Gut Microbiome and Organ Fibrosis

Fibrosis is a pathological process associated with most chronic inflammatory diseases. It is defined by an excessive deposition of extracellular matrix proteins and can affect nearly every tissue and organ system in the body. Fibroproliferative diseases, such as intestinal fibrosis, liver cirrhosis, progressive kidney disease and cardiovascular disease, often lead to severe organ damage and are a leading cause of morbidity and mortality worldwide, for which there are currently no effective therapies available. In the past decade, a growing body of evidence has highlighted the gut microbiome as a major player in the regulation of the innate and adaptive immune system, with severe implications in the pathogenesis of multiple immune-mediated disorders. Gut microbiota dysbiosis has been associated with the development and progression of fibrotic processes in various organs and is predicted to be a potential therapeutic target for fibrosis management. In this review we summarize the state of the art concerning the crosstalk between intestinal microbiota and organ fibrosis, address the relevance of diet in different fibrotic diseases and discuss gut microbiome-targeted therapeutic approaches that are current being explored.     

Dietary Sodium and Potassium Intake: Data from the Mexican National Health and Nutrition Survey 2016

Population studies have demonstrated an association between sodium and potassium intake and blood pressure levels and lipids. The aim of this study was to describe the dietary intake and contribution of sodium and potassium to the Mexican diet, and to describe its association with nutrition status and clinical characteristics. We analyzed a national survey with 4219 participants. Dietary information was obtained with a 24-h recall. Foods and beverages were classified according to level of processing. The mean intake (mg/d) of Na was 1512 in preschool children, 2844 in school-age children, 3743 in adolescents, and 3132 in adults. The mean intake (mg/d) of K was 1616 in preschool children, 2256 in school-age children, 2967 in adolescents, and 3401 in adults. Processed and ultra-processed foods (UPF) contribute 49% of Na intake in preschool children, 50% in school-age children, 47% in adolescents, and 39% in adults. Adults with high Na intake had lower serum concentrations of cholesterol, HDL-c, and LDL-c. A significant proportion of the Mexican population has a high intake of Na (64–82%) and low K (58–73%). Strategies to reduce Na and increase K intake need to reduce the possibility of having high BP and serum lipid disturbances.     

Autonomic Nervous System Neuroanatomical Alterations Could Provoke and Maintain Gastrointestinal Dysbiosis in Autism Spectrum Disorder (ASD): A Novel Microbiome–Host Interaction Mechanistic Hypothesis

Dysbiosis secondary to environmental factors, including dietary patterns, antibiotics use, pollution exposure, and other lifestyle factors, has been associated to many non-infective chronic inflammatory diseases. Autism spectrum disorder (ASD) is related to maternal inflammation, although there is no conclusive evidence that affected individuals suffer from systemic low-grade inflammation as in many psychological and psychiatric diseases. However, neuro-inflammation and neuro–immune abnormalities are observed within ASD-affected individuals. Rebalancing human gut microbiota to treat disease has been widely investigated with inconclusive and contradictory findings. These observations strongly suggest that the forms of dysbiosis encountered in ASD-affected individuals could also originate from autonomic nervous system (ANS) functioning abnormalities, a common neuro–anatomical alteration underlying ASD. According to this hypothesis, overactivation of the sympathetic branch of the ANS, due to the fact of an ASD-specific parasympathetic activity deficit, induces deregulation of the gut–brain axis, attenuating intestinal immune and osmotic homeostasis. This sets-up a dysbiotic state, that gives rise to immune and osmotic dysregulation, maintaining dysbiosis in a vicious cycle. Here, we explore the mechanisms whereby ANS imbalances could lead to alterations in intestinal microbiome–host interactions that may contribute to the severity of ASD by maintaining the brain–gut axis pathways in a dysregulated state.     

P300 latency and amplitude in the diagnosis of dementia

P300 latency and amplitude were investigated in 10 normal elderly individuals, 10 institutionalized elderly persons with dementia not of the Alzheimer's types, and 10 elderly people with Alzheimer's disease. Significant differences between control and dementia groups (but not between dementia groups) were noted in the P300 latency, but not amplitude. Such differential latencies were observed in the anterior and in the left temporal and parietal areas of the brain.     

Dynamic porous organic polymers with tuneable crosslinking degree and porosity

Porous organic polymers (POPs) show enormous potential for applications in separation, organic electronics, and biomedicine due to the combination of high porosity, high stability, and ease of functionalisation. However, POPs are usually insoluble and amorphous materials making it very challenging to obtain structural information. Additionally, important parameters such as the exact molecular structure or the crosslinking degree are largely unknown, despite their importance for the final properties of the system. In this work, we introduced the reversible multi-fold nitroxide exchange reaction to the synthesis of POPs to tune and at the same time follow the crosslinking degree in porous polymer materials. We synthesised three different POPs based on the combination of linear, trigonal, and tetrahedral alkoxyamines with a tetrahedral nitroxide. We could show that modulating the equilibrium in the nitroxide exchange reaction, by adding or removing one nitroxide species, leads to changes in the crosslinking degree. Being able to modulate the crosslinking degree in POPs allowed us to investigate both the influence of the crosslinking degree and the structure of the molecular components on the porosity. The crosslinking degree of the frameworks was characterised using EPR spectroscopy and the porosity was determined using argon gas adsorption measurements. To guide the design of POPs for desired applications, our study reveals that multiple factors need to be considered such as the structure of the molecular building blocks, the synthetic conditions, and the crosslinking degree.

We synthesised three different POPs via a nitroxide exchange reaction and modulated their crosslinking degree. That allowed us to investigate the influence of the crosslinking degree and the structure of the molecular components on the porosity.

Various approaches to synthesise porous organic polymers (POPs)^1–3 and conjugated microporous polymers (CMPs)^4,5 have been developed to form extremely stable but at the same time highly porous solids based on simple organic building blocks.^6,7 The organic nature allows for functionalisation of the materials using organic chemistry, while the high porosity makes the active components accessible throughout the entire material.⁸ The combination of high porosity, high stability, and ease of functionalisation results in the enormous potential of POPs for applications in separation, organic electronics, and biomedicine.^2,9–14 However, unlike the related covalent organic frameworks (COFs),^15–20 metal–organic frameworks (MOFs)^21,22 or porous coordination polymers (PCPs),²³ the synthesis of POPs and CMPs is based on irreversible reactions, which leads to insoluble and amorphous materials and makes it very challenging to obtain structural information. Additionally, important parameters such as the exact molecular structure or the crosslinking degree are largely unknown, despite their unarguably large influence on the final properties of the system.^24,25To investigate the molecular structure of the organic linkers between the centres of two similar CMP materials, the group of Bunz and co-workers introduced molecular building blocks that were modified with digestible groups or cores, by substituting carbon with tin as the central atom.²⁴ This tin centre can be digested, resulting in molecular fragments of the frameworks, which were analysed using nuclear magnetic resonance (NMR) spectroscopy. The obtained fragments show a surprisingly varied chemical composition of these networks.²⁴ In a previous study, we could show that the introduction of digestible germanium nodes in one of the building blocks of POPs can also be used for partial disruption of the framework and therefore causing a decrease or allow tuning of the porosity.²⁵ In another approach, we introduced a poly(disulfide) hyper-crosslinked polymer, which can be surface modified using unreacted thiol functions on the surface of the material.²⁶ Digestion of the samples helped to quantify the functionalisation. Employing digestible crosslinker or nodes is an attractive approach to gain insight into the structure or functionalisation of the frameworks. However, it requires the destruction of the sample and does not allow to modulate or tune the crosslinking degree reversibly in one particular system.In order to tune and at the same time follow the crosslinking degree in porous polymer materials, we introduce the reversible multi-fold nitroxide exchange reaction to the synthesis of POPs. The nitroxide exchange reaction has been used in material science for self-assembly of polymer materials²⁷ or micron-sized crystals,²⁸ for surface functionalisation,²⁹ or introducing self-healing properties to materials.³⁰ In addition, the combination of light-sensitive alkoxyamines was employed in surface coating³¹ or the creation of systems out of their equilibrium.³² The radical nature of the involved nitroxide species allows to follow the progress of the reaction and to directly determine the crosslinking degree of the final material using fluorescence spectroscopy^33,34 and electron paramagnetic resonance (EPR) spectroscopy.^35,36 The dynamic nature of the nitroxide exchange reaction allowed us to tune the crosslinking degree of the materials by varying the ratio of the two nitroxide species involved in the reaction and thereby modulating the equilibrium conditions (see Fig. 1).Open in a separate windowFig. 1Dynamic equilibrium in the nitroxide exchange reaction using two different nitroxide species, TEMPO (red) and isoindoline (green). The free nitroxide radical species are electron paramagnetic resonance (EPR) active, while the bound species are EPR silent.Next to the crosslinking degree, also the structure, rigidity, and the intrinsic free volume of the molecular components of POPs or CMPs play an important role to obtain porosity in the final material.⁶ Cooper and co-workers showed the importance of monomer design for the pore size and surface area of CMPs by systematically varying the strut length in a series of molecular building blocks.³⁷In order to study the influence of both the molecular structure and the crosslinking degree on the porosity of the final material, we produced three different POPs based on the combination of linear, trigonal, and tetrahedral alkoxyamines with tetrahedral nitroxides. We characterised the frameworks using EPR spectroscopy and argon gas adsorption measurements to determine the crosslinking degree and porosity. Furthermore, we could show that modulating the equilibrium in the nitroxide exchange reaction, by adding or removing one nitroxide species, leads to changes in the crosslinking degree and investigated this influence on the porosity of the frameworks.     

Use of Private Sector Workforce Respiratory Disease Short-Term Disability Claims to Assess SARS-CoV-2, Mexico, 2020

We examined respiratory disease short-term disability claims submitted to the Mexican Social Security Institute during 2020. A total of 1,631,587 claims were submitted by 19.1 million insured workers. Cumulative incidence (8.5%) was 3.6 times higher than that for January 2015‒December-2019. Workers in healthcare, social assistance, self-service, and retail stores were disproportionately affected.     

Ramadan Nutritional Strategy: Professional Soccer Player Case Study

The period of Ramadan induces changes in the usual eating patterns of individuals. During this period, Muslims must abstain from drinking and eating from dawn to dusk. Therefore, some research conducted on professional soccer players has observed that during and/or after Ramadan, performance, running speed, agility, dribbling speed, and endurance and/or skill performance in athletic events may be negatively affected by Ramadan intermittent fasting (RIF). The objective of this study was to analyze the influence of a dietary plan during RIF on performance and body composition in a professional soccer player. A 20-year-old elite player (86.0 kg, 188.5 cm) followed a dietary-nutritional plan with an isocaloric diet and was supplemented with glycerol. The athlete’s strength and power in the lower limbs was assessed by performing a countermovement jump (CMJ) and Abalakov vertical jump (ABK) before and after Ramadan. After nutritional planning, the patient’s body composition improved in terms of fat loss (6.61 to 5.70%) and muscle mass gain (50.26 to 51.50%). In addition, this translated into improvements in performance tests, both in the CMJ (36.72 to 40.00 cm) and ABK (39.16 to 49.34 cm). In conclusion, during a period of fasting, personalised nutritional planning and an appropriate supplementation and rest protocol can improve the body composition and performance of soccer players.     

Colonic Microbiota Profile Characterization of the Responsiveness to Dietary Fibre Treatment in Hypercholesterolemia

This study aimed to determine how the microbiota profile might be predisposed to a better response in blood lipid profiles due to dietary fibre supplementation. A three-arm intervention study that included three different fibre types (mainly insoluble, soluble, and antioxidant fibre) supplemented (19.2 g/day) during 2 months in individuals with hypercholesterolemia was developed. Changes in faecal microbiota and blood lipid profile after fibre supplementation were determined. In all volunteers, regardless of fibre type, an increase in the abundance of Bifidobacterium was observed, and similarly, an inverse relationship between faecal propionic acid and blood LDL-cholesterol, LDL particle size, and LDL/HDL particle ratio (p-values 0.0067, 0.0002, and 0.0067, respectively) was observed. However, not all volunteers presented an improvement in lipid profile. The non-responders to fibre treatment showed a decrease in microbiota diversity (Shannon and Simpson diversity index p-values of 0.0110 and 0.0255, respectively) after the intervention; where the reduction in short-chain fatty acids (SCFAs) producing bacterial genera such as Clostridium XIVa and Ruminococcus after dietary fibre treatment was the main difference. It was concluded that the non-responsiveness to dietary fibre treatment might be mediated by the lack of ability to maintain a stable SCFA producing bacteria diversity and composition after extra fibre intake.     

Role of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in Peyronie's disease:a new diagnostic approach to predict the stage of the disease?

Neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)have been associated with multiple entities and several types of cancers.They can be ass...