Emerging evidence shows that modulation of the microbiome can suppress
intra-abdominal hypertension (IAH)-induced intestinal barrier damage through the regulation of
amino acid (AA) biosynthesis. Here, we investigated the protective effects of orally gavaged Lactobacillus acidophilus L-92 (L92) and a mixture of AA in rats with induced IAH. The results showed that both L92 and AA pretreatments effectively mitigated IAH-induced intestinal damage. Interestingly, L92 but not AA prevented metagenomic changes induced by IAH. Bacteroides fragilis, Bacteroides eggerthii, Bacteroides ovatus, Faecalibacterium prausnitzii, Prevotella, and extensively altered functional pathways were associated with L92-mediated host protection. Metabolomic profiling revealed that
tryptophan metabolism was involved in both L92- and AA-mediated gut protection. The
tryptophan metabolite 5-hydroxyindoleacetic
acid (5-HIAA) is a sensitive
biomarker for IAH in rats and patients with either gut-derived
sepsis (n = 41) or all-source
sepsis (n = 293). In conclusion, we show that microbiome and metabolic modulations can effectively prevent IAH-induced intestinal damage and that
5-HIAA is a potential metabolic marker for IAH and
sepsis. IMPORTANCE Gut protection through modulation of the microbiome for
critically ill patients has been gaining much attention recently.
Intra-abdominal hypertension (IAH) is a prevailing clinical feature of acute gastrointestinal
injuries in
critically ill patients, characterized by nonspecific intestinal barrier damage. Prolonged IAH can induce or aggravate the development of
sepsis and multiorgan dysfunctions. Therefore, the prevention of IAH-induced damage in rats through microbiome and metabolic interventions by commercially available L92 and AA treatments and the identification of
5-HIAA as an important marker for IAH/
sepsis have important clinical implications for the treatment and early diagnosis of
critically ill patients.