Gut microbiome-oriented therapy for metabolic diseases: challenges and opportunities towards clinical translation

2021 ◽  
Author(s):  
Xueli Zhang ◽  
Xiaoying Cai ◽  
Xiao Zheng
Keyword(s):  
Gut Microbiome ◽  
Metabolic Diseases ◽  
Clinical Translation ◽  
Challenges And Opportunities

Folate and vitamin B-12 deficiencies additively impaired memory function and disturbed the gut microbiota in amyloid-β infused rats

2019 ◽  
pp. 1-13 ◽  
Author(s):  
Sunmin Park ◽  
Sunna Kang ◽  
Da Sol Kim
Keyword(s):  
Insulin Resistance ◽  
Gut Microbiota ◽  
Insulin Signaling ◽  
Gut Microbiome ◽  
Metabolic Diseases ◽  
Memory Function ◽  
Amyloid Β ◽  
Impaired Memory ◽  
Ca1 Region ◽  
Folate And Vitamin B12

Abstract. Folate and vitamin B12(V-B12) deficiencies are associated with metabolic diseases that may impair memory function. We hypothesized that folate and V-B12 may differently alter mild cognitive impairment, glucose metabolism, and inflammation by modulating the gut microbiome in rats with Alzheimer’s disease (AD)-like dementia. The hypothesis was examined in hippocampal amyloid-β infused rats, and its mechanism was explored. Rats that received an amyloid-β(25–35) infusion into the CA1 region of the hippocampus were fed either control(2.5 mg folate plus 25 μg V-B12/kg diet; AD-CON, n = 10), no folate(0 folate plus 25 μg V-B12/kg diet; AD-FA, n = 10), no V-B12(2.5 mg folate plus 0 μg V-B12/kg diet; AD-V-B12, n = 10), or no folate plus no V-B12(0 mg folate plus 0 μg V-B12/kg diet; AD-FAB12, n = 10) in high-fat diets for 8 weeks. AD-FA and AD-VB12 exacerbated bone mineral loss in the lumbar spine and femur whereas AD-FA lowered lean body mass in the hip compared to AD-CON(P < 0.05). Only AD-FAB12 exacerbated memory impairment by 1.3 and 1.4 folds, respectively, as measured by passive avoidance and water maze tests, compared to AD-CON(P < 0.01). Hippocampal insulin signaling and neuroinflammation were attenuated in AD-CON compared to Non-AD-CON. AD-FAB12 impaired the signaling (pAkt→pGSK-3β) and serum TNF-α and IL-1β levels the most among all groups. AD-CON decreased glucose tolerance by increasing insulin resistance compared to Non-AD-CON. AD-VB12 and AD-FAB12 increased insulin resistance by 1.2 and 1.3 folds, respectively, compared to the AD-CON. AD-CON and Non-AD-CON had a separate communities of gut microbiota. The relative counts of Bacteroidia were lower and those of Clostridia were higher in AD-CON than Non-AD-CON. AD-FA, but not V-B12, separated the gut microbiome community compared to AD-CON and AD-VB12(P = 0.009). In conclusion, folate and B-12 deficiencies impaired memory function by impairing hippocampal insulin signaling and gut microbiota in AD rats.

Polymeric micelles as drug delivery systems in cancer: challenges and opportunities

Nanomedicine ◽  
2021 ◽  
Author(s):  
Swati Biswas
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Polymeric Micelles ◽  
Delivery Systems ◽  
Clinical Translation ◽  
Current Status ◽  
Chemotherapeutic Drugs ◽  
Challenges And Opportunities

Tweetable abstract Micelles are nanocarriers for hydrophobic chemotherapeutic drugs. This editorial discusses the current status of preclinical micellar research and sheds light on the possibility of their clinical translation.

scholarly journals Gut microbiome activity contributes to individual variation in glycemic response in adults

2019 ◽  
Author(s):  
Hal Tily ◽  
Ally Perlina ◽  
Eric Patridge ◽  
Stephanie Gline ◽  
Matvey Genkin ◽  
...  
Keyword(s):  
Individual Variation ◽  
Gut Microbiome ◽  
Metabolic Diseases ◽  
Nutritional Composition ◽  
Gradient Boosting ◽  
Glycemic Response ◽  
Activity Data ◽  
Gradient Boosting Machine ◽  
Functional Features ◽  
First Time

AbstractLimiting post-meal glycemic response is an important factor in reducing the risk of chronic metabolic diseases, and contributes to significant health benefits in people with elevated levels of blood sugar. In this study, we collected gut microbiome activity (i.e., metatranscriptomic) data and measured the glycemic responses of 550 adults who consumed more than 30,000 meals from omnivore or vegetarian/gluten-free diets. We demonstrate that gut microbiome activity makes a statistically significant contribution to individual variation in glycemic response, in addition to anthropometric factors and the nutritional composition of foods. We describe predictive models (multilevel mixed-effects regression and gradient boosting machine) of variation in glycemic response among individuals ingesting the same foods. We introduce functional features aggregated from microbial activity data as candidates for association with mechanisms of glycemic control. In summary, we demonstrate for the first time that metatranscriptomic activity of the gut microbiome is correlated with glycemic response among adults.

Designing Poly-agonists for Treatment of Metabolic Diseases: Challenges and Opportunities

Drugs ◽  
2019 ◽  
Vol 79 (11) ◽  
pp. 1187-1197 ◽  
Author(s):  
Jonas Petersen ◽  
Kristian Strømgaard ◽  
Bente Frølund ◽  
Christoffer Clemmensen
Keyword(s):  
Metabolic Diseases ◽  
Challenges And Opportunities

scholarly journals Gut Microbiome, Intestinal Permeability, and Tissue Bacteria in Metabolic Disease: Perpetrators or Bystanders?

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1082 ◽  
Author(s):  
Rima M. Chakaroun ◽  
Lucas Massier ◽  
Peter Kovacs
Keyword(s):  
Metabolic Disease ◽  
Intestinal Permeability ◽  
Systemic Inflammation ◽  
Gut Microbiome ◽  
Metabolic Diseases ◽  
Treatment Strategies ◽  
Intestinal Barrier ◽  
Intestinal Bacteria ◽  
Current Evidence ◽  
Microbial Culture

The emerging evidence on the interconnectedness between the gut microbiome and host metabolism has led to a paradigm shift in the study of metabolic diseases such as obesity and type 2 diabetes with implications on both underlying pathophysiology and potential treatment. Mounting preclinical and clinical evidence of gut microbiota shifts, increased intestinal permeability in metabolic disease, and the critical positioning of the intestinal barrier at the interface between environment and internal milieu have led to the rekindling of the “leaky gut” concept. Although increased circulation of surrogate markers and directly measurable intestinal permeability have been linked to increased systemic inflammation in metabolic disease, mechanistic models behind this phenomenon are underdeveloped. Given repeated observations of microorganisms in several tissues with congruent phylogenetic findings, we review current evidence on these unanticipated niches, focusing specifically on the interaction between gut permeability and intestinal as well as extra-intestinal bacteria and their joint contributions to systemic inflammation and metabolism. We further address limitations of current studies and suggest strategies drawing on standard techniques for permeability measurement, recent advancements in microbial culture independent techniques and computational methodologies to robustly develop these concepts, which may be of considerable value for the development of prevention and treatment strategies.

Gut microbiome and metabolic diseases

2013 ◽  
Vol 36 (1) ◽  
pp. 103-114 ◽  
Author(s):  
Shinji Fukuda ◽  
Hiroshi Ohno
Keyword(s):  
Gut Microbiome ◽  
Metabolic Diseases

scholarly journals Longitudinal analysis of serum cytokine levels and gut microbial abundance links IL-17/IL-22 with Clostridia and insulin sensitivity in humans

2020 ◽  
Author(s):  
Ada Admin ◽  
Xin Zhou ◽  
Jethro S. Johnson ◽  
Daniel Spakowicz ◽  
Wenyu Zhou ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Gut Microbiome ◽  
Metabolic Diseases ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Serum Levels ◽  
Discrete Groups ◽  
Cytokine Levels ◽  
Using Data ◽  
Study Participants

Recent studies using mouse models suggest that interaction between the gut microbiome and IL-17/IL-22 producing cells plays a role in the development of metabolic diseases. We investigated this relationship in humans using data from the prediabetes study of the Integrated Human Microbiome Project (iHMP). Specifically, we addressed the hypothesis that early in the onset of metabolic diseases there is a decline in serum levels of IL-17/IL-22, with concomitant changes in the gut microbiome. Clustering iHMP study participants on the basis of longitudinal IL-17/IL-22 profiles identified discrete groups. Individuals distinguished by low levels of IL-17/IL-22 were linked to established markers of metabolic disease, including insulin sensitivity. These individuals also displayed gut microbiome dysbiosis, characterized by decreased diversity, and IL-17/IL-22-related declines in the phylum <i>Firmicutes,</i> class <i>Clostridia</i>, and<i> </i>order <i>Clostridiales.</i> This ancillary analysis of the iHMP data therefore supports a link between the gut microbiome, IL-17/IL-22 and the onset of metabolic diseases. This raises the possibility for novel, microbiome-related therapeutic targets that may effectively alleviate metabolic diseases in humans as they do in animal models.

scholarly journals Metabiotics: prospects, challenges and opportunities

2019 ◽  
Vol 2 (13) ◽  
pp. 43-48
Author(s):  
B. A. Shenderov ◽  
E. I. Tkachenko ◽  
M. M. Zakharchenko ◽  
A. V. Sinitsa
Keyword(s):  
Personalized Medicine ◽  
Chemical Structure ◽  
Metabolic Diseases ◽  
Fermented Foods ◽  
Structural Components ◽  
Physiological Regulator ◽  
Challenges And Opportunities ◽  
Symbiotic Microbiota ◽  
Modern Condition ◽  
Living Bacteria

In this review authors discuss modern condition of treatment and prophylaxis of human metabolic diseases associated with microecological imbalance of intestinal symbiotic microbiota. Now the most frequently for these aims various probiotic nutrient additives and functional fermented foods prepared on the basis of living bacteria have been used. Unfortunately such probiotics have not possessed the real effectiveness and are not completely safe. Instead of traditional commercially available living probiotics the authors suggest to use novel microecological means (metabiotics) that are structural components of probiotic bactrerial strains, and/or their metabolites and/or signaling molecules with known chemical structure. Metabiotics can optimize host‑specific physiological, regulator, metabolic and/or hormone/behavior functions and reactions. Metabiotics possess some advantages in future personalized medicine because they have exact chemical structure, well dosed, safe and long shelf‑life.

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