scholarly journals Insights into the Role of the Microbiota and of Short-Chain Fatty Acids in Rubinstein–Taybi Syndrome

2021 ◽  
Vol 22 (7) ◽  
pp. 3621
Author(s):  
Elisabetta Di Fede ◽  
Emerenziana Ottaviano ◽  
Paolo Grazioli ◽  
Camilla Ceccarani ◽  
Antonio Galeone ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Neurodevelopmental Disorder ◽  
Short Chain Fatty Acids ◽  
Therapeutic Interventions ◽  
Short Chain ◽  
Patient Specific ◽  
Microbiota Composition ◽  
In Vivo Models

The short-chain fatty acid butyrate, produced by the gut microbiota, acts as a potent histone deacetylase (HDAC) inhibitor. We assessed possible ameliorative effects of butyrate, relative to other HDAC inhibitors, in in vitro and in vivo models of Rubinstein–Taybi syndrome (RSTS), a severe neurodevelopmental disorder caused by variants in the genes encoding the histone acetyltransferases CBP and p300. In RSTS cell lines, butyrate led to the patient-specific rescue of acetylation defects at subtoxic concentrations. Remarkably, we observed that the commensal gut microbiota composition in a cohort of RSTS patients is significantly depleted in butyrate-producing bacteria compared to healthy siblings. We demonstrate that the effects of butyrate and the differences in microbiota composition are conserved in a Drosophila melanogaster mutant for CBP, enabling future dissection of the gut–host interactions in an in vivo RSTS model. This study sheds light on microbiota composition in a chromatinopathy, paving the way for novel therapeutic interventions.

scholarly journals Potential Modulatory Microbiome Therapies for Prevention or Treatment of Inflammatory Bowel Diseases

2021 ◽  
Vol 14 (6) ◽  
pp. 506
Author(s):  
Daan V. Bunt ◽  
Adriaan J. Minnaard ◽  
Sahar El Aidy
Keyword(s):  
Inflammatory Bowel Disease ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
In Vivo Models ◽  
Gut Homeostasis ◽  
Bowel Diseases ◽  
Inflammatory Bowel

A disturbed interaction between the gut microbiota and the mucosal immune system plays a pivotal role in the development of inflammatory bowel disease (IBD). Various compounds that are produced by the gut microbiota, from its metabolism of diverse dietary sources, have been found to possess anti-inflammatory and anti-oxidative properties in in vitro and in vivo models relevant to IBD. These gut microbiota-derived metabolites may have similar, or more potent gut homeostasis-promoting effects compared to the widely-studied short-chain fatty acids (SCFAs). Available data suggest that mainly members of the Firmicutes are responsible for producing metabolites with the aforementioned effects, a phylum that is generally underrepresented in the microbiota of IBD patients. Further efforts aiming at characterizing such metabolites and examining their properties may help to develop novel modulatory microbiome therapies to treat or prevent IBD.

Short-Chain Fatty Acids Prevent Diabetic Nephropathy In Vivo and In Vitro

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 92-OR ◽  
Author(s):  
WEI HUANG ◽  
YONG XU ◽  
YOUHUA XU ◽  
LUPING ZHOU ◽  
CHENLIN GAO
Keyword(s):  
Fatty Acids ◽  
Diabetic Nephropathy ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Chain Fatty Acids

scholarly journals The relationship between gut microbiota, short-chain fatty acids and type 2 diabetes mellitus: the possible role of dietary fibre

2021 ◽  
Author(s):  
Dominic Salamone ◽  
Angela Albarosa Rivellese ◽  
Claudia Vetrani
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Dietary Fibre ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Microbiota Composition ◽  
The Relationship ◽  
Chain Fatty Acids

AbstractGut microbiota and its metabolites have been shown to influence multiple physiological mechanisms related to human health. Among microbial metabolites, short-chain fatty acids (SCFA) are modulators of different metabolic pathways. On the other hand, several studies suggested that diet might influence gut microbiota composition and activity thus modulating the risk of metabolic disease, i.e. obesity, insulin resistance and type 2 diabetes. Among dietary component, dietary fibre may play a pivotal role by virtue of its prebiotic effect on fibre-fermenting bacteria, that may increase SCFA production. The aim of this review was to summarize and discuss current knowledge on the impact of dietary fibre as modulator of the relationship between glucose metabolism and microbiota composition in humans. More specifically, we analysed evidence from observational studies and randomized nutritional intervention investigating the relationship between gut microbiota, short-chain fatty acids and glucose metabolism. The possible mechanisms behind this association were also discussed.

scholarly journals Biophysical studies of protein misfolding and aggregation in in vivo models of Alzheimer's and Parkinson's diseases

2020 ◽  
Vol 53 ◽  
Author(s):  
Tessa Sinnige ◽  
Karen Stroobants ◽  
Christopher M. Dobson ◽  
Michele Vendruscolo
Keyword(s):  
Protein Misfolding ◽  
Molecular Mechanisms ◽  
Amyloid Β ◽  
Therapeutic Interventions ◽  
In Vivo Models ◽  
Disease Modifying Drugs ◽  
Parkinson’S Diseases ◽  
Protein Misfolding And Aggregation

Abstract Neurodegenerative disorders, including Alzheimer's (AD) and Parkinson's diseases (PD), are characterised by the formation of aberrant assemblies of misfolded proteins. The discovery of disease-modifying drugs for these disorders is challenging, in part because we still have a limited understanding of their molecular origins. In this review, we discuss how biophysical approaches can help explain the formation of the aberrant conformational states of proteins whose neurotoxic effects underlie these diseases. We discuss in particular models based on the transgenic expression of amyloid-β (Aβ) and tau in AD, and α-synuclein in PD. Because biophysical methods have enabled an accurate quantification and a detailed understanding of the molecular mechanisms underlying protein misfolding and aggregation in vitro, we expect that the further development of these methods to probe directly the corresponding mechanisms in vivo will open effective routes for diagnostic and therapeutic interventions.

scholarly journals Effects of Rich in Β-Glucans Edible Mushrooms on Aging Gut Microbiota Characteristics: An In Vitro Study

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2806 ◽  
Author(s):  
Evdokia K. Mitsou ◽  
Georgia Saxami ◽  
Emmanuela Stamoulou ◽  
Evangelia Kerezoudi ◽  
Eirini Terzi ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Wheat Straw ◽  
In Vitro Study ◽  
Short Chain Fatty Acids ◽  
Edible Mushrooms ◽  
Elderly Subjects ◽  
Microbiota Composition ◽  
The Impact ◽  
Gut Microbiota Composition

Alterations of gut microbiota are evident during the aging process. Prebiotics may restore the gut microbial balance, with β-glucans emerging as prebiotic candidates. This study aimed to investigate the impact of edible mushrooms rich in β-glucans on the gut microbiota composition and metabolites by using in vitro static batch culture fermentations and fecal inocula from elderly donors (n = 8). Pleurotus ostreatus, P. eryngii, Hericium erinaceus and Cyclocybe cylindracea mushrooms derived from various substrates were examined. Gut microbiota composition (quantitative PCR (qPCR)) and short-chain fatty acids (SCFAs; gas chromatography (GC)) were determined during the 24-h fermentation. P. eryngii induced a strong lactogenic effect, while P. ostreatus and C. cylindracea induced a significant bifidogenic effect (p for all <0.05). Furthermore, P. eryngii produced on wheat straw and the prebiotic inulin had comparable Prebiotic Indexes, while P. eryngii produced on wheat straw/grape marc significantly increased the levels of tested butyrate producers. P. ostreatus, P. eryngii and C. cylindracea had similar trends in SCFA profile; H. erinaceus mushrooms were more diverse, especially in the production of propionate, butyrate and branched SCFAs. In conclusion, mushrooms rich in β-glucans may exert beneficial in vitro effects in gut microbiota and/or SCFAs production in elderly subjects.

scholarly journals Exogenous and endogenous HDAC inhibitor effects in Rubinstein-Taybi syndrome models

2020 ◽  
Author(s):  
Elisabetta Di Fede ◽  
Emerenziana Ottaviano ◽  
Paolo Grazioli ◽  
Camilla Ceccarani ◽  
Chiara Parodi ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Hdac Inhibitors ◽  
Clinical Signs ◽  
Microbiota Composition ◽  
Autosomal Dominant Disorder ◽  
Donor Cells ◽  
Neurodevelopmental Impairment ◽  
Gut Microbiota Composition

ABSTRACTRubinstein-Taybi syndrome (RSTS) is an autosomal dominant disorder with specific clinical signs and neurodevelopmental impairment. The two known proteins altered in the majority of RSTS patients are the histone acetylation regulators CBP and p300. For assessing possible ameliorative effects of exogenous and endogenous HDAC inhibitors (HDACi), we exploited in vivo and in vitro RSTS models. First, HDACi effects were tested on Drosophila melanogaster, showing molecular rescue. In the same model, we observed a shift in gut microbiota composition. We then studied HDACi effects in RSTS cell lines compared to healthy donor cells. We observed patients-specific molecular rescue of acetylation defects at subtoxic concentrations. Finally, we assessed commensal gut microbiota composition in a cohort of RSTS patients compared to healthy siblings. Intriguingly, we observed a significant depletion in butyrate-producing bacteria in RSTS patients. In conclusion, this study reports the possibility of modulating acetylation equilibrium by HDACi treatments and the importance of microbiota composition in a chromatinopathy.

scholarly journals Prebiotics, Probiotics and Synbiotic for Bone Health

2021 ◽  
Author(s):  
Bolaji Lilian Ilesanmi-Oyelere ◽  
Marlena Cathorina Kruger
Keyword(s):  
Fatty Acids ◽  
Bone Resorption ◽  
Bone Health ◽  
Calcium Absorption ◽  
Osteoclast Differentiation ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Micro Organisms

Prebiotics, probiotics and synbiotics has been shown to enhance calcium absorption, gut and bone health. Probiotics are also known to ferment prebiotics to produce the fermentative substrates such as short chain fatty acids (SCFAs), mainly acetate, butyrate and propionate with the help of beneficial micro-organisms in the gut. The expression of these SCFAs has been associated with the inhibition of osteoclast differentiation and bone resorption both in vitro and in vivo. In this review, we discuss the benefits of SCFAs and ways in which prebiotics and probiotics affect bone health by the reduction of inflammation in the gut and the bone.

scholarly journals Anti-Inflammatory Activities of Pentaherbs formula and Its Influence on Gut Microbiota in Allergic Asthma

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2776 ◽  
Author(s):  
Miranda Tsang ◽  
Sau-Wan Cheng ◽  
Jing Zhu ◽  
Karam Atli ◽  
Ben Chan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Allergic Asthma ◽  
Herbal Medicines ◽  
Oral Intake ◽  
Allergic Diseases ◽  
Short Chain Fatty Acids ◽  
Mice Model ◽  
Anti Inflammatory

Allergic asthma is a highly prevalent airway inflammatory disease, which involves the interaction between the immune system, environmental and genetic factors. Co-relation between allergic asthma and gut microbiota upon the change of diet have been widely reported, implicating that oral intake of alternative medicines possess a potential in the management of allergic asthma. Previous clinical, in vivo, and in vitro studies have shown that the Pentaherbs formula (PHF) comprising five traditional Chinese herbal medicines Lonicerae Flos, Menthae Herba, Phellodendri Cortex, Moutan Cortex, and Atractylodis Rhizoma possesses an anti-allergic and anti-inflammatory potential through suppressing various immune effector cells. In the present study, to further investigate the anti-inflammatory activities of PHF in allergic asthma, intragastrical administration of PHF was found to reduce airway hyperresponsiveness, airway wall remodeling and goblet cells hyperplasia in an ovalbumin (OVA)-induced allergic asthma mice model. PHF also significantly suppressed pulmonary eosinophilia and asthma-related cytokines IL-4 and IL-33 in bronchoalveolar lavage (BAL) fluid. In addition, PHF modulated the splenic regulatory T cells population, up-regulated regulatory interleukin (IL)-10 in serum, altered the microbial community structure and the short chain fatty acids content in the gut of the asthmatic mice. This study sheds light on the anti-inflammatory activities of PHF on allergic asthma. It also provides novel in vivo evidence that herbal medicines can ameliorate symptoms of allergic diseases may potentially prevent the development of subsequent atopic disorder such as allergic asthma through the influence of the gut microbiota.

scholarly journals Honeybee gut microbiota promotes host weight gain via bacterial metabolism and hormonal signaling

2017 ◽  
Vol 114 (18) ◽  
pp. 4775-4780 ◽  
Author(s):  
Hao Zheng ◽  
J. Elijah Powell ◽  
Margaret I. Steele ◽  
Carsten Dietrich ◽  
Nancy A. Moran
Keyword(s):  
Weight Gain ◽  
Gut Microbiota ◽  
Microbial Metabolism ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Whole Body ◽  
Social Bees ◽  
Host Microbe Interactions ◽  
The Impact

Social bees harbor a simple and specialized microbiota that is spatially organized into different gut compartments. Recent results on the potential involvement of bee gut communities in pathogen protection and nutritional function have drawn attention to the impact of the microbiota on bee health. However, the contributions of gut microbiota to host physiology have yet to be investigated. Here we show that the gut microbiota promotes weight gain of both whole body and the gut in individual honey bees. This effect is likely mediated by changes in host vitellogenin, insulin signaling, and gustatory response. We found that microbial metabolism markedly reduces gut pH and redox potential through the production of short-chain fatty acids and that the bacteria adjacent to the gut wall form an oxygen gradient within the intestine. The short-chain fatty acid profile contributed by dominant gut species was confirmed in vitro. Furthermore, metabolomic analyses revealed that the gut community has striking impacts on the metabolic profiles of the gut compartments and the hemolymph, suggesting that gut bacteria degrade plant polymers from pollen and that the resulting metabolites contribute to host nutrition. Our results demonstrate how microbial metabolism affects bee growth, hormonal signaling, behavior, and gut physicochemical conditions. These findings indicate that the bee gut microbiota has basic roles similar to those found in some other animals and thus provides a model in studies of host–microbe interactions.

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