Association between seizure reduction during ketogenic diet treatment of epilepsy and changes in circulatory metabolites and gut microbiota composition.

Background: The ketogenic diet (KD) is a high fat, sufficient protein, and low carbohydrate dietary therapy for drug-resistant epilepsy. The underlying mechanisms of action of the KD remain unclear. In mice, the microbiota is necessary for the anti-seizure effect and specific microbes influence circulatory levels of metabolites that are linked to seizure reduction.

Investigations of microbiota composition and neuroactive pathways in association with symptoms of stress and depression in a cohort of healthy women.

Background: Despite mounting evidence of gut-brain involvement in psychiatric conditions, functional data remain limited, and analyses of other microbial niches, such as the vaginal microbiota, are lacking in relation to mental health. This aim of this study was to investigate if the connections between the gut microbiome and mental health observed in populations with a clinical diagnosis of mental illness extend to healthy women experiencing stress and depressive symptoms. Additionally, this study examined the functional pathways of the gut microbiota according to the levels of psychological symptoms.

Plasma bile acids in association with Crohn's disease.

Background: In addition to facilitating lipid digestions, bile acids (BA) are signalling molecules acting on receptors on immune cells and along the gastrointestinal (GI) tract. The aim of this study was to assess if altered bile acid profiles in plasma are associated with Crohn's disease (CD).

Method: This cross-sectional study included individuals (aged ≥18 years) referred for colonoscopy at a tertiary centre in Stockholm between 2016 and 2019.

Fecal transfers from children on the ketogenic diet mimic the anti-seizure effect in mice.

The ketogenic diet (KD) mediates its anti-seizure effect through the gut microbiota in epilepsy mouse models. Lum et al. demonstrated that fecal microbiota from children with epilepsy treated with the KD decreases seizure susceptibility in mice after transfer.

Evaluation of plasma Short chain fatty acid levels as markers for Inflammatory bowel disease.

Background: Specific variations of short chain fatty acids in fecal samples have been shown for patients with inflammatory bowel disease. The aim of this study was to assess if Crohn's disease and ulcerative colitis are associated with altered concentrations of short chain fatty acids also in blood plasma.

Method: Between 2016-2019, Swedish adults referred to a tertiary center for colonoscopy were asked to participate in a cross-sectional study.

Mucosal and Plasma Metabolomes in New-onset Paediatric Inflammatory Bowel Disease: Correlations with Disease Characteristics and Plasma Inflammation Protein Markers.

Background And Aims: To advance the understanding of inflammatory bowel disease [IBD] pathophysiology, we compared the mucosal and plasma metabolomes between new-onset paediatric IBD patients and symptomatic non-IBD controls, and correlated plasma inflammation markers and disease characteristics with the altered metabolites.

Methods: Paired colonic and ileal biopsies and plasma from 67 treatment-naïve children with incident Crohn's disease [CD; n = 47], ulcerative colitis [UC; n = 9], and non-IBD controls [n = 11] were analysed using ultra-performance liquid chromatography-mass spectrometry [UPLC-MS/MS]. Inflammatory plasma proteins [n = 92] were assessed.

Higher levels of Bifidobacteria and tumor necrosis factor in children with drug-resistant epilepsy are associated with anti-seizure response to the ketogenic diet.

Background: Recently, studies have suggested a role for the gut microbiota in epilepsy. Gut microbial changes during ketogenic diet (KD) treatment of drug-resistant epilepsy have been described. Inflammation is associated with certain types of epilepsy and specific inflammation markers decrease during KD.

Alterations of gut microbiota in patients with active pulmonary tuberculosis in China: a pilot study.

Background: The aim of this study was to identify the differences in diversity, composition, and function of the gut microbiota between tuberculosis (TB) patients and healthy controls (HCs).

Methods: A cross-sectional study was conducted in three cities of China. Stool samples from 94 treatment-naive TB patients and 62 HCs were analyzed by 16S rRNA gene sequencing.

Bioinformatics and machine learning in gastrointestinal microbiome research and clinical application.

The scientific community currently defines the human microbiome as all the bacteria, viruses, fungi, archaea, and eukaryotes that occupy the human body. When considering the variable locations, composition, diversity, and abundance of our microbial symbionts, the sheer volume of microorganisms reaches hundreds of trillions. With the onset of next generation sequencing (NGS), also known as high-throughput sequencing (HTS) technologies, the barriers to studying the human microbiome lowered significantly, making in-depth microbiome research accessible.

Longitudinal profiling of gut microbiome among tuberculosis patients under anti-tuberculosis treatment in China: protocol of a prospective cohort study.

Background: Anti-tuberculosis therapy requires at least six-month treatment with continuous administration of combined antibiotics, including isoniazid, rifampicin, pyrazinamide, and ethambutol. The long-term exposure to antibiotics could cause consequent changes in gut microbiota, which may alter the gastrointestinal function and drug absorption in patients, thereby affect the outcome of treatment. The study aims to characterize the longitudinal changes of gut microbiota among tuberculosis (TB) patients under standardized first-line treatment and provide an understanding of the association between alterations in gut microbiota composition and unfavorable clinical outcomes.

Microbe-host interplay in atopic dermatitis and psoriasis.

Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers.

The gut microbiome and epilepsy.

Recently, evidence from both animal studies and human cases has emerged that a dysbiosis in the gut may be associated with certain forms of epilepsy. The ketogenic diet is an alternative treatment of drug-resistant epilepsy, although its precise mechanism of action has been unclear. It has now been shown that the ketogenic diet changes the composition and function of the gut microbiome in epilepsy patients.

The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy.

The gut microbiota has been linked to various neurological disorders via the gut-brain axis. Diet influences the composition of the gut microbiota. The ketogenic diet (KD) is a high-fat, adequate-protein, low-carbohydrate diet established for treatment of therapy-resistant epilepsy in children.

Thioredoxin glutathione reductase: its role in redox biology and potential as a target for drugs against neglected diseases.

Background: There are two, largely autonomous antioxidant pathways in many organisms, one based on thioredoxin and one based on glutathione, with each pathway having a unique flavoprotein oxidoreductase to maintain them in a reduced state. A recently discovered protein, thioredoxin glutathione reductase (TGR) potentially connects these two pathways. In a large group of parasitic worms, responsible for hundreds of millions of infections in humans and animals, untold morbidity and significant mortality, TGR is the sole enzyme present to maintain redox balance.

Inhibition of thioredoxin reductase 1 by porphyrins and other small molecules identified by a high-throughput screening assay.

The selenoprotein thioredoxin reductase 1 (TrxR1) has in recent years been identified as a promising anticancer drug target. A high-throughput assay for discovery of novel compounds targeting the enzyme is therefore warranted. Herein, we describe a single-enzyme, dual-purpose assay for simultaneous identification of inhibitors and substrates of TrxR1.

Noble metal targeting of thioredoxin reductase--covalent complexes with thioredoxin and thioredoxin-related protein of 14 kDa triggered by cisplatin.

Palladium (Pd), platinum (Pt), and gold (Au) are noble metals, two of which have established medical use. Pt has anticancer efficacy, predominantly as cisplatin, whereas the gold compound auranofin is used against arthritis. Both compounds inhibit the selenoprotein thioredoxin reductase (TrxR), but Pd has not been studied in this regard.

High levels of thioredoxin reductase 1 modulate drug-specific cytotoxic efficacy.

The selenoprotein thioredoxin reductase 1 (TrxR1) is currently recognized as a plausible anticancer drug target. Here we analyzed the effects of TrxR1 targeting in the human A549 lung carcinoma cell line, having a very high basal TrxR1 expression. We determined the total cellular TrxR activity to be 271.

Structure mechanism insights and the role of nitric oxide donation guide the development of oxadiazole-2-oxides as therapeutic agents against schistosomiasis.

Schistosomiasis is a chronic parasitic disease affecting hundreds of millions of individuals worldwide. Current treatment depends on a single agent, praziquantel, raising concerns of emergence of resistant parasites. Here, we continue our explorations of an oxadiazole-2-oxide class of compounds we recently identified as inhibitors of thioredoxin glutathione reductase (TGR), a selenocysteine-containing flavoenzyme required by the parasite to maintain proper cellular redox balance.

Cell death by SecTRAPs: thioredoxin reductase as a prooxidant killer of cells.

Background: SecTRAPs (selenium compromised thioredoxin reductase-derived apoptotic proteins) can be formed from the selenoprotein thioredoxin reductase (TrxR) by targeting of its selenocysteine (Sec) residue with electrophiles, or by its removal through C-terminal truncation. SecTRAPs are devoid of thioredoxin reductase activity but can induce rapid cell death in cultured cancer cell lines by a gain of function.

Principal Findings: Both human and rat SecTRAPs killed human A549 and HeLa cells.