Biology subjects

Lal, C. V.

Publications and source records attributed to Lal, C. V..

3 recordsLinked to original sources

bioRxiv2026

Functional Equivalence of Heat-Inactivated (HI) and Live Probiotic RSB11 in Suppressing Inflammation: Expanding Formulation and Application Potential

The clinical potential of probiotics has been widely recognized, but their translation into reliable therapeutic products has been hindered by major limitations such as undesirable immunogenic responses, the need to maintain viability, instability during storage and transport, and concerns regarding safety in vulnerable populations. Postbiotics, defined as inanimate microbial cells or their components with pro-health activities, overcome many of these limitations by offering enhanced stability, reproducibility, and safety. However, it is very vital to understand if the heat inactivation (conversion of a probiotic to its postbiotic inert form) compromise its functional efficacy. Here, we systematically compared a novel probiotic-derived candidate, Lactiplantibacillus plantarum RSB11 strain, in its live (RSB11 Life, probiotic) and heat-inactivated (RSB11-HI, postbiotic) forms across multiple human epithelial and non-epithelial models relevant to inflammation driven pathologies. To investigate the gut-tissue(s)-axis concept we used gut (Caco-2), lung (HBE), ovary (BG1), bone (osteoblasts, MG-63), kidney (A-498) and liver (HepG2) cells exposed to E-coli or lipopolysaccharide (LPS), and quantified matrix metalloproteinase-9 (MMP-9), an inflammatory mediator, by qPCR and pro-inflammatory cytokines such as tumor necrosis factor- (TNF-), IL-6, and IL-1{beta} by ELISA. In addition, we assessed {beta}-glucuronidase activity and estrogen modulation to explore gut-ovarian axis signaling. Across all models, both RSB11 Life and RSB11-HI robustly suppressed MMP-9, TNF-, IL-6 and IL-1{beta} induction, with equivalent magnitude of effect. The inactivated form retained full cytokine-suppressive capacity and, notably, enhanced {beta}-glucuronidase activity, suggesting additional benefits in microbiome hormone cross-talk. Our findings demonstrate that heat inactivation does not compromise, and may even expand, the functional range of RSB11. By maintaining bioactivity while eliminating the drawbacks of live biotics, heat inactivated RSB11 emerges as a robust, scalable, and versatile postbiotic with potential applications in systemic inflammatory disorders. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/705228v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@7bb1e6org.highwire.dtl.DTLVardef@dc86c7org.highwire.dtl.DTLVardef@147448org.highwire.dtl.DTLVardef@de5232_HPS_FORMAT_FIGEXP M_FIG C_FIG Graphical abstract of RSB11-HI activityHeat-inactivated postbiotic RSB11-HI retains the anti-inflammatory efficacy of its live counterpart (RSB11Life) across diverse organ-relevant cell models. Upon LPS or E-coli stimulation, epithelial, immune, and tissue-specific cells (gut, lung, ovary, bone, kidney, liver) upregulate pro-inflammatory mediators including MMP-9, TNF-, IL-6, and IL-1{beta}. Both RSB11Life and RSB11-HI effectively suppress these inflammatory responses, with RSB11-HI exhibiting more consistent and robust reductions of inflammatory markers across models. Additionally, RSB11-HI uniquely enhances {beta}-glucuronidase activity, facilitating estrogen metabolism and signaling through the gut-ovary axis. Together, these findings highlight RSB11-HI as a stable, safe, and multifunctional postbiotic candidate suitable for therapeutic formulation. Image was designed using ChatGPT.

immunology↗

bioRxiv2023

Antimicrobial peptides modulate pulmonary inflammation by altering the intestinal microbiota

Mammalian mucosal barriers secrete antimicrobial peptides (AMPs) as critical host-derived regulators of the microbiota. However, mechanisms that support homeostasis of the microbiota in response to inflammatory stimuli such as supraphysiologic oxygen remain unclear. Here, we show that neonatal mice breathing supraphysiologic oxygen or direct exposure of intestinal organoids to supraphysiologic oxygen suppress the intestinal expression of AMPs and alters the composition of the intestinal microbiota. Oral supplementation of the prototypical AMP lysozyme to hyperoxia exposed neonatal mice reduced hyperoxia-induced alterations in their microbiota and was associated with decreased lung injury. Our results identify a gut-lung axis driven by intestinal AMP expression and mediated by the intestinal microbiota that is linked to lung injury. Together, these data support that intestinal AMPs modulate lung injury and repair. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=185 SRC="FIGDIR/small/529700v2_ufig1.gif" ALT="Figure 1"> View larger version (66K): org.highwire.dtl.DTLVardef@800123org.highwire.dtl.DTLVardef@1caac5forg.highwire.dtl.DTLVardef@faa875org.highwire.dtl.DTLVardef@49c4e9_HPS_FORMAT_FIGEXP M_FIG C_FIG In BriefUsing a combination of murine models and organoids, Abdelgawad and Nicola et al. find that suppression of antimicrobial peptide release by the neonatal intestine in response to supra-physiological oxygen influences the progression of lung injury likely via modulation of the ileal microbiota. HighlightsO_LISupraphysiologic oxygen exposure alters intestinal antimicrobial peptides (AMPs). C_LIO_LIIntestinal AMP expression has an inverse relationship with the severity of lung injury. C_LIO_LIAMP-driven alterations in the intestinal microbiota form a gut-lung axis that modulates lung injury. C_LIO_LIAMPs may mediate a gut-lung axis that modulates lung injury. C_LI

microbiology↗

bioRxiv2023

Neutrophilic Inflammation in Models of Bronchopulmonary Dysplasia and Chronic Obstructive Pulmonary Disease is Rescued by a Lactobacilli Based Live Biotherapeutic

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity. Exposure to noxious stimuli such as hyperoxia, volutrauma, and infection in infancy can have long-reaching impacts on lung health and predispose towards the development of conditions such as chronic obstructive pulmonary disease (COPD) in adulthood. BPD and COPD are both marked by lung tissue degradation, neutrophil influx, and decreased lung function. Both diseases also express a change in microbial signature dominated by Proteobacteria abundance and Lactobacillus scarcity. However, the relationship between pulmonary microbial dysbiosis and the mechanisms of downstream disease development has yet to be elucidated. We hypothesized that a double-hit hyperoxia and LPS murine model of BPD would show heightened Ac-PGP pathway and neutrophil activity. Through gain- and loss-of-function studies in the same model we showed that Ac-PGP plays a critical role in driving BPD development. We tested a novel inhaled live biotherapeutic using active Lactobacillus strains to counteract lung dysbiosis in in vitro and in vivo models of BPD and COPD. The Lactobacillus LBP is effective in improving lung structure and function, reducing neutrophil influx, and reducing a broad swath of pro-inflammatory markers in these models of chronic pulmonary disease. Live inhaled microbiome-based therapeutics show promise in addressing common pathways of disease progression that in the future can be targeted in a variety of chronic lung diseases.

microbiology↗