Prevention of Severe Intestinal Barrier Dysfunction Through a Single-Species Probiotics is Associated With the Activation of Microbiome-Mediated Glutamate-Glutamine Biosynthesis

Introduction: Intra-abdominal hypertension (IAH), the leading complication in the intensive care unit, significantly disturbs the gut microbial composition by decreasing the relative abundance of Lactobacillus and increasing the relative abundance of opportunistic infectious bacteria.

Methods: To evaluate the preventative effect of Lactobacillus-based probiotics on IAH-induced intestinal barrier damages, a single-species probiotics (L92) and a multispecies probiotics (VSL#3) were introduced orally to Sprague-Dawley rats for 7 days before inducing IAH. The intestinal histology and permeability to macromolecules (fluoresceine isothiocyanate, FITC-dextran, N = 8 for each group), the parameters of immunomodulatory and oxidative responses [monocyte chemotactic protein 1 (MCP-1), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-10 (IL-10), malonaldehyde, glutathione peroxidase (GSH- Px), catalase (CAT), and superoxide dismutase; N = 4 for each group], and the microbiome profiling (N = 4 for each group) were analyzed.

Results: Seven-day pretreatments of L92 significantly alleviated the IAH-induced increase in intestinal permeability to FITC-dextran and histological damage (P < 0.0001), accompanied with the suppression of inflammatory and oxidative activation. The increase of MCP-1 and IL-1β was significantly inhibited (P < 0.05); the anti-inflammatory cytokines, IL-4, and IL-10 were maintained at high levels; and the suppression of CAT (P < 0.05) was significantly reversed when pretreated with L92. On the contrary, no significant protective effects were observed in the VSL#3-pretreated group. Among the 84 identified species, 260 MetaCyc pathways, and 217 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, the protective effects of L92 were correlated with an increased relative abundance of Bacteroides finegoldii, Odoribacter splanchnicus, and the global activation of amino acid biosynthesis pathways, especially the glutamate-glutamine biosynthesis pathway.

Conclusions: Seven-day pretreatment with a single-species probiotics can prevent IAH-induced severe intestinal barrier dysfunction, potentially through microbial modulation.