| Summary: | An experiment was conducted to evaluate the effects of the Micro-Aid Liquid 10 (MAL10) (DPI Global, Porterville, CA, USA), a product made from yucca extract, on growth performance, gut microbiota, and resistance of white shrimp, <i>Litopenaeus vannamei</i> against infectious disease caused by <i>Vibrio alginolyticus</i>. MAL10 was added to shrimp rearing water at different levels of 0 (control), 0.25 mL m<sup>3−1</sup> (W0.25), 0.5 mL m<sup>3−1</sup> (W0.5), 1 mL m<sup>3−1</sup> (W1), and 5 mL m<sup>3−1</sup> (W5), respectively, once per week for 70 days. Growth performances, including final body weight, specific growth rate, average daily growth and percentage of weight gain, were significantly improved by adding the MAL10 at levels up to 5 mL m<sup>3−1</sup>, which may be due to the proliferation of B cells in hepatopancreas of MAL10-treated shrimp. No significant differences in the total viable count and <i>Vibrio</i>-like count in the gut of shrimp were recorded by spread plate method. In the challenge test, shrimp reared in the water supplemented with MAL10 at levels of 1–5 mL m<sup>3−1</sup> had significantly lower cumulative mortality after a challenge test with <i>V. alginolyticus</i> compared to shrimp reared in the control, W0.25 and W0.5 groups. Next-generation sequencing indicated that the relative distribution of phylum Proteobacteria in control (80.4%) was higher than the W (77.4%). The proportion of <i>Vibrio</i> was primarily dominant genera in the shrimp intestine and highest in the control group compared to the W group, followed by <i>Spongiimonas</i>, <i>Motilimonas, Demequina</i>, and <i>Shewanella</i> genera. Although there was no statistically significant difference, higher α-diversity indices were recorded in the W5-treated group than in the control group. Therefore, it is considered that MAL10 could be used as a natural alternative in shrimp aquaculture to reduce the risk of infectious disease caused by pathogenic <i>Vibrio</i> and improve the growth performance of white shrimp.
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