High alkalinity is the most important limiting factor in carbonate-type saline–alkali water aquaculture, and fish growth is slow and survival is low in highly alkaline environments. Selenium-enriched (Se-enriched) Lactobacillus plantarum (L. plantarum) has antioxidant and anti-inflammatory properties and can regulate the balance of the gut flora. However, the physiological regulatory mechanism of Se-enriched L. plantarum on common carp under high alkalinity stress is still unclear. In the present study, 360 common carp were randomly divided into a control group, a high alkalinity group, and a Se-enriched L. plantarum and high alkalinity group and fed for 56 days. High alkalinity stress induced growth inhibition in common carp. Histopathology revealed atrophy of the intestinal villi and damage to the intestinal microvilli and tight junction complexes. Serological parameters showed that the serum ammonia and LPS contents were significantly increased. Gut microbial disruption under high alkalinity stress increased the abundance of Bacteroidota (LPS-producing bacteria), Providencia sp. (ammonia-producing bacteria) and Vibrio (pathogenic bacteria) and significantly decreased the expression of the tight junction proteins Zonula occludens-1 (ZO-1) and Occludin, disrupting the gut barrier. However, Se-enriched L. plantarum decreased the abundance of Bacteroidota Providencia sp. and Vibrio, increased the expression of the tight junction proteins ZO-1 and Occludin, and alleviated intestinal damage caused by high alkalinity while reducing the content of lipopolysaccharides (LPS) and ammonia in the serum. In addition, metabolomic analysis of serum revealed that high alkalinity stress activated autophagy, glucocorticoids and mineralocorticoid receptor agonists/antagonists, ABC transporters, the phosphatidylinositol signalling system, and the Mammalian Target of Rapamycin (mTOR) signalling pathway and significantly increased creatine content and riboflavin. Se-enriched L. plantarum treatment significantly decreased the creatine and D-alanine contents. In summary, this study revealed that Se-enriched L. plantarum can alleviate the harmful effects of high alkalinity on common carp by regulating the balance of the intestinal microbiota, improving intestinal barrier function, reducing the amount of harmful substances entering the bloodstream, and regulating blood metabolites. This study demonstrates the physiological regulatory mechanism of Se-enriched L. plantarum in alleviating high alkalinity stress and provides ideas and a theoretical basis for the protection against high alkalinity poisoning of fish in saline–alkali waters.
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