The lipopeptide iturin from Bacillus subtilis has been found to have a potential inhibitory effect on breast cancer, alveolar adenocarcinoma, renal carcinoma, and colon adenocarcinoma. In this study, the potential of B. subtilis lipopeptides (a mixture of iturin homologues, concentration of 42.75%) to inhibit chronic myelogenous leukemia was evaluated using K562 myelogenous leukemia cells. The results showed that the lipopeptides could completely inhibit the growth of K562 at 100 μM, with an IC50 value of 65.76 μM. The lipopeptides inhibited the profile of K562 via three pathways: (1) induction of paraptosis indicated by the occurrence of cytoplasmic vacuoles, and swelling of the mitochondria and endoplasmic reticulum (ER) without membrane blebbing in the presence of a caspase inhibitor; (2) inhibition of autophagy progress illustrated by the upregulated expression of LCII and P62; and (3) induction of apoptosis by causing ROS burst, and induction of the intrinsic pathway indicated by the upregulated expression of cytochrome c (Cyto-c), bax, and bad, together with downregulated expression of Bcl-2. The ROS-dependent apoptosis and caspase-independent paraptosis were verified using the ROS inhibitor and caspase inhibitor, respectively. The extrinsic apoptosis pathway was not involved in the lipopeptide’s effects on K562. Overall, the B. subtilis lipopeptides (consisting of a majority of iturin) exhibited promising potential in inhibiting chronic myelogenous leukemia in vitro via simultaneously causing paraptosis, apoptosis, and inhibition of autophagy.

Gut microbiota imbalance is one of the major causes of ulcerative colitis (UC). L. rhamnosus SHA113 (LRS), a strain isolated from healthy human milk, influences the regulation of gut flora. This study aims to determine whether this strain can ameliorate UC by modulating gut microbiota. Mouse models of UC were established using C57BL/6Cnc mice with intragastric administration of 3.0% (w/v) dextran sodium sulfate (DSS). LRS was used to treat the mouse models of UC with 10⁹ cfu mL⁻¹ cell suspension via intragastric administration. To verify the effect of gut microbiota on UC, fecal microbiota collected from the mice after the treatment with LRS were also used to treat the UC mouse models (FMT). The severity of UC was evaluated based on body weight, colon length, disease activity index (DAI), and hematoxylin–eosin staining. The microbial composition was analyzed by 16S rRNA sequencing. The mRNA expression levels of cytokines, mucins, tight junction proteins, and antimicrobial peptides in the gastrointestinal tract were detected by quantitative real-time polymerase chain reaction. The short-chain fatty acid (SCFAs) in the cecal contents of all mice were quantitatively detected by gas chromatography and mass spectrometry. Both LRS and FMT exerted excellent therapeutic effects on UC, as evidenced by the reduction in body weight loss, colon length, and colon structural integrity, as well as the increase in the DAI (disease activity index). LRS and FMT treatments showed similar effects: (1) an increase of total SCFA production in the cecal contents and the abundance of gut microbial diversity and flora composition; (2) decreases in two genera (Parabacteroides and Escherichia/Shigella) related to the DAI and the enhancement of SCFAs and IL-10 positively related genera in the gut microbiota (Bilophila, Roseburia, Akkermansia, and Bifidobacterium); (3) downregulation of the expression of tumor necrosis factor-α, interleukin IL-6, and IL-1β, and upregulation of the expression of the anti-inflammatory cytokine IL-10; and (4) upregulation of the expression of mucins (Muc1–4) and tight junction protein ZO-1. Overall, L. rhamnosus SHA113 relieves UC via the regulation of gut microbiota: increases in SCFA-producing genera and decreases in UC-related genera. In addition, a single strain is sufficient to induce a significant change in the gut microbiota and exert therapeutic effects on UC.

Deoxynivalenol (DON) is a mycotoxin that contaminates grains and feed. Degradation and toxicity reduction of DON by probiotics benefit human and animal health. Lactobacillus rhamnosus is an FDA-approved probiotic that can be used in children. After screening seven L. rhamnosus strains isolated from human milk, SHA113 showed the highest DON degradation rate of 60% under the optimal conditions of 37 °C, pH 6.0, OD₆₀₀ = 1.5, 5 mg L⁻¹ DON, and 48 h. When dead and live SHA113 cells were used separately, only the live cells reduced the DON concentration and transformed it into 3-epi-DON. Mice feeding experiments showed that pretreatment with SHA113 for 48 h reduced the toxicity of DON to the immunological system and organs. Directly feeding SHA113 cells could also slightly reduce the DON toxicity. Both in vitro and in vivo experiments indicated that L. rhamnosus has potential to reduce DON toxicity.