Stress-sensitive neural circuits change the gut microbiome via duodenal glands.

Negative psychological states impact immunity by altering the gut microbiome. However, the relationship between brain states and microbiome composition remains unclear. We show that Brunner's glands in the duodenum couple stress-sensitive brain circuits to bacterial homeostasis. Brunner's glands mediated the enrichment of gut Lactobacillus species in response to vagus nerve stimulation. Cell-specific ablation of the glands markedly suppressed Lactobacilli counts and heightened vulnerability to infection. In the forebrain, we mapped a vagally mediated, polysynaptic circuit connecting the central nucleus of the amygdala to Brunner's glands. Chronic stress suppressed central amygdala activity and phenocopied the effects of gland lesions. Conversely, excitation of either the central amygdala or parasympathetic vagal neurons activated Brunner's glands and reversed the effects of stress on the gut microbiome and immunity. The findings revealed a tractable brain-body mechanism linking psychological states to host defense.

Vaginal Lactobacillus fatty acid response mechanisms reveal a metabolite-targeted strategy for bacterial vaginosis treatment.

Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the vaginal microbiota and enhances bacterial fitness by biochemically sequestering OA in a derivative form only ohyA-harboring organisms can exploit. OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro BV model, suggesting a metabolite-based treatment approach.

Bronze Age cheese reveals human-Lactobacillus interactions over evolutionary history.

Despite the long history of consumption of fermented dairy, little is known about how the fermented microbes were utilized and evolved over human history. Here, by retrieving ancient DNA of Bronze Age kefir cheese (∼3,500 years ago) from the Xiaohe cemetery, we explored past human-microbial interactions. Although it was previously suggested that kefir was spread from the Northern Caucasus to Europe and other regions, we found an additional spreading route of kefir from Xinjiang to inland East Asia. Over evolutionary history, the East Asian strains gained multiple gene clusters with defensive roles against environmental stressors, which can be a result of the adaptation of Lactobacillus strains to various environmental niches and human selection. Overall, our results highlight the role of past human activities in shaping the evolution of human-related microbes, and such insights can, in turn, provide a better understanding of past human behaviors.

Microbial metabolite enhances immunotherapy efficacy by modulating T cell stemness in pan-cancer.

The immune checkpoint blockade (ICB) response in human cancers is closely linked to the gut microbiota. Here, we report that the abundance of commensal Lactobacillus johnsonii is positively correlated with the responsiveness of ICB. Supplementation with Lactobacillus johnsonii or tryptophan-derived metabolite indole-3-propionic acid (IPA) enhances the efficacy of CD8+ T cell-mediated αPD-1 immunotherapy. Mechanistically, Lactobacillus johnsonii collaborates with Clostridium sporogenes to produce IPA. IPA modulates the stemness program of CD8+ T cells and facilitates the generation of progenitor exhausted CD8+ T cells (Tpex) by increasing H3K27 acetylation at the super-enhancer region of Tcf7. IPA improves ICB responsiveness at the pan-cancer level, including melanoma, breast cancer, and colorectal cancer. Collectively, our findings identify a microbial metabolite-immune regulatory pathway and suggest a potential microbial-based adjuvant approach to improve the responsiveness of immunotherapy.

Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment.

The use of probiotics by cancer patients is increasing, including among those undergoing immune checkpoint inhibitor (ICI) treatment. Here, we elucidate a critical microbial-host crosstalk between probiotic-released aryl hydrocarbon receptor (AhR) agonist indole-3-aldehyde (I3A) and CD8 T cells within the tumor microenvironment that potently enhances antitumor immunity and facilitates ICI in preclinical melanoma. Our study reveals that probiotic Lactobacillus reuteri (Lr) translocates to, colonizes, and persists within melanoma, where via its released dietary tryptophan catabolite I3A, it locally promotes interferon-γ-producing CD8 T cells, thereby bolstering ICI. Moreover, Lr-secreted I3A was both necessary and sufficient to drive antitumor immunity, and loss of AhR signaling within CD8 T cells abrogated Lr's antitumor effects. Further, a tryptophan-enriched diet potentiated both Lr- and ICI-induced antitumor immunity, dependent on CD8 T cell AhR signaling. Finally, we provide evidence for a potential role of I3A in promoting ICI efficacy and survival in advanced melanoma patients.

Microbiota-Derived Lactate Activates Production of Reactive Oxygen Species by the Intestinal NADPH Oxidase Nox and Shortens Drosophila Lifespan.

Commensal microbes colonize the gut epithelia of virtually all animals and provide several benefits to their hosts. Changes in commensal populations can lead to dysbiosis, which is associated with numerous pathologies and decreased lifespan. Peptidoglycan recognition proteins (PGRPs) are important regulators of the commensal microbiota and intestinal homeostasis. Here, we found that a null mutation in Drosophila PGRP-SD was associated with overgrowth of Lactobacillus plantarum in the fly gut and a shortened lifespan. L. plantarum-derived lactic acid triggered the activation of the intestinal NADPH oxidase Nox and the generation of reactive oxygen species (ROS). In turn, ROS production promoted intestinal damage, increased proliferation of intestinal stem cells, and dysplasia. Nox-mediated ROS production required lactate oxidation by the host intestinal lactate dehydrogenase, revealing a host-commensal metabolic crosstalk that is probably broadly conserved. Our findings outline a mechanism whereby host immune dysfunction leads to commensal dysbiosis that in turn promotes age-related pathologies.

The Microbial Metabolite Butyrate Stimulates Bone Formation via T Regulatory Cell-Mediated Regulation of WNT10B Expression.

Nutritional supplementation with probiotics can prevent pathologic bone loss. Here we examined the impact of supplementation with Lactobacillus rhamnosus GG (LGG) on bone homeostasis in eugonadic young mice. Micro-computed tomography revealed that LGG increased trabecular bone volume in mice, which was due to increased bone formation. Butyrate produced in the gut following LGG ingestion, or butyrate fed directly to germ-free mice, induced the expansion of intestinal and bone marrow (BM) regulatory T (Treg) cells. Interaction of BM CD8+ T cells with Treg cells resulted in increased secretion of Wnt10b, a bone anabolic Wnt ligand. Mechanistically, Treg cells promoted the assembly of a NFAT1-SMAD3 transcription complex in CD8+ cells, which drove expression of Wnt10b. Reducing Treg cell numbers, or reconstitution of TCRß-/- mice with CD8+ T cells from Wnt10b-/- mice, prevented butyrate-induced bone formation and bone mass acquisition. Thus, butyrate concentrations regulate bone anabolism via Treg cell-mediated regulation of CD8+ T cell Wnt10b production.

Intestinal Lactobacillus murinus-derived small RNAs target porcine polyamine metabolism.

Gut microbiota plays a vital role in host metabolism; however, the influence of gut microbes on polyamine metabolism is unknown. Here, we found germ-free models possess elevated polyamine levels in the colon. Mechanistically, intestinal Lactobacillus murinus-derived small RNAs in extracellular vesicles down-regulate host polyamine metabolism by targeting the expression of enzymes in polyamine metabolism. In addition, Lactobacillus murinus delays recovery of dextran sodium sulfate-induced colitis by reducing polyamine levels in mice. Notably, a decline in the abundance of small RNAs was observed in the colon of mice with colorectal cancer (CRC) and human CRC specimens, accompanied by elevated polyamine levels. Collectively, our study identifies a specific underlying mechanism used by intestinal microbiota to modulate host polyamine metabolism, which provides potential intervention for the treatment of polyamine-associated diseases.

Resistance to host antimicrobial peptides mediates resilience of gut commensals during infection and aging in Drosophila.

Resilience to short-term perturbations, like inflammation, is a fundamental feature of microbiota, yet the underlying mechanisms of microbiota resilience are incompletely understood. Here, we show that Lactiplantibacillus plantarum, a major Drosophila commensal, stably colonizes the fruit fly gut during infection and is resistant to Drosophila antimicrobial peptides (AMPs). By transposon screening, we identified L. plantarum mutants sensitive to AMPs. These mutants were impaired in peptidoglycan O-acetylation or teichoic acid D-alanylation, resulting in increased negative cell surface charge and higher affinity to cationic AMPs. AMP-sensitive mutants were cleared from the gut after infection and aging-induced gut inflammation in wild-type, but not in AMP-deficient flies, suggesting that resistance to host AMPs is essential for commensal resilience in an inflamed gut environment. Thus, our work reveals that in addition to the host immune tolerance to the microbiota, commensal-encoded resilience mechanisms are necessary to maintain the stable association between host and microbiota during inflammation.

Redefining the bacteriophage mv4 site-specific recombination system and the sequence specificity of its attB and core-attP sites.

Through their involvement in the integration and excision of a large number of mobile genetic elements, such as phages and integrative and conjugative elements (ICEs), site-specific recombination systems based on heterobivalent tyrosine recombinases play a major role in genome dynamics and evolution. However, despite hundreds of these systems having been identified in genome databases, very few have been described in detail, with none from phages that infect Bacillota (formerly Firmicutes). In this study, we reanalyzed the recombination module of Lactobacillus delbrueckii subsp. bulgaricus phage mv4, previously considered atypical compared with classical systems. Our results reveal that mv4 integrase is a 369 aa protein with all the structural hallmarks of recombinases from the Tn916 family and that it cooperatively interacts with its recombination sites. Using randomized DNA libraries, NGS sequencing, and other molecular approaches, we show that the 21-bp core-attP and attB sites have structural similarities to classical systems only if considering the nucleotide degeneracy, with two 7-bp inverted regions corresponding to mv4Int core-binding sites surrounding a 7-bp strand-exchange region. We also examined the different compositional constraints in the core-binding regions, which define the sequence space of permissible recombination sites.

Diverse mechanisms control amino acid-dependent environmental alkalization by Candida albicans.

Candida albicans has the capacity to neutralize acidic growth environments by releasing ammonia derived from the catabolism of amino acids. The molecular components underlying alkalization and its physiological significance remain poorly understood. Here, we present an integrative model with the cytosolic NAD+-dependent glutamate dehydrogenase (Gdh2) as the principal ammonia-generating component. We show that alkalization is dependent on the SPS-sensor-regulated transcription factor STP2 and the proline-responsive activator Put3. These factors function in parallel to derepress GDH2 and the two proline catabolic enzymes PUT1 and PUT2. Consistently, a double mutant lacking STP2 and PUT3 exhibits a severe alkalization defect that nearly phenocopies that of a gdh2-/- strain. Alkalization is dependent on mitochondrial activity and in wild-type cells occurs as long as the conditions permit respiratory growth. Strikingly, Gdh2 levels decrease and cells transiently extrude glutamate as the environment becomes more alkaline. Together, these processes constitute a rudimentary regulatory system that counters and limits the negative effects associated with ammonia generation. These findings align with Gdh2 being dispensable for virulence, and based on a whole human blood virulence assay, the same is true for C. glabrata and C. auris. Using a transwell co-culture system, we observed that the growth and proliferation of Lactobacillus crispatus, a common component of the acidic vaginal microenvironment and a potent antagonist of C. albicans, is unaffected by fungal-induced alkalization. Consequently, although Candida spp. can alkalinize their growth environments, other fungal-associated processes are more critical in promoting dysbiosis and virulent fungal growth.

An insight into the gut microbiota after Schistosoma japonicum eggs immunization in an experimental ulcerative colitis model.

Schistosome infection and schistosome-derived products have been implicated in the prevention and alleviation of inflammatory bowel disease by manipulating the host immune response, whereas the role of gut microbiota in this protective effect remains poorly understood. In this study, we found that the intraperitoneal immunization with Schistosoma japonicum eggs prior to dextran sulfate sodium (DSS) application significantly ameliorated the symptoms of DSS-induced acute colitis, which was characterized by higher body weight, lower disease activity index score and macroscopic inflammatory scores. We demonstrated that the immunomodulatory effects of S. japonicum eggs were accompanied by an influence on gut microbiota composition, abundance, and diversity, which increased the abundance of genus Turicibacter, family Erysipelotrichaceae, phylum Firmicutes, and decreased the abundance of genus Odoribacter, family Marinifilaceae, order Bacteroidales, class Bacteroidia, phylum Bacteroidota. In addition, Lactobacillus was identified as a biomarker that distinguishes healthy control mice from DSS-induced colitis mice. The present study revealed the importance of the gut microbiota in S. japonicum eggs exerting protective effects in an experimental ulcerative colitis (UC) model, providing an alternative strategy for the discovery of UC prevention and treatment drugs.

Lactobacillus delbrueckii alleviates lipopolysaccharide-induced muscle inflammation and atrophy in weaned piglets associated with inhibition of endoplasmic reticulum stress and protein degradation.

Pro-inflammatory cytokines in muscle play a pivotal role in physiological responses and in the pathophysiology of inflammatory disease and muscle atrophy. Lactobacillus delbrueckii (LD), as a kind of probiotics, has inhibitory effects on pro-inflammatory cytokines associated with various inflammatory diseases. This study was conducted to explore the effect of dietary LD on the lipopolysaccharide (LPS)-induced muscle inflammation and atrophy in piglets and to elucidate the underlying mechanism. A total of 36 weaned piglets (Duroc × Landrace × Large Yorkshire) were allotted into three groups with six replicates (pens) of two piglets: (1) Nonchallenged control; (2) LPS-challenged (LPS); (3) 0.2% LD diet and LPS-challenged (LD+LPS). On d 29, the piglets were injected intraperitoneally with LPS or sterilized saline, respectively. All piglets were slaughtered at 4 h after LPS or saline injection, the blood and muscle samples were collected for further analysis. Our results showed that dietary supplementation of LD significantly attenuated LPS-induced production of pro-inflammatory cytokines IL-6 and TNF-α in both serum and muscle of the piglets. Concomitantly, pretreating the piglets with LD also clearly inhibited LPS-induced nuclear translocation of NF-κB p65 subunits in the muscle, which correlated with the anti-inflammatory effects of LD on the muscle of piglets. Meanwhile, LPS-induced muscle atrophy, indicated by a higher expression of muscle atrophy F-box, muscle RING finger protein (MuRF1), forkhead box O 1, and autophagy-related protein 5 (ATG5) at the transcriptional level, whereas pretreatment with LD led to inhibition of these upregulations, particularly genes for MuRF1 and ATG5. Moreover, LPS-induced mRNA expression of endoplasmic reticulum stress markers, such as eukaryotic translational initiation factor 2α (eIF-2α) was suppressed by pretreatment with LD, which was accompanied by a decrease in the protein expression levels of IRE1α and GRP78. Additionally, LD significantly prevented muscle cell apoptotic death induced by LPS. Taken together, our data indicate that the anti-inflammatory effect of LD supply on muscle atrophy of piglets could be likely regulated by inhibiting the secretion of pro-inflammatory cytokines through the inactivation of the ER stress/NF-κB singling pathway, along with the reduction in protein degradation.

Lactobacillus casei-fermented Amomum xanthioides ameliorates metabolic dysfunction in high-fat diet-induced obese mice.

Amomum xanthioides (AX) has been used as an edible herbal medicine to treat digestive system disorders in Asia. Additionally, Lactobacillus casei is a well-known probiotic commonly used in fermentation processes as a starter. The current study aimed to investigate the potential of Lactobacillus casei-fermented Amomum xanthioides (LAX) in alleviating metabolic disorders induced by high-fat diet (HFD) in a mouse model. LAX significantly reduced the body and fat weight, outperforming AX, yet without suppressing appetite. LAX also markedly ameliorated excessive lipid accumulation and reduced inflammatory cytokine (IL-6) levels in serum superior to AX in association with UCP1 activation and adiponectin elevation. Furthermore, LAX noticeably improved the levels of fasting blood glucose, serum insulin, and HOMA-IR through positive regulation of glucose transporters (GLUT2, GLUT4), and insulin receptor gene expression. In conclusion, the fermentation of AX demonstrates a pronounced mitigation of overnutrition-induced metabolic dysfunction, including hyperlipidemia, hyperglycemia, hyperinsulinemia, and obesity, compared to non-fermented AX. Consequently, we proposed that the fermentation of AX holds promise as a potential candidate for effectively ameliorating metabolic disorders.

Involvement of the gut microbiota in cancer cachexia.

Cancer cachexia, or the unintentional loss of body weight in patients with cancer, is a multiorgan and multifactorial syndrome with a complex and largely unknown etiology; however, metabolic dysfunction and inflammation remain hallmarks of cancer-associated wasting. Although cachexia manifests with muscle and adipose tissue loss, perturbations to the gastrointestinal tract may serve as the frontline for both impaired nutrient absorption and immune-activating gut dysbiosis. Investigations into the gut microbiota have exploded within the past two decades, demonstrating multiple gut-tissue axes; however, the link between adipose and skeletal muscle wasting and the gut microbiota with cancer is only beginning to be understood. Furthermore, the most used anticancer drugs (e.g. chemotherapy and immune checkpoint inhibitors) negatively impact gut homeostasis, potentially exacerbating wasting and contributing to poor patient outcomes and survival. In this review, we 1) highlight our current understanding of the microbial changes that occur with cachexia, 2) discuss how microbial changes may contribute to adipose and skeletal muscle wasting, and 3) outline study design considerations needed when examining the role of the microbiota in cancer-induced cachexia.

Study on the alleviative effect of Lactobacillus plantarum on Eimeria falciformis infection.

Coccidia of the genus Eimeria are specialized intracellular parasitic protozoa that cause severe coccidiosis when they infect their hosts. Animals infected with Eimeria develop clinical symptoms, such as anorexia, diarrhea, and hematochezia, which can even cause death. Although the current preferred regimen for the treatment of coccidiosis is antibiotics, this treatment strategy is limited by the ban on antibiotics and the growing problem of drug resistance. Therefore, the exploration of alternative methods for controlling coccidiosis has attracted much attention. Lactobacillus plantarum has been shown to have many beneficial effects. In this study, L. plantarum M2 was used as a research object to investigate the effect of L. plantarum on intestinal inflammation induced by infection with Eimeria falciformis in mice by detecting indicators, such as oocyst output, serum cytokines, and the intestinal microbiota. Compared with that in the infection group, the percent weight loss of the mice that were administered with L. plantarum M2 was significantly reduced (P < 0.05). Supplemented L. plantarum M2 and probiotics combined with diclazuril can reduce the total oocyst output significantly (P < 0.05, P < 0.001). L. plantarum M2 had outstanding performance in maintaining intestinal barrier function, and the levels of the mucin MUC1 and the tight junction protein E-cadherin were significantly elevated (P < 0.01, P < 0.05). Studies have shown that probiotic supplementation can alleviate adverse reactions after infection and significantly improve intestinal barrier function. In addition, probiotics combined with diclazuril could optimize the partial efficacy of diclazuril, which not only enhanced the effect of antibiotics but also alleviated their adverse effects. This study expands the application of probiotics, provides new ideas for alternative strategies for coccidia control, and suggests a basis for related research on lactobacilli antagonizing intracellular pathogen infection.IMPORTANCECoccidia of the genus Eimeria are specialized intracellular parasitic protozoa, and the current preferred regimen for the treatment of coccidiosis is antibiotics. However, due to antibiotic bans and drug resistance, the exploration of alternative methods for controlling coccidiosis has attracted much attention. In this work, we focused on Lactobacillus plantarum M2 and found that probiotic supplementation can alleviate adverse reactions after infection and improve intestinal barrier function. This study proposes the possibility of using lactic acid bacteria to control coccidiosis, and its potential mechanism needs further exploration.

Unveiling the Brazilian kefir microbiome: discovery of a novel Lactobacillus kefiranofaciens (LkefirU) genome and in silico prospection of bioactive peptides with potential anti-Alzheimer properties.

BACKGROUND: Kefir is a complex microbial community that plays a critical role in the fermentation and production of bioactive peptides, and has health-improving properties. The composition of kefir can vary by geographic localization and weather, and this paper focuses on a Brazilian sample and continues previous work that has successful anti-Alzheimer properties. In this study, we employed shotgun metagenomics and peptidomics approaches to characterize Brazilian kefir further. RESULTS: We successfully assembled the novel genome of Lactobacillus kefiranofaciens (LkefirU) and conducted a comprehensive pangenome analysis to compare it with other strains. Furthermore, we performed a peptidome analysis, revealing the presence of bioactive peptides encrypted by L. kefiranofaciens in the Brazilian kefir sample, and utilized in silico prospecting and molecular docking techniques to identify potential anti-Alzheimer peptides, targeting ß-amyloid (fibril and plaque), BACE, and acetylcholinesterase. Through this analysis, we identified two peptides that show promise as compounds with anti-Alzheimer properties. CONCLUSIONS: These findings not only provide insights into the genome of L. kefiranofaciens but also serve as a promising prototype for the development of novel anti-Alzheimer compounds derived from Brazilian kefir.

Metabolomic and Transcriptomic Correlative Analyses in Germ-Free Mice Link Lacticaseibacillus rhamnosus GG-Associated Metabolites to Host Intestinal Fatty Acid Metabolism and ß-Oxidation.

Intestinal microbiota confers susceptibility to diet-induced obesity, yet many probiotic species that synthesize tryptophan (trp) actually attenuate this effect, although the underlying mechanisms are unclear. We monocolonized germ-free mice with a widely consumed probiotic Lacticaseibacillus rhamnosus GG (LGG) under trp-free or -sufficient dietary conditions. We obtained untargeted metabolomics from the mouse feces and serum using liquid chromatography-mass spectrometry and obtained intestinal transcriptomic profiles via bulk-RNA sequencing. When comparing LGG-monocolonized mice with germ-free mice, we found a synergy between LGG and dietary trp in markedly promoting the transcriptome of fatty acid metabolism and ß-oxidation. Upregulation was specific and was not observed in transcriptomes of trp-fed conventional mice and mice monocolonized with Ruminococcus gnavus. Metabolomics showed that fecal and serum metabolites were also modified by LGG-host-trp interaction. We developed an R-Script-based MEtabolome-TRanscriptome Correlation Analysis algorithm and uncovered LGG- and trp-dependent metabolites that were positively or negatively correlated with fatty acid metabolism and ß-oxidation gene networks. This high-throughput metabolome-transcriptome correlation strategy can be used in similar investigations to reveal potential interactions between specific metabolites and functional or disease-related transcriptomic networks.

The Oral Administration of Lactobacillus delbrueckii subsp. lactis 557 (LDL557) Ameliorates the Progression of Monosodium Iodoacetate-Induced Osteoarthritis.

Low-grade body inflammation is a major cause of osteoarthritis (OA), a common joint disease. Gut dysbiosis may lead to systemic inflammation which can be prevented by probiotic administration. The Lactobacillus delbrueckii subsp. lactis 557 (LDL557) has been demonstrated to have beneficial effects for anti-inflammation. This study investigated the effects of LDL557 on OA progress using monosodium iodoacetate (MIA)-induced OA of rats. Live or heat-killed (HK)-LDL557 of a low or high dose was administrated for two weeks before MIA-induced OA, and then continuously administrated for another six weeks. After taking supplements for eight weeks, OA progress was analyzed. Results showed that MIA induced knee joint swelling, chondrocyte damage, and cartilage degradation, and supplementation with a high dose of LDL557 reduced MIA-induced knee joint swelling, chondrocyte damage, and cartilage degradation. Additionally, MIA increased serum levels of the matrix-degrading enzyme MMP-13, while a high dose of HK-LDL557 decreased it for the controls. Simultaneously, bone turnover markers and inflammatory cytokines of serum were assayed, but no significant differences were found except for a TNF-α decrease from a low dose of live LDL557. These results demonstrated that supplementation with high doses of live LDL557 or HK-LDL557 can reduce the progression of MIA-induced OA in rats.

Suppression of UVB-Induced MMP-1 Expression in Human Skin Fibroblasts Using Lysate of Lactobacillus iners Derived from Korean Women's Skin in Their Twenties.

The process of skin aging is intricate, involving intrinsic aging, influenced by internal factors, and extrinsic aging, mainly caused by exposure to UV radiation, resulting in photoaging. Photoaging manifests as skin issues such as wrinkles and discoloration. The skin microbiome, a diverse community of microorganisms on the skin's surface, plays a crucial role in skin protection and can be affected by factors like humidity and pH. Probiotics, beneficial microorganisms, have been investigated for their potential to enhance skin health by regulating the skin microbiome. This can be accomplished through oral probiotics, impacting the gut-skin axis, or topical applications introducing live bacteria to the skin. Probiotics mitigate oxidative stress, suppress inflammation, and maintain the skin's extracellular matrix, ultimately averting skin aging. However, research on probiotics derived from human skin is limited, and there is no established product for preventing photoaging. The mechanism by which probiotics shield the skin microbiome and skin layers from UV radiation remains unclear. Recently, researchers have discovered Lactobacillus in the skin, with reports indicating a decrease in this microorganism with age. In a recent study, scientists isolated Lactobacillus iners KOLBM20 from the skin of individuals in their twenties and confirmed its effectiveness. A comparative analysis of genetic sequences revealed that strain KOLBM20 belongs to the Lactobacillus genus and closely relates to L. iners DSM13335(T) with a 99.20% similarity. Importantly, Lactobacillus iners KOLBM20 displayed anti-wrinkle properties by inhibiting MMP-1. This investigation demonstrated the inhibitory effect of KOLBM20 strain lysate on MMP-1 expression. Moreover, the data suggest that KOLBM20 strain lysate may prevent UVB-induced MMP-1 expression by inhibiting the activation of the ERK, JNK, and p38 signaling pathways induced by UVB. Consequently, KOLBM20 strain lysate holds promise as a potential therapeutic agent for preventing and treating skin photoaging.