Lusine Khachatryan

BACKGROUND: Several studies have highlighted the role of host-microbiome interactions in the pathogenesis of inflammatory bowel disease (IBD), resulting in an increasing amount of data mainly focusing on Western patients. Because of the increasing prevalence of IBD in newly industrialized countries such as those in Asia, the Middle East, and South America, there is mounting interest in elucidating the gut microbiota of these populations. We present a comprehensive analysis of several IBD-related biomarkers and gut microbiota profiles and functions of a unique population of patients with IBD and healthy patients from Kazan (Republic of Tatarstan, Russia). METHODS: Blood and fecal IBD biomarkers, serum cytokines, and fecal short-chain fatty acid (SCFA) content were profiled. Finally, fecal microbiota composition was analyzed by 16S and whole-genome shotgun sequencing. RESULTS: Fecal microbiota whole-genome sequencing confirmed the presence of classic IBD dysbiotic features at the phylum level, with increased abundance of Proteobacteria, Actinobacteria, and Fusobacteria and decreased abundance of Firmicutes, Bacteroidetes, and Verrucomicrobia. At the genus level, the abundance of both fermentative (SCFA-producing and hydrogen (H2)-releasing) and hydrogenotrophic (H2-consuming) microbes was affected in patients with IBD. This imbalance was confirmed by the decreased abundance of SCFA species in the feces of patients with IBD and the change in anaerobic index, which mirrors the redox status of the intestine. CONCLUSIONS: Our analyses highlighted how IBD-related dysbiotic microbiota-which are generally mainly linked to SCFA imbalance-may affect other important metabolic pathways, such as H2 metabolism, that are critical for host physiology and disease development.

The infant gut microbiota undergoes significant changes during early life, which are essential for immune system maturation, nutrient absorption, and metabolic programming. Among the various microbial metabolites, short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, produced through the fermentation of dietary fibers by gut bacteria, have emerged as critical modulators of host-microbiota interactions. SCFAs serve as energy sources for colonic cells and play pivotal roles in regulating immune responses, maintaining gut barrier integrity, and influencing systemic metabolic pathways. Recent research highlights the potential neuroprotective effects of SCFAs in pediatric populations. Disruptions in gut microbiota composition and SCFA production are increasingly associated with a range of pediatric health issues, including obesity, allergic disorders, inflammatory bowel disease (IBD), and neurodevelopmental disorders. This review synthesizes current knowledge on the role of microbiota-derived SCFAs in pediatric health, emphasizing their contributions from gut development to neuroprotection. It also underscores the need for further research to unravel the precise mechanisms by which SCFAs influence pediatric health and to develop targeted interventions that leverage SCFAs for therapeutic benefits.

We describe an open-source kPAL package that facilitates an alignment-free assessment of the quality and comparability of sequencing datasets by analyzing k-mer frequencies. We show that kPAL can detect technical artefacts such as high duplication rates, library chimeras, contamination and differences in library preparation protocols. kPAL also successfully captures the complexity and diversity of microbiomes and provides a powerful means to study changes in microbial communities. Together, these features make kPAL an attractive and broadly applicable tool to determine the quality and comparability of sequence libraries even in the absence of a reference sequence. kPAL is freely available at https://github.com/LUMC/kPAL webcite.

BACKGROUND: Fibrosis of extracellular matrix (ECM) in dilated cardiomyopathy (DCM) corresponds to the myocardial over-production of various types of collagens. However, mechanism of this process is poorly understood. OBJECTIVE: To investigate whether enhanced metabolism of ECM occur in DCM. METHODS: Seventy consecutive DCM patients (pts) (48 ± 12.1 years, EF 24.4 ± 7.4 %) and 20 healthy volunteers were studied. Based on symptoms duration, pts were divided into new-onset (n = 35, 6 months) and chronic DCM (n = 35, >6 months). Markers of collagen type I and III synthesis-procollagen type I carboxy- and amino-terminal peptides (PICP and PINP) and procollagen type III carboxy- and amino-terminal peptides (PIIICP and PIIINP), collagen 1 (col-1), ECM metabolism controlling factors-tumor growth factor beta-1 (TGF1-β), connective tissue growth factor (CTGF), and ECM degradation enzymes-matrix metalloproteinases (MMP-2, MMP-9) and their tissue inhibitor (TIMP-1) were measured in serum. All pts underwent right ventricular endomyocardial biopsy to study ECM fibrosis. RESULTS: The presence of fibrosis was detected in 24 (34.3 %) pts and was more prevalent in chronic DCM [17 (48.6 %) vs. 7 (20 %), p < 0.01]. The levels of PIIINP [4.41 (2.17-6.08) vs. 3.32 (1.69-5.02) ng/ml, p < 0.001], CTGF [3.82 (0.48-23.87) vs. 2.37 (0.51-25.32) ng/ml, p < 0.01], MMP-2 [6.06 (2.72-14.8) vs. 4.43 (2.27-7.4) ng/ml, p < 0.001], MMP-9 [1.98 (0.28-9.25) vs. 1.01 (0.29-3.59) ng/ml, p < 0.002)], and TIMP-1 [15.29 (1.8-36.17) vs. 2.61 (1.65-24.09) ng/ml, p < 0.004] were significantly higher in DCM, whereas levels of col-1 [57.7 (23.1-233.4) vs. 159.4 (31.2-512.9) pg/ml, p < 0.001] were significantly lower in DCM compared to controls. There were no differences in all measured serum markers of ECM metabolism between newonset and chronic DCM and as well as fibrosis positive and negative pts. Fibrosis was weakly correlated only with the duration of DCM (r = 0.23, p < 0.05), however, not a single serum marker of fibrosis correlated with fibrosis. Neither unadjusted nor adjusted models, constructed from serum markers of ECM metabolism, predicted the probability of myocardial fibrosis. CONCLUSIONS: Dynamics of ECM turnover in DCM is high, which is reflected by the increased levels CTGF and degradation enzymes. Synthesis of collagen type III prevailed over collagen type I. ECM metabolism was not different in DCM regardless of the duration of the disease and status of myocardial fibrosis. Serum markers of ECM metabolism were found not to be useful for the prediction of myocardial fibrosis in DCM.