Anti-tuberculosis effect of microbiome therapeutic PMC205 in extensively drug-resistant pulmonary tuberculosis in vivo.

BACKGROUND: Tuberculosis is a highly contagious disease caused by Mycobacterium tuberculosis, and the increase in antibiotic resistance threatens humankind. Therefore, there is an urgent need to develop new anti-tuberculosis drugs that can overcome the limitations of existing drugs. Here, we report the anti-tuberculosis effect of microbiome therapeutic PMC205, a strain of Bacillus subtilis. METHODS: The anti-tuberculosis activity of probiotics was evaluated in mouse models of lethal and latent pulmonary tuberculosis induced by high or low-dose infection of the extensively drug-resistant (XDR) strain. Probiotics were administered by inhalation, and the burden of M. tuberculosis in the lungs, along with mortality and clinical observations, were monitored for 12 weeks and 8 months, respectively. For an in-depth understanding, analysis of the microbiome and inflammatory profile of the lung microenvironment and induction of autophagy in vitro were explored. RESULTS: After inhalation administration of PMC205 for 3 months, the survival rate was 100%, unlike all deaths in the saline-treated group, and the burden of M. tuberculosis in the lungs was reduced by log 1.3 in the 8-month latent tuberculosis model. Moreover, PMC205 induced recovery of disrupted lung microflora, increased butyric acid, and suppressed excessive inflammation. It also promoted autophagy. CONCLUSIONS: These results confirm PMC205's anti-tuberculosis effect, suggesting that it can be developed as an adjuvant to current antibiotic therapy to solve the drug-resistant tuberculosis problem.

Exploring the potential of Lactocaseibacillus rhamnosus PMC203 in inducing autophagy to reduce the burden of Mycobacterium tuberculosis.

Mycobacterium tuberculosis, a lethal pathogen in human history, causes millions of deaths annually, which demands the development of new concepts of drugs. Considering this fact, earlier research has explored the anti-tuberculosis potential of a probiotic strain, Lactocaseibacillus rhamnosus PMC203, leading to a subsequent focus on the molecular mechanism involved in its effect, particularly on autophagy. In this current study, immunoblotting-based assay exhibited a remarkable expression of autophagy marker LC3-II in the PMC203 treated group compared to an untreated group. A remarkable degradation of p62 was also noticed within treated cells compared to control. Furthermore, the immunofluorescence-based assay showed significant fold change in fluorescence intensity for alexa-647-LC3 and alexa-488-LC3, whereas p62 was degraded noticeably. Moreover, lysosomal biogenesis generation was elevated significantly in terms of LAMP1 and acidic vesicular organelles. As a result, PMC203-induced autophagy played a vital role in reducing M. tuberculosis burden within the macrophages in treated groups compared to untreated group. A colony -forming unit assay also revealed a significant reduction in M. tuberculosis in the treated cells over time. Additionally, the candidate strain significantly upregulated the expression of autophagy induction and lysosomal biogenesis genes. Together, these results could enrich our current knowledge of probiotics-mediated autophagy in tuberculosis and suggest its implications for innovatively managing tuberculosis.

Clinical effect of Pediococcus acidilactici PMC48 on hyperpigmented skin.

BACKGROUND: The excessive production and accumulation of melanin in the epidermal skin layer can result in skin hyperpigmentation and darkening. Current technologies for regulating melanin are based on inhibiting melanin biosynthesis. They have low effectiveness and safety issues. AIMS: This study aimed to evaluate the potential role of Pediococcus acidilactici PMC48 as a probiotic strain in medicines and cosmetics for skin treatment. MATERIALS AND METHODS: Meanwhile, our research team has reported that P. acidilactici PMC48 strain isolated from sesame leaf kimchi can directly decompose the already synthesized melanin. It can also inhibit melanin biosynthesis. In the present study, we investigated the skin-whitening effect of this strain by arranging an 8-week clinical trial with 22 participants. PMC48 was applied to each participant's artificially UV-induced tanned skin in the clinical trial. Its whitening effect was investigated based on visual evaluation, skin brightness, and melanin index. RESULTS: PMC48 showed a significant effect on the artificially induced pigmented skin. The color intensity of the tanned skin was decreased by 47.647%, and skin brightness was increased by 8.098% after the treatment period. PMC48 also significantly decreased the melanin index by 11.818%, indicating its tyrosinase inhibition capacity. Also, PMC48 improved skin moisture content level by 20.943%. Additionally, 16S rRNA-based amplicon sequencing analysis showed a distinct increase in Lactobacillaceae in the skin by up to 11.2% at the family level without affecting other skin microbiota. Furthermore, it showed no toxicity in in vitro or in vivo analyses. DISCUSSION: These results indicate that P. acidilactici PMC48 is a promising probiotic strain that can be used to develop medicines and cosmetic products to solve skin-related problems. CONCLUSIONS: These results demonstrate that P. acidilactici PMC48 can be a potential probiotic for the cosmetic industry against different skin disorders.

The Effects of Iron Deficiency on the Gut Microbiota in Women of Childbearing Age.

Iron deficiency anemia (IDA) is the most prevalent and common nutritional deficiency worldwide and is a global health problem with significant risk, particularly among women of reproductive age. Oral iron supplementation is the most widely used and cost-effective treatment for iron deficiency and IDA. However, there are limitations regarding side effects such as enteritis, treatment compliance, and bioavailability. Intestinal microbiome characteristic research has been recently conducted to overcome these issues, but more is needed. Against this background, a metagenomics study on the 16S gene in the feces of young women vulnerable to IDA was conducted. As a result of analyzing 16 normal subjects and 15 IDA patients, significant differences in bacterial community distribution were identified. In particular, a significant decrease in Faecalibacterium was characteristic in IDA patients compared with normal subjects. Furthermore, in the case of patients who recovered from IDA following iron supplementation treatment, it was confirmed that Faecalibacterium significantly recovered to normal levels. However, no significance in beta diversity was seen compared with before treatment. There were also no differences in the beta diversity results between the recovered and normal subjects. Therefore, intestinal dysbiosis during the disease state was considered to be restored as IDA improved. Although the results were derived from a limited number of subjects and additional research is needed, the results of this study are expected to be the basis for developing treatment and prevention strategies based on host-microbiome crosstalk in IDA.

In Vivo Efficacy of Bacillus velezensis Isolated from Korean Gochang Bokbunja Vinegar against Carbapenem-Resistant Klebsiella pneumoniae Infections.

Outbreaks of carbapenem-resistant Enterobacteriaceae (CRE), especially Klebsiella pneumoniae (CRKP), are commonly reported as severe infections in hospitals and long-term care settings, and their occurrence is increasing globally. Conventional antibiotics used for treating CRE have become ineffective due to resistance development. Furthermore, their safety issues restrict their availability and use for CRE treatment. Therefore, developing new drugs different from existing drugs to combat this deadly menace is urgently needed. Probiotics can be a potential option in this context, as probiotics' efficacy against a variety of infectious illnesses has already been well established. Here, we report the effect of the Bacillus velezensis strain isolated from Gochang Bokbunja vinegar in Korea on CRE infection using two mouse models. Data showed that pretreatment with B. velezensis significantly reduced body weight loss and mortality of CRKP-infected mice in the preventive model. The oral administration of B. velezensis in a therapeutic model also decreased the mortality and illness severity in CRKP-infected mice. Moreover, a two-week oral acute toxicity assay in guinea pigs did not reveal any aberrant clinical signs. Our findings demonstrate the potential effectiveness of our candidate probiotic strain, B. velezensis, against CRKP, suggesting that it could be used as an antimicrobial agent for treating CRKP-related infections.