Lactobacillus acidophilus suppresses non-alcoholic fatty liver disease-associated hepatocellular carcinoma through producing valeric acid

Lau, Harry Cheuk-Hay; Zhang, Xiang; Ji, Fenfen; Lin, Yufeng; Liang, Wei; Li, Qing; Chen, Danyu; Fong, Winnie; Kang, Xing; Liu, Weixin; Chu, Eagle Siu-Hong; Ng, Queena Wing-Yin; Yu, Jun

doi:10.1016/j.ebiom.2023.104952

Cited by 22 publications

(3 citation statements)

References 35 publications

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“…HCC patients, characterized by significantly lower butyrate levels than HC, may benefit from butyrate supplementation to regulate intracellular calcium homeostasis and enhance anti-cancer treatment effectiveness [ 47 ]. Valproic acid, produced by Lactobacillus acidophilus , binds to the GPR41/43 receptor on liver cell surfaces, inhibiting the oncogenic Rho-GTPase pathway and exhibiting protection against non-alcoholic fatty liver disease-related HCC [ 48 ]. In our study, the addition of L. brevis SR52-2 and L. delbrueckii Q80 for fermentation significantly increased valeric acid concentration in the HCC group, suggesting a potential regulatory effect on valeric acid production.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Lactic Acid Bacteria Anti-Hepatitis B Virus (HBV) Effect and Modulation of the Intestinal Microbiota in Fecal Cultures from HBV-Associated Hepatocellular Carcinoma Patients

Yang,

Gao,

Zhang

et al. 2024

Nutrients

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Hepatocellular carcinoma (HCC), being ranked as the top fifth most prevalent cancer globally, poses a significant health challenge, with a considerable mortality rate. Hepatitis B virus (HBV) infection stands as the primary factor contributing to HCC, presenting substantial challenges in its treatment. This study aimed to identify lactic acid bacteria (LAB) with anti-HBV properties and evaluate their impact on the intestinal flora in HBV-associated HCC. Initially, two LAB strains, Levilactobacillus brevis SR52-2 (L. brevis SR52-2) and LeviLactobacillus delbrueckii subsp. bulgaicus Q80 (L. delbrueckii Q80), exhibiting anti-HBV effects, were screened in vitro from a pool of 498 LAB strains through cell experiments, with extracellular expression levels of 0.58 ± 0.05 and 0.65 ± 0.03, respectively. These strains exhibited the capability of inhibiting the expression of HBeAg and HBsAg. Subsequent in vitro fermentation, conducted under simulated anaerobic conditions mimicking the colon environment, revealed a decrease in pH levels in both the health control (HC) and HCC groups influenced by LAB, with a more pronounced effect observed in the HC group. Additionally, the density of total short-chain fatty acids (SCFAs) significantly increased (p < 0.05) in the HCC group. Analysis of 16S rRNA highlighted differences in the gut microbiota (GM) community structure in cultures treated with L. brevis SR52-2 and L. delbrueckii Q80. Fecal microflora in normal samples exhibited greater diversity compared to HBV-HCC samples. The HCC group treated with LAB showed a significant increase in the abundance of the phyla Firmicutes, Bacteroidetes and Actinobacteria, while Proteobacteria significantly decreased compared to the untreated HCC group after 48 h. In conclusion, the findings indicate that LAB, specifically L. brevis SR52-2 and L. delbrueckii Q80, possessing antiviral properties, contribute to an improvement in gastrointestinal health.

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Section: Discussionmentioning

confidence: 99%

In Vitro Lactic Acid Bacteria Anti-Hepatitis B Virus (HBV) Effect and Modulation of the Intestinal Microbiota in Fecal Cultures from HBV-Associated Hepatocellular Carcinoma Patients

Yang,

Gao,

Zhang

et al. 2024

Nutrients

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“…As a member of the Lactobacillus family of Gram-positive bacilli, L. acidophilus is widely acknowledged and recognized as a potent probiotic for the small intestine. Numerous investigations have demonstrated that L. acidophilus has anti-inflammatory ( Li S. C. et al, 2019 ; Li W. Q. et al, 2019 ), anti-oxidation ( Zhang et al, 2021 ), anti-tumor ( Lau et al, 2024 ), improves hypertension ( Romão da Silva et al, 2020 ), improves cardiovascular disease ( Chen et al, 2013 ), protects intestinal mucosal barrier ( Lightfoot et al, 2015 ), and a wide variety of other pharmacological effects. The results of non-target metabolomics showed that compared with the 0 h group, telmisartan, vitamin C, glutamine, carvedilol, Dl-lactate, and other substances in the culture supernatant of L. acidophilus increased significantly after 24 h of proliferation in vitro .…”

Section: Discussionmentioning

confidence: 99%

Analysis of the anti-PCV2 mechanism of Lactobacillus acidophilus based on non-target metabolomics and high-throughput molecular docking

Cao,

Ling,

Haseeb

et al. 2024

Front. Microbiol.

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Our previous studies have revealed that L. acidophilus possesses inhibitory effects on PCV2 proliferation in vivo, although the underlying mechanisms remain elusive. Probiotics like L. acidophilus are known to exert antiviral through their metabolites. Therefore, in this study, non-targeted metabolomics was used to detect the changes in metabolites of L. acidophilus after 24 h of proliferation. Subsequently, high-throughput molecular docking was utilized to analyze the docking scores of these metabolites with PCV2 Cap and Rep, aiming to identify compounds with potential anti-PCV2 effects. The results demonstrated that 128 compounds such as Dl-lactate were significantly increased. The results of high-throughput molecular docking indicated that compounds such as ergocristine, and telmisartan formed complexes with Cap and Rep, suggesting their potential anti-PCV2 properties. Furthermore, compounds like vitamin C, exhibit pharmacological effects consistent with L. acidophilus adding credence to the idea that L. acidophilus may exert pharmacological effects through its metabolites. These results will provide a foundation for the study of L. acidophilus.

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“…B. theta also increased liver and intestinal folate levels, hepatic metabolites, and the percentage of polyunsaturated fatty acids in the liver, offering a widely reported benefit for improving NAFLD [279]. In mice with NAFLD-HCC, the supplementation of Lactobacillus acidophilus, through the action of the metabolite valeric acid, which binds to the hepatocyte surface GPR41/43 receptor to inhibit the Rho-GTPase pathway, inhibited NAFLD-HCC [280]. Likewise, the acetate secreted by Bifidobacterium pseudolongum, and reaching the liver via the portal vein, has a protective role in NAFLD-HCC progression and can therefore be thought of as a potential new probiotic [173].…”

Section: Fmt In Hepatic and Pancreatic Disease: Clinical Trialsmentioning

confidence: 97%

Gut–Liver–Pancreas Axis Crosstalk in Health and Disease: From the Role of Microbial Metabolites to Innovative Microbiota Manipulating Strategies

Marroncini,

Naldi,

Martinelli

et al. 2024

Biomedicines

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The functions of the gut are closely related to those of many other organs in the human body. Indeed, the gut microbiota (GM) metabolize several nutrients and compounds that, once released in the bloodstream, can reach distant organs, thus influencing the metabolic and inflammatory tone of the host. The main microbiota-derived metabolites responsible for the modulation of endocrine responses are short-chain fatty acids (SCFAs), bile acids and glucagon-like peptide 1 (GLP-1). These molecules can (i) regulate the pancreatic hormones (insulin and glucagon), (ii) increase glycogen synthesis in the liver, and (iii) boost energy expenditure, especially in skeletal muscles and brown adipose tissue. In other words, they are critical in maintaining glucose and lipid homeostasis. In GM dysbiosis, the imbalance of microbiota-related products can affect the proper endocrine and metabolic functions, including those related to the gut–liver–pancreas axis (GLPA). In addition, the dysbiosis can contribute to the onset of some diseases such as non-alcoholic steatohepatitis (NASH)/non-alcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC), and type 2 diabetes (T2D). In this review, we explored the roles of the gut microbiota-derived metabolites and their involvement in onset and progression of these diseases. In addition, we detailed the main microbiota-modulating strategies that could improve the diseases’ development by restoring the healthy balance of the GLPA.

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Lactobacillus acidophilus suppresses non-alcoholic fatty liver disease-associated hepatocellular carcinoma through producing valeric acid

Cited by 22 publications

References 35 publications

In Vitro Lactic Acid Bacteria Anti-Hepatitis B Virus (HBV) Effect and Modulation of the Intestinal Microbiota in Fecal Cultures from HBV-Associated Hepatocellular Carcinoma Patients

In Vitro Lactic Acid Bacteria Anti-Hepatitis B Virus (HBV) Effect and Modulation of the Intestinal Microbiota in Fecal Cultures from HBV-Associated Hepatocellular Carcinoma Patients

Analysis of the anti-PCV2 mechanism of Lactobacillus acidophilus based on non-target metabolomics and high-throughput molecular docking

Gut–Liver–Pancreas Axis Crosstalk in Health and Disease: From the Role of Microbial Metabolites to Innovative Microbiota Manipulating Strategies

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