Heat-killed Akkermansia muciniphila ameliorates allergic airway inflammation in mice.

Allergic asthma (AA) is a common inflammatory airway disease characterized by increased airway hyper-responsiveness (AHR), inflammation, and remodeling. Akkermansia muciniphila is a strictly anaerobic bacterium residing in the gut and is a promising next-generation probiotic to improve metabolic inflammatory syndrome. A recent study suggested the beneficial effect of live A. muciniphila on allergic airway inflammation (AAI) in mice. However, whether the heat-killed form can improve AAI requires further investigation. Mice sensitized and challenged with house dust mites (HDM) develop AA hallmarks including inflammatory cell infiltration, goblet cell hyperplasia, and subepithelial collagen deposition in the lungs. These phenomena were reversed by oral administration of the heat-killed A. muciniphila strain EB-AMDK19 (AMDK19-HK) isolated from the feces of healthy Koreans. Furthermore, AMDK19-HK diminished the HDM-induced AHR to inhaled methacholine, lung mast cell accumulation, and serum HDM-specific IgE levels. It also led to the overall suppression of IL-4, IL-13, and eotaxin production in bronchoalveolar lavage fluids, and Il4, Il5, Il13, and Ccl17 gene expression in lung tissues. Moreover, AMDK19-HK suppressed Th2-associated cytokine production in the splenocytes of HDM-sensitized mice in vitro. Additionally, a combination of 16S rRNA gene sequencing and short-chain fatty acid (SCFA) analysis in cecal samples revealed that AMDK19-HK modulated the relative abundance of circulating SCFA-associated gut genera, including a positive correlation with Lachnospiraceae_ NK4A136_group and a negative correlation with Lachnoclostridium and significantly increased cecal SCFA concentrations. Finally, AMDK19-HK improved intestinal mucosal barrier function. These results suggest that the oral administration of AMDK19-HK ameliorates HDM-induced AAI in mice by suppressing Th2-mediated immune responses and could have a protective effect against AA development.

Akkermansia muciniphila promotes testosterone-mediated hair growth inhibition in mice.

The beneficial effects of Akkermansia muciniphila (Akk) on gut health and inflammation reduction have been demonstrated; however, scientific evidence of hair growth enhancement by Akk has not been reported. Therefore, this study was undertaken to investigate the effect of Akk on improving testosterone-mediated hair growth inhibition. Hair growth inhibition was induced through subcutaneous injection of testosterone into the shaved dorsal skin of C57BL/6 male mice. Live and pasteurized Akk were orally administered at a concentration of 1 × 108 colony-forming unit. After 5 weeks, hair length and skin tissues were analyzed. The live and pasteurized Akk significantly stimulated hair growth, countering the inhibitory effect of testosterone compared to the testosterone-alone group. Hematoxylin and eosin staining revealed a significant increase in hair follicle size in the Akk-treated group. An increase in ß-catenin levels, which are associated with hair growth and cell cycle progression, was also observed. Moreover, the Akk-treated group exhibited increased levels of fibroblast growth factors, including Fgf7, Igf1, Fgf7, Fgf10, and Fgf21. However, no significant difference was observed between the live and pasteurized Akk groups. These results underscore the potential of live and pasteurized Akk in improving testosterone-mediated hair growth inhibition.

New Strains of Akkermansia muciniphila and Faecalibacterium prausnitzii are Effective for Improving the Muscle Strength of Mice with Immobilization-Induced Muscular Atrophy.

Muscular atrophy is a muscle disease in which muscle mass and strength decrease due to aging, injury, metabolic disorders, or chronic conditions. Proteins in muscle tissue are degraded by the ubiquitin-proteasome pathway, and atrophy accelerates this pathway. Akkermansia muciniphila and Faecalibacterium prausnitzii strains are effective agents against metabolic and inflammatory diseases in next-generation probiotic research. In this study, we evaluated the efficacy of A. muciniphila strain EB-AMDK19 and F. prausnitzii strain EB-FPDK11 in a mouse model of muscular atrophy, since atrophy inhibits energy metabolism and immune activation. After oral administration of each strain for 4 weeks, the hind legs of the mice were fixed with a plaster cast to immobilize them for a week. As a result, the administration of EB-AMDK19 and EB-FPDK11 strains improved grip strength but did not increase muscle mass. At the molecular level, A. muciniphila and F. prausnitzii treatments decreased the expression levels of ubiquitin-proteasome genes, atrogin-1, MuRF, and cathepsin L. They increased the expression level of the mitochondrial biogenesis regulatory gene, PGC-1α. The effect of the strains was confirmed by a decrease in myostatin. Furthermore, A. muciniphila and F. prausnitzii modulated the immune function by enhancing ZO-1 and inhibiting IL-6. In particular, EB-AMDK19 promoted the expression of IL-10, an anti-inflammatory cytokine. These results suggest that A. muciniphila and F. prausnitzii may have beneficial effects on muscular atrophy, verified by newly isolated EB-AMDK19 and EB-FPDK11 as potential next-generation probiotics.

Oral administration of Faecalibacterium prausnitzii and Akkermansia muciniphila strains from humans improves atopic dermatitis symptoms in DNCB induced NC/Nga mice.

Atopic dermatitis (AD) is a common inflammatory skin disease, and its pathogenesis is closely associated with microbial homeostasis in the gut, namely the gut-skin axis. Particularly, recent metagenomics studies revealed that the abundance of two major bacterial species in the gut, Faecalibacterium prausnitzii and Akkermansia muciniphila, may play a critical role in the pathogenesis of AD, but the effect of these species in AD has not yet been elucidated. To evaluate the potential beneficial effect of F. prausnitzii or A. muciniphila in AD, we conducted an animal model study where F. prausnitzii EB-FPDK11 or A. muciniphila EB-AMDK19, isolated from humans, was orally administered to 2,5-dinitrochlorobenzene (DNCB)-induced AD models using NC/Nga mice at a daily dose of 108 CFUs/mouse for six weeks. As a result, the administration of each strain of F. prausnitzii and A. muciniphila improved AD-related markers, such as dermatitis score, scratching behavior, and serum immunoglobulin E level. Also, the F. prausnitzii and A. muciniphila treatments decreased the level of thymic stromal lymphopoietin (TSLP), triggering the production of T helper (Th) 2 cytokines, and improved the imbalance between the Th1 and Th2 immune responses induced by DNCB. Meanwhile, the oral administration of the bacteria enhanced the production of filaggrin in the skin and ZO-1 in the gut barrier, leading to the recovery of functions. Taken together, our findings suggest that F. prausnitzii EB-FPDK11 and A. muciniphila EB-AMDK19 have a therapeutic potential in AD, which should be verified in humans.

Chthonobacter albigriseus gen. nov., sp. nov., isolated from grass-field soil.

A novel aerobic, Gram-stain-negative and non-motile bacterial strain, designated ED7T, was isolated from grass-field soil in Cheonan, Korea. Strain ED7T utilized methanol and methylamine, but not formate, as carbon and energy sources. The strain was able to grow at 20-42 °C (optimum 30-35 °C), at pH 7.0-8.5 (optimum pH 7.5-8.0), and in the absence of NaCl. According to the similarities of the 16S rRNA gene sequences, strain ED7T was most closely related to the genera Labrenzia (≤93.3 % 16S rRNA gene sequence similarity), Pleomorphomonas (≤93.1 %) and Prosthecomicrobium (≤93.1 %). A phylogenetic analysis based on the 16S rRNA gene sequence of strain ED7T revealed that it was affiliated with the family Methylocystaceae, being most closely related to the genus Pleomorphomonas. In contrast to Pleomorphomonas koreensis and Pleomorphomonas oryzae, strain ED7T did not contain the nifH gene. The DNA G+C content of the genomic DNA of strain ED7T was 71.8 mol%. The predominant fatty acids of strain ED7T were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), summed feature 2 (C14 : 0 3-OH, and/or C16 : 1 iso I), 11-methyl C18 : 1ω7c and C16 : 0 3-OH. The major isoprenoid quinone was ubiquinone 10 (Q-10). The major polar lipids were phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine and an unknown aminophospholipid. Based on phenotypic, chemotaxonomic and genotypic characteristic data, strain ED7T could be differentiated from other genera, suggesting that strain ED7T represents a novel species of a new genus in the family Methylocystaceae, for which the name Chthonobacter albigriseus gen. nov., sp. nov. is proposed. The type strain of the type species is ED7T (=JCM 30603T=KCTC 42450T).

Flavobacterium eburneum sp. nov., isolated from reclaimed saline land soil.

A novel Gram-stain-negative, motile by gliding, and aerobic bacterial strain, designated SA31T, was isolated from reclaimed saline land soil near a lake in Taean-gun, South Korea. Cells of the isolate formed ivory-coloured colonies. Growth occurred at 10-35 °C (optimum 25-30 °C), pH 6.0-9.0 (optimum pH 7.0-7.5), and 0-2.0 % (w/v) NaCl (optimum 0 %). Based on similarities of 16S rRNA gene sequences, strain SA31T was mostly affiliated with the genus Flavobacterium, exhibiting the highest sequence similarities with Flavobacterium palustre S44T (96.0 %), Flavobacterium glycines Gm-149T (95.9 %), Flavobacterium defluvii EMB117T (95.7 %) and Flavobacterium daejeonense GH1-10T (95.6 %). Phylogenetic analysis based on 16S rRNA gene sequences also indicated that strain SA31T was clustered with Flavobacterium daejeonense GH1-10T and Flavobacterium glycines Gm-149T. The predominant fatty acids (>7 % of total) of strain SA31T were iso-C15 : 0, summed feature 3 (C16 : 1ω7с and/or C16 : 1ω6с), iso-C17 : 0 3-OH and iso-C15 : 0 3-OH. The major polar lipids of the isolate comprised phosphatidylethanolamine, one unknown aminolipid, one unknown glycolipid, one unknown aminophospholipid and three unknown lipids. The major respiratory quinone was MK-6. The genomic DNA G+C content of strain SA31T was 33.5 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic analyses, strain SA31T represents a novel species the genus Flavobacterium, for which the name Flavobacterium eburneum sp. nov. is proposed. The type strain is SA31T (=KACC 18743T=JCM 31221T).

Dankookia rubra gen. nov., sp. nov., an alphaproteobacterium isolated from sediment of a shallow stream.

WS-10(T)-a Gram-negative, non-motile, and aerobic bacterial strain-was isolated from the sediment of a shallow stream in Korea. The optimum ranges of temperature and pH for growth were 20-40°C (optimum 28°C) and pH 6.0-8.0 (optimum pH 7.0), respectively. The DNA G+C content of strain WS-10(T) was 72.7 mol%. The major fatty acids (>5%) were summed feature 8 (C18:1 ω7c), summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C16:0, and C18:1 2-OH. The major polar lipids consisted of phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, and unidentified aminolipids. Q-10 was the predominant respiratory quinone. The highest similarities in the 16S rRNA gene sequence were shown with Paracraurococcus ruber (95.3%), Belnapia soli (95.3%), B. moabensis (95.1%), and B. rosea (95.0%). A phylogenetic analysis based on 16S rRNA gene sequence comparisons showed that strain WS-10T formed a distinct line within a clade containing the genera Paracraurococcus, Craurococcus, and Belnapia in the family Acetobacteraceae. On the basis of polyphasic evidence, strain WS-10(T) represents a novel species of a new genus in the family Acetobacteraceae, for which the name Dankookia rubra gen. nov., sp. nov. is proposed. The type strain of the type species is WS-10(T) (= KACC 18533(T) = JCM 30602(T)).