Biology subjects

Knol, J.

Publications and source records attributed to Knol, J..

6 recordsLinked to original sources

bioRxiv2026

Taxon-in-context reveals ecological individuality in the human gut microbiome

Ecological theory holds that a microbe's role depends on its surrounding community. Yet abundance profiles and fixed ecological groupings leave its individual context implicit. We introduce taxon-in-context, a reproducible representation of each microbe's context within an individual's microbiome. Across 7,700 metagenomes, we show that common gut species occupy different contexts in different people. This flexibility peaked in early life and declined through adulthood, a pattern reproduced in a larger genus-level compendium. For selected species, context within each person's microbiome revealed age associations beyond species abundance and the person's context mixture. In an independent longitudinal urinary tract infection cohort, microbes switched contexts within individuals. Taxon-in-context enabled recurrence prediction where an abundance-based model performed near chance. Taxon-in-context and these findings expose a measurable, dynamic and individualized layer of microbiome organization, providing a basis for investigating why the same microbe or intervention may have different biological consequences across people.

systems biology↗

bioRxiv2025

A new role for lipoproteins LpqZ and FecB in orchestrating mycobacterial cell envelope biogenesis

Accounting for more deaths than any other bacterial species, Mycobacterium tuberculosis (Mtb) represents a critical threat to public health worldwide. A key factor contributing to Mtbs virulence is its unique cell envelope, which acts as a protective barrier. Among the components of this envelope, lipoproteins represent a critical but understudied group of proteins. In this study, we focused on 79 conserved putative lipoproteins, shared between Mtb and the closely related M. marinum. Leveraging the CRISPR1-Cas9 (Sth1Cas9) gene editing system for Mycobacteria, we generated frameshift mutations, targeting one conserved lipoprotein-coding gene at a time. We identified two mutants, lpqZ and fecB, that exhibited increased susceptibility to all tested antibiotics, suggesting essential roles in cell envelope biogenesis. Interestingly, despite having homology to periplasmic substrate binding proteins (SBPs), neither protein is associated with any inner membrane transporter complex. Instead, co-immunoprecipitation experiments revealed that LpqZ interacts with AftA and FecB interacts with AftB. Both these interaction partners are essential enzymes involved in arabinogalactan and lipoarabinomannan synthesis. Accordingly, we observed alterations for both glycoconjugates in lpqZ and fecB mutants. Together, these findings show that orphaned SBP-like proteins have been neofunctionalized in mycobacteria to aid key enzymes involved in cell envelope biosynthesis.

microbiology↗

bioRxiv2024

A three-country analysis of the gut microbiome indicates taxon associations with diet vary by location and strain

Emerging research suggests that diet plays a vital role in shaping the composition and function of the gut microbiota. While significant efforts have been made to identify general patterns linking diet to the gut microbiome, much of this research lacks representation from low- and middle-income countries such as Mexico. Additionally, both diet and the gut microbiome have highly complex and individualized configurations, and there is growing evidence that tailoring diets to individual gut microbiota profiles may optimize the path toward improving or maintaining health and preventing disease. Using fecal metagenomic data from 1,291 individuals across three countries, we examine two bacterial genera prevalent in the human gut, Prevotella and Faecalibacterium, which have gained significant attention due to their potential roles in human health. We find that they show significant associations with many aspects of diet, but that these associations vary in scale and direction, depending on the level of metagenomic resolution and the contextual population. These results highlight the growing importance of assembling metagenomic datasets that are standardized, comprehensive, and representative of diverse populations to increase our ability to tease apart the complex relationship between diet and the microbiome.

microbiology↗

bioRxiv2022

Quantitative physiology and proteome adaptations of Bifidobacterium breve NRBB57 at near-zero growth rates

In natural environments, nutrients are usually scarce causing microorganisms to grow slow while staying metabolically active. These natural conditions can be simulated using retentostat cultivations. The present study describes the physiological and proteome adaptations of the probiotic Bifidobacterium breve NRBB57 from high (0.4 h-1) to near-zero growth rates. Lactose-limited retentostat cultivations were carried out for 21 days in which the bacterial growth rate progressively reduced to 0.00092 h-1, leading to a 3.4-fold reduction of the maintenance energy requirement. Lactose was mainly converted into acetate, formate and ethanol at high growth rates while in the retentostat lactate production increased. Interestingly, the consumption of several amino acids (serine, aspartic acid and glutamine/arginine) and glycerol increased over time in the retentostat. Morphological changes and viable but non-culturable cells were also observed in the retentostat. Proteomes were compared for all growth rates, revealing a down-regulation of ribosomal proteins at near-zero growth rates and an up-regulation of proteins involved in the catabolism of alternative energy sources. Finally, we observed induction of the stringent response and stress defence systems. Retentostat cultivations were proven useful to study the physiology of B. breve, mimicking the nutrient scarcity of its complex habitat, the human gut. IMPORTANCEIn natural environments, nutrients are usually scarce causing microorganisms to grow slow while staying metabolically active. In this study we used retentostat cultivation to investigate how the probiotic Bifidobacterium breve adapts its physiology and proteome under severe nutrient limitation resulting in near-zero growth rates (<0.001 h-1). We showed that the nutrient limitation induced a multifaceted response including stress defence and stringent response, metabolic shifts and the activation of novel alternative energy producing pathways.

microbiology↗

bioRxiv2021

The role of the gut microbiota in the effects of early-life stress and dietary fatty acids on later-life central and metabolic outcomes in mice

Early-life stress (ELS) leads to increased vulnerability for mental and metabolic disorders. We have previously shown that dietary low {omega}-6/{omega}-3 polyunsaturated fatty acid (PUFA) ratio is able to protect against ELS-induced cognitive impairments. Due to the importance of the gut microbiota as determinants of long-term health, we here study the impact of ELS and dietary PUFAs on the gut microbiota, and how this relates to the previously described cognitive, metabolic and fatty acid profiles. Male mice were exposed to ELS via the limited bedding and nesting paradigm (postnatal day (P)2 - P9) and to an early diet (P2 - P42) with either high (15) or low (1) {omega}-6 linoleic acid to {omega}-3 alpha-linolenic acid ratio. 16S ribosomal RNA was sequenced and analyzed from fecal samples at P21, P42 and P180. ELS increased {beta}-diversity at P42, which persisted into adulthood. The low {omega}-6/{omega}-3 diet prevented the ELS-induced increase in {beta}-diversity, at P42. At the level of taxa abundance, for example, the abundance of the phyla Bacteroidetes increased while Actinobacteria and Verrucomicrobia decreased with age; ELS reduced the relative abundance of the genera RC9 gut group and Rikenella into adulthood and the low {omega}-6/{omega}-3 diet reduced the abundance of the Firmicutes Erysipelotrichia. At P42, species abundance correlated with body fat mass and circulating leptin (e.g. Bacteroidetes and Proteobacteria taxa) and fatty acid profiles (e.g. Firmicutes taxa). This study gives novel insights into the impact of age, ELS and dietary PUFAs on microbiota composition, providing potential targets for non-invasive (nutritional) modulation of the ELS-induced deficits. ImportanceEarly-life stress (ELS) leads to increased vulnerability to develop mental and metabolic disorders, however the biological mechanisms leading to such programming are not fully clear. Increased attention has been given to the importance of the gut microbiota as determinant of long term health and as potential target for non-invasive nutritional strategies to protect against the negative impact of ELS. Here we give novel insights in the complex interaction between ELS, early dietary {omega}-3 availability and the gut microbiota across ages and provides new potential targets for (nutritional) modulation of the long-term effects of the early-life environment via the microbiota.

microbiology↗

bioRxiv2018

Cross-feeding between Bifidobacterium infantis and Anaerostipes caccae on lactose and human milk oligosaccharides

The establishment of the gut microbiota immediately after birth is a dynamic process that may impact lifelong health. At this important developmental stage in early life, human milk oligosaccharides (HMOS) serve as specific substrates to promote the growth of gut microbes, particularly the group of Actinobacteria (bifidobacteria). Later in life, this shifts to the colonisation of Firmicutes and Bacteroidetes, which generally dominate the human gut throughout adulthood. The well-orchestrated transition is important for health, as an aberrant microbial composition and/or SCFA production are associated with colicky symptoms and atopic diseases in infants. Here, we study the trophic interactions between an HMOS-degrader, Bifidobacterium longum subsp. infantis and the butyrogenic Anaerostipes caccae using carbohydrate substrates that are relevant in this early life period, i.e. lactose and HMOS. Mono-and co-cultures of these bacterial species were grown at pH 6.5 in anaerobic bioreactors supplemented with lactose or total human milk carbohydrates (containing both lactose and HMOS). A cac was not able to grow on these substrates except when grown in co-culture with B. inf, leading concomitant butyrate production. Cross-feeding was observed, in which A. cac utilised the liberated monosaccharides as well as lactate and acetate produced by B. inf. This microbial cross-feeding is indicative of the key ecological role of bifidobacteria in providing substrates for other important species to colonise the infant gut. The symbiotic relationship between these key species contributes to the gradual production of butyrate early in life that could be important for host-microbial cross-talk and gut maturation.\n\nImportanceThe establishment of a healthy infant gut microbiota is crucial for the immune, metabolic and neurological development of infants. Recent evidence suggests that an aberrant gut microbiota early in life could lead to discomfort and predispose infants to the development of immune related diseases. This paper addresses the ecosystem function of two resident microbes of the infant gut. The significance of this research is the proof of cross-feeding interactions between HMOS-degrading bifidobacteria and a butyrate-producing microorganism. Bifidobacteria in the infant gut that support the growth and butyrogenesis of butyrate-producing bacteria, could orchestrated an important event of maturation for both the gut ecosystem and physiology of infant.

microbiology↗