Probiotics have shown potential in managing hypercholesterolemia and related metabolic conditions. This study evaluated the effects of Lactocaseibacillus (Lactobacillus) paracasei sup. paracasei TISTR 2593 on the gut microbiome and metabolic health in patients with hypercholesterolemia, and was registered in the Thai Clinical Trial Registry (TCTR 20220917002). In a randomized, double-blind, placebo-controlled trial, 22 hypercholesterolemic participants received either the probiotic or a placebo daily for 90 days. Fecal samples collected before and after the intervention revealed significant microbiome changes, including a decrease in Subdoligranulum, linked to rheumatoid arthritis, and an increase in Flavonifractor, known for its anti-inflammatory properties. Additionally, the probiotic group exhibited a significant reduction in low-density lipoprotein cholesterol (LDL-C) levels. These findings suggest that L. paracasei TISTR 2593 can modulate the gut microbiome and improve metabolic health, warranting further investigation into its mechanisms and long-term benefits.

Amphotericin B deoxycholate (AmpB) is used for the treatment of leishmaniasis caused by Leishmania (Mundinia) martiniquensis in Thailand, and relapse cases have been documented. To date, genomic analysis of drug-resistant L. martiniquensis strains is limited. In this study, comparative genome analyses were performed with an experimentally selected AmpB-resistant L. martiniquensis (AmpBRP2i) and two cryopreserved L. martiniquensis parasite strains isolated from a patient showing differences in response to AmpB treatment, LSCM1-WT (susceptible) and LSCM1-6 (resistant). Applying the GIP genome analyses package, we identified aneuploidy and gene copy number variations in all three samples, none of which correlated with AmpB resistance. In contrast, single nucleotide variant (SNV) analyses revealed an SNV in AmpB-resistant strains introduced a premature stop codon into a putative sterol C-24 reductase gene (C24R) (LSCM1_02556) involved in the ergosterol biosynthetic pathway in Leishmania. As Leishmania AmpB resistance has previously been linked to mutations in other genes of the ergosterol biosynthesis pathway in different species of Leishmania parasites, these results suggest that C24R may serve as an additional marker of AmpB resistance in Leishmania. We further identified two missense SNVs in AmpB-resistant strains in a putative 'ABC transporter-like/ABC transporter family' gene (LSCM1_01856) that could be involved in drug efflux. These initial findings pave the way for future research with a larger number of isolates to confirm the genomic signature we associate here with AmpB resistance.

Background/Objectives: Obesity and its metabolic comorbidities, including dyslipidemia and non-alcoholic fatty liver disease (NAFLD), are a growing global health burden, and current pharmacotherapies have limited efficacy and notable adverse effects. The gut microbiome has emerged as a key regulator of host metabolism, and its dysregulation is implicated in obesity. This study investigated the therapeutic potential of Piper sarmentosum Roxb. aqueous extract (PSRW) on metabolic dysfunction and gut microbiota composition in a high-fat diet (HFD)-induced obese rat model. Methods: HFD-induced obese male Wistar rats received PSRW, simvastatin, or their combination for 12 weeks. Serum lipids (TC, TG, HDL, LDL), liver enzymes (AST, ALT), and renal markers were measured, and gut microbiota were profiled by 16S rRNA (V4) sequencing with PICRUSt2/KEGG functional prediction. The phenolic composition of the same extract was characterized by HPLC in a companion study. Results: PSRW did not cause weight loss but significantly lowered serum TC, AST, and ALT, with efficacy comparable to simvastatin and significantly lower TG than control, though not significantly different from HFD. Co-administration of PSRW and simvastatin produced a greater reduction in TC and liver enzymes than either agent alone. HFD shifted microbial community structure and enriched pro-inflammatory phyla such as Desulfobacterota; PSRW partially reversed these changes, suppressing obesogenic Lachnospiraceae genera while enriching beneficial microbes including Dwaynesavagella, and functionally reprogrammed taxa such as Kineothrix and Muribaculum from detrimental to protective associations. HFD enriched microbial glycosphingolipid biosynthesis, whereas the PSRW simvastatin combination uniquely enhanced glycine, serine, and threonine metabolism. Conclusions:P. sarmentosum extract ameliorates HFD-induced dyslipidemia and hepatotoxicity, and these effects are accompanied by remodeling of the composition and predicted functional capacity of the gut microbiome. Its ability to act in combination with statins highlights its potential as a candidate complementary therapy for hyperlipidemia and NAFLD.

Background/Objectives: Relapse remains the leading cause of mortality in pediatric acute lymphoblastic leukemia (ALL), underscoring the need for novel biomarkers and therapies. The objective of this study is to identify distinct metabolomes associated with relapsed ALL, using bone marrow aspirated at the relapse episode itself, a specimen that is rarely banked and whose metabolome has not previously been reported. Method: This study utilized untargeted liquid chromatography–mass spectrometry (LC-MS) metabolomics on bone marrow aspirates from 21 children with B-lineage ALL. Aliquots from the 12 non-relapsed patients were collected at initial diagnosis and those from the 9 relapsed patients at relapse, so group and disease phase are collinear by design. Results: The resulting metabolic profile clearly distinguished bone marrow sampled at relapse from bone marrow sampled at initial diagnosis. Partial least-squares discriminant analysis separated the two groups, completely in positive ion mode and with 18 of 21 samples correctly classified in negative ion mode (1000-permutation test, p = 0.001 in both modes), and 31 of 92 metabolites in positive ion mode and 3 of 44 in negative ion mode differed after Benjamini–Hochberg correction (q < 0.05), of which 26 and 3 respectively also exceeded the fold-change threshold of |log2FC| > 1. The relapse-associated differences involved carnitine, amino acid and lipid metabolites. O-acetylcarnitine was elevated, which is compatible with increased fatty acid oxidation; dipeptides were higher but not significantly (q = 0.075); L-allo-threonine was elevated, which is compatible with increased flux through the serine–glycine one-carbon pathway; adenosine monophosphate (AMP) was decreased, although the abundance of AMP alone does not provide the AMP: adenosine triphosphate (ATP) ratio and cannot establish the activity of AMP-activated protein kinase (AMPK) or of mammalian target of rapamycin complex 1 (mTORC1); and individual lipid species differed in both directions. These are hypotheses generated by the observed differences in metabolite abundance and are not mechanisms demonstrated by this study. Conclusions: This exploratory comparison describes the metabolite composition of bone marrow at relapse and identifies fatty acid oxidation, the serine–glycine one-carbon pathway and ether-lipid metabolism as priorities for future investigation rather than as established therapeutic dependencies. Because the relapsed specimens were obtained at relapse, the signature describes relapsed disease and is not evidence that relapse can be predicted at diagnosis.