Biology subjects

Holmberg, S.

Publications and source records attributed to Holmberg, S..

4 recordsLinked to original sources

bioRxiv2025

Systematic profiling of growth interactions in human gut microbiome species

Microbial interactions shape the composition and stability of the human gut microbiome. Yet, the molecular mechanisms underlying these relationships remain poorly understood. Here, we systematically profiled 1,224 pairwise growth interactions among 36 representative gut bacterial strains using a spent medium assay. Most interactions were inhibitory and largely explained by resource depletion or medium acidification. We investigated further the molecular basis of a positive interaction, showing that Clostridium perfringens promotes the growth of Mediterraneibacter gnavus through extracellular vesicles. Additionally, we identified Veillonella parvula as a key species capable of modulating environmental pH, thereby enabling the growth of Parabacteroides merdae, a strain highly sensitive to acidic conditions. This pH-buffering effect was enhanced by guanine supplementation and persisted in multi-species communities containing different pH-lowering strains from diverse bacterial phyla. This demonstrates the ecological relevance of V. parvula, a species that, despite being commonly present in human gut microbiomes, is generally found at low levels. Overall, the comprehensive dataset and mechanistic insights presented here provide a foundation for rational strategies to manipulate microbiome composition and function.

microbiology↗

bioRxiv2025

A molecular circuit regulates fate plasticity in emerging and adult AT2 cells

Alveolar AT1 and AT2 cells are vital for lung gas exchange and become compromised in several diseases. While key differentiation signals are known, their emergence and fate plasticity are unclear. Here we show in the embryonic lung that single AT2s emerge at intermediate zones, extrude, and connect with nearby epithelium via interlumenal junctioning. We observe that AT2s retain fate plasticity until the bZIP transcription factor C/EBP suppresses Notch signaling at a novel Dlk1 enhancer. Both Dlk1 and Cebpa are regulated by the polycomb repressive complex (PRC2), which together form a "pulse generator" circuit that times Dlk1 expression and thus Notch activation, resulting in a "salt and pepper" pattern of AT1 and AT2 fate. In injured adult lungs, C/EBP downregulation is required to re-access AT2 fate plasticity and is mediated by the dominant negative C/EBP family member CHOP. Finally, Cebpa loss also activates a "defender" AT2 state, distinct from its reparative state, and we propose AT2s toggle between either state following infection to protect and repair alveoli.

developmental biology↗

bioRxiv2020

Calprotectin modulates inflammatory collateral tissue damage during intraperitoneal origin systemic candidiasis

Peritonitis is a leading cause of severe sepsis in surgical intensive care units, as over 70% of patients diagnosed with peritonitis develop septic shock. A critical role of the immune system is to return to homeostasis after combating infection. S100A8/A9 (calprotectin) is an antimicrobial, pro-inflammatory protein complex often used as a biomarker for diagnosis of disease activities in many inflammatory disorders. Here we describe the role of S100A8/A9 on inflammatory collateral tissue damage (ICTD). We performed an in vivo Candida albicans disseminated peritonitis mouse model using WT and S100A9-deficient mice and stimulated primary macrophages with recombinant S100A8/A9 in the presence or absence of the compound paquinimod, a specific inhibitor of S100A9. In addition, the effects on ICTD and fungal clearance were investigated. S100A9-deficient mice developed less ICTD than wildtype mice. Restoration of S100A8/A9 in S100A9 knockout mice resulted in increased ICTD and fungal clearance comparable to wildtype levels. Treatment with paquinimod abolished ICTD. The data indicated that S100A8/A9 controls ICTD levels and host antimicrobial modulation at a systemic level during intra-abdominal candidiasis (IAC).

immunology↗

bioRxiv2019

Using Chaos for Facile High-throughput Fabrication of Ordered Multilayer Micro- and Nanostructures

This paper introduces the concept of continuous chaotic printing, i.e., the use of chaotic flows for deterministic and continuous fabrication of fibers with internal multilayered micro-or nanostructures. Two free-flowing materials are coextruded through a printhead containing a miniaturized Kenics static mixer (KSM) composed of multiple helicoidal elements. This produces a fiber with a well-defined internal multilayer microarchitecture at high speeds (>1.0 m min-1). The number of mixing elements and the printhead diameter determine the number and thickness of the internal lamellae, which are generated according to successive bifurcations that yield a vast amount of inter-material surface area (~102 cm2 cm3) and high resolution features (~10 m). In an exciting further development, we demonstrate a scale-down of the microstructure by 3 orders of magnitude, to the nanoscale level (~10 nm), by feeding the output of a continuous chaotic 3D printhead into an electrospinner. Comparison of experimental and computational results demonstrates the robust and predictable output and performance of continuous chaotic 3D printing. The simplicity and high resolution of continuous chaotic printing strongly supports its potential use in novel applications, including--but not limited to--bioprinting of multi-scale tissue-like structures, modeling of bacterial communities, and fabrication of smart multi-material and multilayered constructs.

bioengineering↗