During oxidative stress, an important factor in the development of many diseases, cellular oxidative and antioxidant activities are imbalanced due to various internal and external factors such as inflammation or diet. The administration of probiotic Lactobacillus strains has been shown to confer a range of antibacterial, anti-inflammatory, antioxidant, and immunomodulatory effects in the host. This review focuses on the potential role of oxidative stress in inflammatory bowel diseases (IBD), cancer, and liver-related diseases in the context of preventive and therapeutic effects associated with Lactobacillus. This article reviews studies in cell lines and animal models as well as some clinical population reports that suggest that Lactobacillus could alleviate basic symptoms and related abnormal indicators of IBD, cancers, and liver damage, and covers evidence supporting a role for the Nrf2, NF-κB, and MAPK signaling pathways in the effects of Lactobacillus in alleviating inflammation, oxidative stress, aberrant cell proliferation, and apoptosis. This review also discusses the unmet needs and future directions in probiotic Lactobacillus research including more extensive mechanistic analyses and more clinical trials for Lactobacillus-based treatments.

Lysosomes are membrane-bound organelles with an acidic lumen and are traditionally characterized as a recycling center in cells. Lysosomal ion channels are integral membrane proteins that form pores in lysosomal membranes and allow the influx and efflux of essential ions. Transmembrane protein 175 (TMEM175) is a unique lysosomal potassium channel that shares little sequence similarity with other potassium channels. It is found in bacteria, archaea, and animals. The prokaryotic TMEM175 consists of one six-transmembrane domain that adopts a tetrameric architecture, while the mammalian TMEM175 is comprised of two six-transmembrane domains that function as a dimer in lysosomal membranes. Previous studies have demonstrated that the lysosomal K⁺ conductance mediated by TMEM175 is critical for setting membrane potential, maintaining pH stability, and regulating lysosome–autophagosome fusion. AKT and B-cell lymphoma 2 regulate TMEM175’s channel activity through direct binding. Two recent studies reported that the human TMEM175 is also a proton-selective channel under normal lysosomal pH (4.5–5.5) as the K⁺ permeation dramatically decreased at low pH while the H⁺ current through TMEM175 greatly increased. Genome-wide association studies and functional studies in mouse models have established that TMEM175 is implicated in the pathogenesis of Parkinson’s disease, which sparks more research interests in this lysosomal channel.

Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD), arises from intricate interactions involving genetics, environment, and pharmaceuticals with an ambiguous pathogenic mechanism. Recently, there has been an increasing utilization of lactic acid bacteria (LAB) in managing IBD, attributed to their ability to enhance intestinal barrier function, mitigate inflammatory responses, and modulate gut microbiota. This review initiates by elucidating the pathogenesis of IBD and its determinants, followed by an exploration of the mechanisms underlying LAB therapy in UC and CD. Special attention is directed towards their influence on intestinal barrier function and homeostasis regulated by gut microbiota. Furthermore, the review investigates the complex interplay among pivotal gut microbiota, metabolites, and pathways associated with inflammation. Moreover, it underscores the limitations of LAB in treating IBD, particularly in light of their varying roles in UC and CD. This comprehensive analysis endeavors to offer insights for the optimized application of LAB in IBD therapy.

Polysaccharides derived from plants, algae, or fungi serve as the major components of some human diets. Polysaccharides have been shown to exhibit diverse biological activities in improving human health, and have also been proposed to function as potent modulators of gut microbiota composition, thus playing a bi-directional regulatory role in host health. Here, we review a variety of polysaccharide structures potentially linked to biological functions, and cover current research progress in characterizing their pharmaceutical effects in various disease models, including antioxidant, anticoagulant, anti-inflammatory, immunomodulatory, hypoglycemic, and antimicrobial activities. We also highlight the effects of polysaccharides on modulating gut microbiota via enrichment for beneficial taxa and suppression of potential pathogens, leading to increased microbial expression of carbohydrate-active enzymes and enhanced short chain fatty acid production. This review also discusses polysaccharide-mediated improvements in gut function by influencing interleukin and hormone secretion in host intestinal epithelial cells.

Probiotic supplementation is a key therapeutic strategy for promoting gut health and maintaining gut homeostasis by modulating functional microbiota. In this study, we isolated two lactic acid bacteria (LAB) strains, Pediococcus pentosaceus TCM-3 and Lacticaseibacillus paracasei TDM-2, from Qinghai-Tibetan plateau, and evaluated their probiotic properties and antioxidant bioactivity. In which, TDM-2 had higher T-AOC activity than either TCM-3 or LGG (4.10 μmol/mL vs. 3.68 and 3.53 μmol/mL, respectively, p < 0.05). These strains have shown high antioxidant activity compared to the LAB strains and were found to be acid and bile salt tolerant, confronting the safety issues of antibiotic resistance and the capability of surviving in simulated gastric and intestinal juices. In vitro fermentation experiments with human gut microbiota revealed significant differences in microbial community composition between samples supplemented with TCM-3 and TDM-2 and those without. The addition of these two strains resulted in an enrichment of beneficial taxa, such as the Pediococcus, Lactobacillus, and Clostridium_sensu_strictos at the genus level, and Firmicutes and Proteobacteria at the phylum level. Notably, the TCM-3 group exhibited higher short-chain fatty acid production than the TDM-2 group and untreated controls (acetic acid at 12 h: 4.54 mmol L⁻¹ vs. 4.06 mmol L⁻¹ and 4.00 mmol L⁻¹; acetic acid at 24 h: 4.99 mmol L⁻¹ vs. 4.90 mmol L⁻¹ and 4.82 mmol L⁻¹, p < 0.05). These findings demonstrate that LAB supplementation with high antioxidant capacity and probiotic properties can promote gut health by modulating functional microbiota and is enriching for beneficial taxa. Our study provides guidance for therapeutic strategies that use novel LAB strains to maintain gut homeostasis and functional microbiota modulation.

The human brain is highly dependent on oxygen, utilizing approximately 20% of the body’s oxygen at rest. Oxygen deprivation to the brain can lead to loss of consciousness within seconds and death within minutes. Recent studies have identified regions of the brain with spontaneous episodic hypoxia, referred to as “hypoxic pockets”. Hypoxia can also result from impaired blood flow due to conditions such as heart disease, blood clots, stroke, or hemorrhage, as well as from reduced oxygen intake or excessive oxygen consumption caused by factors like low ambient oxygen, pulmonary diseases, infections, inflammation, and cancer. Severe hypoxia in the brain can manifest symptoms similar to Parkinson’s disease (PD), including cerebral edema, mood disturbances, and cognitive impairments. Additionally, the development of PD appears to be closely associated with hypoxia and hypoxic pathways. This review seeks to investigate the molecular interactions between hypoxia and PD, emphasizing the pathological role of hypoxic pathways in PD and exploring their potential as therapeutic targets.