Biology subjects

Beraza, N.

Publications and source records attributed to Beraza, N..

3 recordsLinked to original sources

bioRxiv2025

Microbial oral-gut translocation in advanced chronic liver disease is linked to exacerbation of intestinal barrier dysfunction and hepatic fibrosis

While microbiome perturbations are associated with advanced chronic liver disease (ACLD), microbial disease mechanisms are poorly understood. Using multi-omics analyses of paired saliva and faecal samples from an ACLD cohort, we identified next-to-identical oral and gut bacterial strains (including Veillonella and Streptococcus spp.) which increased in absolute abundance in the gut of ACLD patients. These translocators uniquely encoded a collagenase-like proteinase (prtC) with the potential for gut barrier disruption and prtC faecal abundance was a robust ACLD biomarker (auPR=0.91). CCl4-treated mice inoculated with Veillonella and Streptococcus prtC-encoding patient isolates showed exacerbation of gut barrier impairment and hepatic fibrosis. Furthermore, faecal collagenase activity was increased in ACLD patients and experimentally confirmed for the prtC gene from translocating Veillonella parvula. Overall, our study establishes mechanistic links between oral-gut translocation and ACLD pathobiology, and identifies the oral microbiome as an important contributing factor with potential for microbial diagnostics and therapeutics.

microbiology↗

bioRxiv2024

Low protein diet protects liver function upon Salmonella infection by metabolic reprogramming of macrophages

Background & AimsWestern diets are the underlying cause of metabolic and liver diseases. Recent trend to limit the consumption of protein-rich animal products has become more prominent. This dietary change entails decreased protein consumption; however, it is still unknown how this affects innate immunity. Here, we studied the influence of a low protein diet (LPD) on the liver response to bacterial infection. MethodsMice were fed a LPD and exposed to Salmonella enterica serotype Typhimurium infection. Mechanistic studies were done in vitro where bone marrow derived macrophages were cultured in a low-aa media to mimic in vivo reduction of protein availability and challenged with bacterial endotoxin. ResultsWe found that a LPD protects from S Typhimurium-induced liver damage. Bulk- and 10xsingle cell-RNA sequencing of liver tissues and isolated immune cells showed reduced activation of myeloid cells in mice fed with LPD after S Typhimurium infection. Mechanistically, we found reduced activation of the mammalian target of rapamycin (mTOR) pathway whilst increased phagocytosis and activation of autophagy in LPD-programmed macrophages. Dietary restoration of leucine reverted the protective effects of a LPD and restored the damaging effects of Salmonella on liver parenchyma in mice. ConclusionsLow protein diet protects the liver form S Typhimurium-induced tissue damage via modulating macrophage autophagy and phagocytosis. Our result support the causal role of dietary components on the fitness of the immune system. SYNOPSISLow protein diet protects the liver from Salmonella-mediated liver injury that associates with reduced mTOR activation and increased autophagy in macrophages. Restoration of the mTOR pathway with aminoacid supplementation reverses the protection of a low protein diet from Salmonella-liver damage.

immunology↗

bioRxiv2022

A novel bacteriocin produced by Bifidobacterium longum subsp. infantis has dual antimicrobial and immunomodulatory activity

Bacteriocins are ribosomally-synthesized antimicrobial peptides produced by bacteria with either narrow or broad spectrum activity. Many genome mining studies have indicated that bacteriocin gene clusters are widespread within certain gut microbiota members. In early life, Bifidobacterium comprise the dominant microbiota genus in vaginally delivered and breast-fed infants, with high levels associated with improved health. However, in many cases the mechanisms underlying these beneficial effects are unknown, although a limited number of studies have suggested that bacteriocin production by Bifidobacterium may represent a key mechanism for preventing pathogen over-growth. Here, we used BAGEL4 and antiSMASH to identify putative bacteriocin sequences in the whole genome sequences of 33 Bifidobacterium strains isolated from infants participating in two clinical studies. We identified a novel non-lantibiotic bacteriocin from Bifidobacterium longum subsp. infantis LH_664, with 40% sequence homology to Lactococcin 972 from Lactococcus lactis subsp. lactis. The putative bacteriocin (Bifidococcin_664) was chemically synthesized and studied for antimicrobial and immune-modulatory activities. We determined it has discrete activity against Clostridium perfringens and it appears to have novel immune stimulatory activities, promoting macrophage phagocytosis and specific cytokine release. These data highlight strain-specific beneficial properties in the early life genus Bifidobacterium, and suggest avenues for development of novel and highly specific dual action antimicrobials, and possible probiotic strains, that are active against clinically important bacterial pathogens. Data summarySamples LH_9 to LH_666 were previously sequenced and deposited to ENA under accession numbers ERS2658025-ERS2658043. Samples LH_986 to LH_1052 are newly sequenced and deposited to NCBI under accession numbers SAMN24838598-SAMN24838611. Additionally, previously assembled publicly available sequences (n=7) were retrieved online from NCBI Genomes database. See Supplementary Table S1 for further details.

microbiology↗