profound impact on overall health. This impact can be beneficial or detrimental, depending on the relative identity and abundance of constituent bacterial populations. For example, it has been shown that a high-fat diet adversely reduces A. muciniphila and Lactobacillus, which are both associated with healthy metabolic states [53]. This observation provides a good example of how dietary intervention might potentially be used to manage complex diseases, such as obesity and diabetes. Furthermore, advances in microbiome research have suggested novel therapeutic possibilities for diseases that have traditionally been difficult to treat. For example, the fecal microbiota transplant has been used successfully to manage several different conditions, including ulcerative colitis, Clostridium difficile-associated colitis, irritable bowel syndrome, and even obesity [156–160]. It is possible that dermatologic conditions, including psoriasis and atopic dermatitis, may also be observed to benefit from re-engineering the gut microbiota. Recent advances in microbiome research offer exciting new tools to possibly enhance human health. Most of the studies reviewed in this manuscript profiled the microbiome using 16S rRNA amplicon sequencing, which utilizes the hypervariable regions of the bacterial 16S rRNA gene to identify bacteria present in biological samples. 16S rRNA sequencing is the most commonly used method by medical researchers to study microbial composition, due to its low cost and relatively easy workflow for sample preparation and bioinformatic analyses. However, 16S rRNA amplicon sequencing primarily provides information about microbial identity and not function. In order to investigate the microbiome’s functions, many researchers have turned to a shotgun metagenomic approach in which the whole bacterial genome is sequenced. Despite a higher cost and more complicated bioinformatics requirement, shotgun metagenomics provides information about both microbial identity and gene composition. Knowing which genes are encoded by the bacteria present in a sample allows researchers to better understand their roles in human health. With reducing costs of next generation sequencing, improved sample preparation protocols, and more bioinformatic tools available for metagenomic analysis, this technique will be a powerful tool to study microbiome functionality. Performing meta-analyses to correlate the microbiome with host genomes, transcriptomes, and immunophenotypes represents another exciting avenue for investigating human and bacterial interactions.

Precision medicine is another attractive, novel therapeutic approach for many diseases with strong genetic associations. It is important to note that the host genotype also plays a role in shaping the microbiome, and that this host-microbe interaction is crucial for maintaining human health [161]. Therefore, a better understanding of the interplay between genes, phenotypes, and the microbiome will provide important insights into the utility of precision medicine.

The observation that diet can modulate host-microbe interactions heralds a promising future therapeutic approach. Already, the gut microbiome has been found to influence the response to cancer immunotherapy [162, 163]. Indeed, personalized nutrition is an emerging concept that utilizes a machine-learning algorithm to predict metabolic responses to meals [164, 165]. This tool has broad implications for individualized patient care through dietary modification. While this and other technology is in the process of being refined and validated, further research using large, long-term clinical trials to evaluate a greater variety of food components would be helpful in making specific dietary recommendations to patients."


Full-text access of the referenced scientific work:

Singh RK, Chang HW, Yan D, Lee KM, Ucmak D, Wong K, Abrouk M, Farahnik B,
Nakamura M, Zhu TH, Bhutani T, Liao W. Influence of diet on the gut microbiome
and implications for human health. J Transl Med. 2017 Apr 8;15(1):73. doi:
10.1186/s12967-017-1175-y. Review. PubMed PMID: 28388917; PubMed Central PMCID:
PMC5385025.
https://www.researchgate.net/publication/315978151_Influence_of_diet_on_the_gut_microbiome_and_implications_for_human_health


Webmaster:

Prof. Atanas G. Atanasov (Dr. habil., PhD)
https://about.me/Atanas_At


Monday, April 10, 2017

Inflammation regulation by short chain fatty acids


Abstract (as presented by the authors of the scientific work):

"The short chain fatty acids (SCFAs) acetate (C(2)), propionate (C(3)) and butyrate (C(4)) are the main metabolic products of anaerobic bacteria fermentation in the intestine. In addition to their important role as fuel for intestinal epithelial cells, SCFAs modulate different processes in the gastrointestinal (GI) tract such as electrolyte and water absorption. These fatty acids have been recognized as potential mediators involved in the effects of gut microbiota on intestinal immune function. SCFAs act on leukocytes and endothelial cells through at least two mechanisms: activation of GPCRs (GPR41 and GPR43) and inhibiton of histone deacetylase (HDAC). SCFAs regulate several leukocyte functions including production of cytokines (TNF-α, IL-2, IL-6 and IL-10), eicosanoids and chemokines (e.g., MCP-1 and CINC-2). The ability of leukocytes to migrate to the foci of inflammation and to destroy microbial pathogens also seems to be affected by the SCFAs. In this review, the latest research that describes how SCFAs regulate the inflammatory process is presented. The effects of these fatty acids on isolated cells (leukocytes, endothelial and intestinal epithelial cells) and, particularly, on the recruitment and activation of leukocytes are discussed. Therapeutic application of these fatty acids for the treatment of inflammatory pathologies is also highlighted."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Conclusions (as presented by the authors of the scientific work):

"SCFAs present multiple effects in different cells involved in the inflammatory and immune responses. These fatty acids not only affect the function of leukocytes (e.g., production of inflammatory mediators and ability of leukocytes to migrate) but can also induce apoptosis in lymphocytes [96,97], macrophages [98] and neutrophils [99]. The latter effect may be relevant for the outcome of the inflammatory process and the immune response to bacteria that produce these fatty acids.

In general, SCFAs, such as propionate and butyrate, inhibit stimuli-induced expression of adhesion molecules, chemokine production and consequently suppress monocyte/macrophage and neutrophil recruitment, suggesting an anti-inflammatory action. However, there is also evidence in favor of a pro-inflammatory action of SCFAs in some conditions [20,100]. This discrepancy may be in part explained by the ability of SCFAs to induce neutrophil migration. In sites of anaerobic bacteria infection or after loss of intestinal epithelial integrity, high concentrations of SCFAs may lead to neutrophil accumulation and amplification of the inflammatory process. Another possible explanation is the fact that these fatty acids may present divergent effects depending on the cell type (e.g., anti- and pro-inflammatory effects of SCFAs on macrophage and microglial cells have been demonstrated [52,97,101]). Therefore, although SCFAs modulate the function of immune cells, more studies are necessary in order to understand the precise role of SCFAs on the interaction between bacteria and host immune cells in vivo, particularly in the GI tract and in sites of anaerobic infections including the skin, oral cavity and respiratory tract."


Full-text access of the referenced scientific work:

Vinolo MA, Rodrigues HG, Nachbar RT, Curi R. Regulation of inflammation by
short chain fatty acids. Nutrients. 2011 Oct;3(10):858-76. doi:
10.3390/nu3100858. Epub 2011 Oct 14. Review. PubMed PMID: 22254083; PubMed
Central PMCID: PMC3257741.
https://www.researchgate.net/publication/221755956_Regulation_of_Inflammation_by_Short_Chain_Fatty_Acids


Webmaster:

Prof. Atanas G. Atanasov (Dr. habil., PhD)
https://about.me/Atanas_At


Saturday, April 8, 2017

Dietary constituents with “exercise mimetic'' action


Abstract (as presented by the authors of the scientific work):

"Endurance exercise, when performed regularly as part of a training program, leads to increases in whole-body and skeletal muscle-specific oxidative capacity. At the cellular level, this adaptive response is manifested by an increased number of oxidative fibers (Type I and IIA myosin heavy chain), an increase in capillarity and an increase in mitochondrial biogenesis. The increase in mitochondrial biogenesis (increased volume and functional capacity) is fundamentally important as it leads to greater rates of oxidative phosphorylation and an improved capacity to utilize fatty acids during sub-maximal exercise. Given the importance of mitochondrial biogenesis for skeletal muscle performance, considerable attention has been given to understanding the molecular cues stimulated by endurance exercise that culminate in this adaptive response. In turn, this research has led to the identification of pharmaceutical compounds and small nutritional bioactive ingredients that appear able to amplify exercise-responsive signaling pathways in skeletal muscle. The aim of this review is to discuss these purported exercise mimetics and bioactive ingredients in the context of mitochondrial biogenesis in skeletal muscle. We will examine proposed modes of action, discuss evidence of application in skeletal muscle in vivo and finally comment on the feasibility of such approaches to support endurance-training applications in humans."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Conclusions (as presented by the authors of the scientific work):

"Endurance exercise is a potent stimulus to induce mitochondrial biogenesis in skeletal muscle (Holloszy, 1967; Molé et al., 1971; Oscai and Holloszy, 1971; Hoppeler et al., 1973; Spina et al., 1996). The nutritional approaches described herein could provide a framework to support endurance training via enhancing mitochondrial biogenesis. In this context, we propose that these small molecules should be viewed as exercise enhancers, not mimetics, as they have minimal effect in basal conditions. In the future, it will be interesting to explore the efficacy of using these nutrients in human studies in vivo, to identify the exercise setting in which they may have the most benefit as well as developing optimal supplementation strategies. In this regard, future studies could examine the effect of bioactives during and in recovery from exercise across a variety of intensities, and also examine supplementation during periods of tapering or detraining to shed light on the practical implications of bioactives as regulators of mitochondrial biogenesis in skeletal muscle. In order to achieve this, researchers should perform randomized, placebo-controlled, intervention trials in human subjects (Hasler, 2002), and examine the extent to which the bioactive ingredient in question is absorbed and bioavailable in skeletal muscle (Crowe et al., 2013). Once achieved, it is hoped that bioactives such as those discussed, and derivatives/associated bioactive ingredients yet to be identified may lead to the next-generation of nutritional supplements to specifically enhance mitochondrial adaptations to endurance training."


Full-text access of the referenced scientific work:

Craig DM, Ashcroft SP, Belew MY, Stocks B, Currell K, Baar K, Philp A.
Utilizing small nutrient compounds as enhancers of exercise-induced mitochondrial
biogenesis. Front Physiol. 2015 Oct 27;6:296. doi: 10.3389/fphys.2015.00296.
eCollection 2015. Review. PubMed PMID: 26578969; PubMed Central PMCID:
PMC4621424.
https://www.researchgate.net/publication/283451923_Utilizing_small_nutrient_compounds_as_enhancers_of_exercise-induced_mitochondrial_biogenesis


Webmaster:

Prof. Atanas G. Atanasov (Dr. habil., PhD)
https://about.me/Atanas_At


Thursday, April 6, 2017

Chronic diseases and aging: potential applications of circadian clock-enhancing small molecules


Abstract (as presented by the authors of the scientific work):

"Normal physiological functions require a robust biological timer called the circadian clock. When clocks are dysregulated, misaligned, or dampened, pathological consequences ensue, leading to chronic diseases and accelerated aging. An emerging research area is the development of clock-targeting compounds that may serve as drug candidates to correct dysregulated rhythms and hence mitigate disease symptoms and age-related decline. In this review, we first present a concise view of the circadian oscillator, physiological networks, and regulatory mechanisms of circadian amplitude. Given a close association of circadian amplitude dampening and disease progression, clock-enhancing small molecules (CEMs) are of particular interest as candidate chronotherapeutics. A recent proof-of-principle study illustrated that the natural polymethoxylated flavonoid nobiletin directly targets the circadian oscillator and elicits robust metabolic improvements in mice. We describe mood disorders and aging as potential therapeutic targets of CEMs. Future studies of CEMs will shed important insight into the regulation and disease relevance of circadian clocks."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Future directions and concluding remarks (as presented by the authors of the scientific work):

"Circadian amplitude regulation and pharmacological modifiers are exciting research topics with promising translational potential. The list of CEMs will likely continue to grow, either from phenotypic screening, as in the case of NOB, or from targeted ligand development (14). On the other hand, pharmacological agents shown to target or mimic clock-enhancing pathways such as CR, TRF, and exercise are a rich venue for discovery of additional clock-targeting agents (63, 130, 161, 170). For example, a growing number of small molecules or drugs have been shown to extend life span and health span, including those deliberately designed to mimic CR and other manipulations (170, 171). Future studies should characterize their circadian clock effects and delineate molecular mechanisms.

Besides metabolic diseases, mood disorders, and aging, other chronic diseases such as neurodegenerative diseases (172, 173) have also been shown to correlate with dampened circadian amplitude or clock dysregulation and may represent new venues for studies of clock modifiers. In addition to antidepressive effects, several studies have shown neurological efficacies of NOB using transgenic disease models (Table ​(Table2).2). For example, 11-day oral administration of NOB resulted in an overall memory improvement in olfactory-bulbectomized (OBX) mice based on the step-through passive-avoidance task and the Y-maze test (111). OBX mice share clinical features with both human neurodegenerative diseases and major depression (174). The depression-like phenotype is thought to derive from pathological or compensatory mechanisms within the cortical–hippocampal–amygdala circuit, which typically involve deterioration of spine density and/or synaptic strength changes (175). Future studies are required to determine the specific role of circadian clocks and RORs in disease models.

Significant gaps of knowledge remain regarding circadian amplitude regulation, especially the mechanisms employed by CEMs. At the intracellular level, questions of particular interest include gene expression regulation, such as cofactor recruitment, epigenetic mechanisms, and chromosome dynamics (1). At the intercellular and system levels, other coupling molecules in addition to VIP and the communication between peripheral and central clocks are outstanding questions (50). It is conceivable that CEMs execute distinct mechanistic schemes to restore a robust overall output under disease or aging conditions. Exemplified by the complex and divergent ROR mechanisms when bound by distinct ligands (74, 90, 91), a detailed mechanistic understanding is important to fully exploit the therapeutic potential of individual CEMs.

In conclusion, circadian clocks safeguard physiological health, and dysregulated and dampened clocks can serve as therapeutic targets to mitigate disease symptoms. Exciting functional and mechanistic studies await to develop CEMs as novel preventive and therapeutic agents."


Full-text access of the referenced scientific work:

Gloston GF, Yoo SH, Chen ZJ. Clock-Enhancing Small Molecules and Potential
Applications in Chronic Diseases and Aging. Front Neurol. 2017 Mar 15;8:100. doi:
10.3389/fneur.2017.00100. eCollection 2017. Review. PubMed PMID: 28360884; PubMed
Central PMCID: PMC5350099.
https://www.researchgate.net/publication/315060004_Clock-Enhancing_Small_Molecules_and_Potential_Applications_in_Chronic_Diseases_and_Aging


Webmaster:

Prof. Atanas G. Atanasov (Dr. habil., PhD)
https://about.me/Atanas_At


Tuesday, April 4, 2017

Avocado: scientific review of possible health benefits


Abstract (as presented by the authors of the scientific work):

"Hass avocados, the most common commercial avocado cultivars in the world, contain a variety of essential nutrients and important phytochemicals. Although the official avocado serving is one-fifth of a fruit (30 g), according to NHANES analysis the average consumption is one-half an avocado (68 g), which provides a nutrient and phytochemical dense food consisting of the following: dietary fiber (4.6 g), total sugar (0.2 g), potassium (345 mg), sodium (5.5 mg), magnesium (19.5 mg), vitamin A (43 μg), vitamin C (6.0 mg), vitamin E (1.3 mg), vitamin K1 (14 μg), folate (60 mg), vitamin B-6 (0.2 mg), niacin (1.3 mg), pantothenic acid (1.0 mg), riboflavin (0.1 mg), choline (10 mg), lutein/zeaxanthin (185 μg), phytosterols (57 mg), and high-monounsaturated fatty acids (6.7 g) and 114 kcals or 1.7 kcal/g. The avocado oil consists of 71% monounsaturated fatty acids (MUFA), 13% polyunsaturated fatty acids (PUFA), and 16% saturated fatty acids (SFA), which helps to promote healthy blood lipid profiles and enhance the bioavailability of fat soluble vitamins and phytochemicals from the avocado or other fruits and vegetables, naturally low in fat, which are consumed with avocados. There are eight preliminary clinical studies showing that avocado consumption helps support cardiovascular health. Exploratory studies suggest that avocados may support weight management and healthy aging."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Conclusions (as presented by the authors of the scientific work):

"In the context of a healthy diet, consumption of avocados can fit into a full range of healthy eating plans (e.g., DASH diet plan). According to NHANES data, the average avocado consumption is one-half fruit, which provides for a nutrient and phytochemical dense food consisting of significant levels of the following: dietary fiber, potassium, magnesium, vitamin A, vitamin C, vitamin E, vitamin K1, folate, vitamin B-6, niacin, pantothenic acid, riboflavin, choline, lutein/zeaxanthin, phytosterols, and MUFA rich oil at 1.7 kcal/g. This caloric density is medium-low because an avocado is about 80% by weight is water (72%) and dietary fiber (6.8%). Unlike the typical fruit, avocados contain a very low sugar content with only about 0.2 g sugar per one-half fruit. There are eight preliminary avocado cardiovascular health clinical studies that have consistently demonstrated positive heart healthy effects on blood lipids profiles. This is primarily because of avocado's low SFA and high-unsaturated fatty acids (MUFA and PUFA) content, but its natural phytosterols and dietary fiber may play potential secondary cholesterol lowering roles. Avocados also have a diverse range of other nutrients and phytochemicals that may have beyond cholesterol vascular health benefits. In particular, avocado's potassium and lutein may help promote normal blood pressure and help to control oxidative/inflammatory stress, respectfully. The consumption of avocados with salads or salsa increases the bioavailability of carotenoids multi-fold, which may add to the potential health benefits. More comprehensive avocado clinical research is underway to significantly expand the scientific understanding of avocados in cardiovascular health, weight management, blood glucose control and healthy living."


Full-text access of the referenced scientific work:

Dreher ML, Davenport AJ. Hass avocado composition and potential health
effects. Crit Rev Food Sci Nutr. 2013;53(7):738-50. doi:
10.1080/10408398.2011.556759. Review. PubMed PMID: 23638933; PubMed Central
PMCID: PMC3664913.
https://www.researchgate.net/publication/236613037_Hass_Avocado_Composition_and_Potential_Health_Effects


Webmaster:

Prof. Atanas G. Atanasov (Dr. habil., PhD)
https://about.me/Atanas_At


Sunday, April 2, 2017

Recent advances in Parkinson's disease therapy


Abstract (as presented by the author of the scientific work):

"This article summarizes (1) the recent achievements to further improve symptomatic therapy of motor Parkinson's disease (PD) symptoms, (2) the still-few attempts to systematically search for symptomatic therapy of non-motor symptoms in PD, and (3) the advances in the development and clinical testing of compounds which promise to offer disease modification in already-manifest PD. However, prevention (that is, slowing or stopping PD in a prodromal stage) is still a dream and one reason for this is that we have no consensus on primary endpoints for clinical trials which reflect the progression in prodromal stages of PD, such as in rapid eye movement sleep behavior disorder (RBD) -a methodological challenge to be met in the future."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Conclusions (as presented by the author of the scientific work):

"Neurologists have to accept that the majority of patients with PD, even at the very early stage of neurological diagnosis, actually present a late-stage phenotype of an alpha-synucleinopathy. Thus, PD has started at least 20 years before it manifests in the clinic with its motor symptoms. Neurologists will likely have to shift their clinical and diagnostic focus away from the dopaminergic system to symptoms related to different parts of the nervous system, such as the enteric system62, the brainstem with its autonomic control areas, the locus coeruleus57, or even the skin. If the dream of a disease-modifying therapy is to come true, neuroscience, drug development, and physician scientists face at least two challenges. First, drug development will target the aggregation and propagation of alpha-synuclein and of related mechanisms as well as mitochondrial dysfunction; second, a major effort has to be made to enhance the diagnostic methodology in order to identify a primary endpoint for clinical neuroprotective trials, not only in early motor PD but also in the prodromal stages of PD82–84. It has never been so exciting as today to work in the field of PD, and we should share this belief with the patients we diagnose, treat, and care for."


Full-text access of the referenced scientific work:

Oertel WH. Recent advances in treating Parkinson's disease. F1000Res. 2017 Mar
13;6:260. doi: 10.12688/f1000research.10100.1. eCollection 2017. Review. PubMed
PMID: 28357055; PubMed Central PMCID: PMC5357034.
https://f1000research.com/articles/6-260/v1


Webmaster:

Prof. Atanas G. Atanasov (Dr. habil., PhD)
https://about.me/Atanas_At