Immuno-modulatory effect of probiotic E. coli Nissle 1917 in polarized human colonic cells against Campylobacter jejuni infection Original paper

What was studied?

This study examined the immunomodulatory effect of Escherichia coli Nissle 1917 in polarized human colonic cells against Campylobacter jejuni infection, focusing on how the probiotic reshapes epithelial innate responses and limits pathogen invasion and survival. The authors evaluated whether EcN pretreatment of polarized HT 29 cells reduces adhesion, invasion, and intracellular persistence of diverse C. jejuni strains and then profiled host antibacterial gene expression using a targeted RT2 PCR array. Because the focus keyphrase immuno modulatory effect of Escherichia coli Nissle 1917 appears here, the work is framed as an analysis of how EcN primes epithelial cells and alters key signaling pathways, such as NF kappa B, MAPK, and Akt, to create a protective microbiome-linked immune signature.

Who was studied?

The investigators used polarized human colorectal adenocarcinoma HT 29 cells as an in vitro model that closely mimics intestinal epithelium, including brush border, mucus production, tight junctions, and transepithelial resistance. These cells were infected with a wide panel of C. jejuni isolates from humans, poultry, turkeys, cattle, and starlings to capture host diverse strains with variable virulence and colonization properties. Escherichia coli Nissle 1917 served as the probiotic exposure and was applied to HT 29 monolayers before C. jejuni challenge, with conditions designed to test both early invasion at two hours and intracellular survival at twenty-four hours. For mechanistic analysis, the authors focused on a highly invasive reference strain, C. jejuni 81 176, and assessed changes in expression of one hundred and eighty-four antibacterial response genes, including cytokines, chemokines, pattern recognition receptors, and signaling intermediates in pathways relevant to epithelial barrier function and inflammation.

Most important findings

The study showed that the immunomodulatory effect of Escherichia coli Nissle 1917 profoundly altered the outcome of Campylobacter infection in polarized HT 29 cells. Pretreatment with EcN for four hours significantly reduced adhesion, invasion and intracellular survival of all tested C. jejuni strains, with some poultry and starling isolates showing complete clearance and no recoverable intracellular bacteria. For the 81 176 strain, EcN pretreatment achieved around ninety-three percent reduction in invasion and one hundred percent reduction in intracellular survival, indicating strong functional protection. Transcript profiling revealed that C. jejuni infection alone induced robust activation of NF kappa B signaling and upregulation of proinflammatory genes, including IL8, IL6, IL12B, IL18, TNF, and multiple chemokines, together with genes in TLR, NOD, and MAPK pathways, and promoted expression changes consistent with epithelial barrier disruption and apoptosis.

In contrast, EcN exposure without C. jejuni upregulated genes involved in cell growth, maintenance, proliferation, antimicrobial responses, and anti-inflammatory control, including regulators linked to Akt and PI3K signaling. When cells were pretreated with EcN and then infected, the expression of key proinflammatory mediators and upstream regulators, such as NF kappa B, TLR4, TLR5, TICAM1, TICAM2, NOD1, CASP8, IRAK3, JUN, and TRAF6, was markedly reduced compared with infection alone. At the same time, genes associated with anti-apoptotic and cytoprotective responses were favored. This pattern suggests that EcN primes epithelial innate immunity toward a balanced, protective state that limits pathogen-driven inflammation and supports barrier integrity.

Key implications

For clinicians, these findings indicate that the immunomodulatory effect of Escherichia coli Nissle 1917 extends beyond simple pathogen exclusion and involves active reprogramming of epithelial innate responses that may translate into reduced inflammation and tissue injury during Campylobacter infection. By dampening NF kappa B-driven cytokine storms while promoting Akt-mediated survival pathways, EcN appears to shift the mucosal environment toward a primed but controlled state that favors rapid pathogen clearance and preserves barrier function. From a microbiome signatures perspective, EcN carriage may mark a host with epithelial cells biased toward protective TLR and NOD signaling patterns and reduced susceptibility to Campylobacter-induced barrier disruption and apoptosis. These data support further evaluation of EcN as an antibiotic-sparing adjunct for Campylobacter-related gastroenteritis, and they also illustrate how probiotics can be characterized and selected based on defined transcriptional and signaling fingerprints in human intestinal models, rather than only on taxonomic identity or empirical clinical outcomes.