Immunobiotic Bacteria Attenuate Hepatic Fibrosis through the Modulation of Gut Microbiota and the Activation of Aryl-Hydrocarbon Receptors Pathway in Non-Alcoholic Steatohepatitis Mice.

SCOPE: Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease worldwide that can progress to liver fibrosis (LF). Probiotics have beneficial roles in reducing intestinal inflammation and gut-associated diseases, but their effects and mechanisms beyond the gut in attenuating the progression of LF are remained unclear. METHODS AND RESULTS: In a mouse model of NASH/LF induced by a methionine-choline deficient (MCD) diet, immunobiotics are administered to investigate their therapeutic effects. Results show that the MCD diet leads to liver inflammation, steatosis, and fibrosis, which are alleviated by immunobiotics. Immunobiotics reduces serum endotoxin and inflammatory markers while increasing regulatory cytokines and liver weight. They also suppress Th17 cells, known for producing inflammatory cytokines. Furthermore, immunobiotics mitigate collagen deposition and fibrogenic signaling in the liver, while restoring gut-barrier integrity and microbiota composition. Additionally, immunobiotics enhance the activation of the aryl hydrocarbon receptor (AhR) pathway in both colonic and liver tissues. CONCLUSIONS: Overall, these results demonstrate a novel insight into the mechanisms through which immunobiotic administration improves the gut health which in turn increases the AhR pathway and inhibits HSCs activation and fibrosis progression beyond the gut in the liver tissue of NASH/LF mice.

Lacticaseibacillus paracasei completely utilizes fructooligosacchrides in the human gut through ß-fructosidase (FosE).

The fecal microbiota of two healthy adults was cultivated in a medium containing commercial fructooligosaccharides [FOS; 1-kestose (GF2), nystose (GF3), and 1F-fructofuranosylnystose (GF4)]. Initially, the proportions of lactobacilli in the two feces samples were only 0.42% and 0.17%; however, they significantly increased to 7.2% and 4.8%, respectively, after cultivation on FOS. Most FOS-utilizing isolates could utilize only GF2; however, Lacticaseibacillus paracasei strain Lp02 could fully consume GF3 and GF4 too. The FOS operon (fosRABCDXE) was present in Lc. paracasei Lp02 and another Lc. paracasei strain, KCTC 3510T, but fosE was only partially present in the non-FOS-degrading strain KCTC 3510T. In addition, the top six upregulated genes in the presence of FOS were fosABCDXE, particularly fosE. FosE is a ß-fructosidase that hydrolyzes both sucrose and all three FOS. Finally, a genome-based analysis suggested that fosE is mainly observed in Lc. paracasei, and only 13.5% (61/452) of their reported genomes were confirmed to include it. In conclusion, FosE allows the utilization of FOS, including GF3 and GF4 as well as GF2, by some Lc. paracasei strains, suggesting that this species plays a pivotal role in FOS utilization in the human gut.

Fecal Microbial Dysbiosis is Associated with Colorectal Cancer Risk in a Korean Population.

Purpose: The association between the fecal microbiota and colorectal cancer (CRC) risk has been suggested in epidemiologic studies. However, data from large-scale population-based studies are lacking. Materials and Methods: In this case-control study, we recruited 283 CRC patients from the Center for Colorectal Cancer, National Cancer Center Hospital, Korea to perform 16S rRNA gene sequencing of fecal samples. A total of 283 age- and sex-matched healthy participants were selected from 890 cohort of healthy Koreans that are publicly available (PRJEB33905). The microbial dysbiosis index (MDI) was calculated based on the differentially abundant species. The association between MDI and CRC risk was observed using conditional logistic regression. Sparse Canonical Correlation Analysis was performed to integrate species data with microbial pathways obtained by PICRUSt2. Results: There is a significant divergence of the microbial composition between CRC patients and controls (PERMANOVA p=0.001). Those who were in third tertile of the MDI showed a significantly increased risk of CRC in the total population (OR: 6.93, 95% CI: 3.98-12.06, p-trend<0.001) compared to those in the lowest tertile. Similar results were found for men (OR: 6.28, 95% CI: 3.04-12.98-, p-trend<0.001) and women (OR: 7.39, 95% CI: 3.10-17.63, p-trend<0.001). Bacteroides coprocola and Bacteroides plebeius species and 12 metabolic pathways were interrelated in healthy controls that explain 91% covariation across samples. Conclusion: Dysbiosis in the fecal microbiota may be associated with an increased risk of CRC. Due to the potentially modifiable nature of the gut microbiota, our findings may have implications for CRC prevention among Koreans.

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.

Ginseng extracts improve circadian clock gene expression and reduce inflammation directly and indirectly through gut microbiota and PI3K signaling pathway.

Despite the potential benefits of herbal medicines for therapeutic application in preventing and treating various metabolic disorders, the mechanisms of action were understood incompletely. Ginseng (Panax ginseng), a commonly employed plant as a dietary supplement, has been reported to play its hot property in increasing body temperature and improving gut health. However, a comprehensive understanding of the mechanisms by which ginseng regulates body temperature and gut health is still incomplete. This paper illustrates that intermittent supplementation with ginseng extracts improved body temperature rhythm and suppressed inflammatory responses in peripheral metabolic organs of propylthiouracil (PTU)-induced hypothermic rats. These effects were associated with changes in gut hormone secretion and the microbiota profile. The in-vitro studies in ICE-6 cells indicate that ginseng extracts can not only act directly on the cell to regulate the genes related to circadian clock and inflammation, but also may function through the gut microbiota and their byproducts such as lipopolysaccharide. Furthermore, administration of PI3K inhibitor blocked ginseng or microbiota-induced gene expression related with circadian clock and inflammation in vitro. These findings demonstrate that the hot property of ginseng may be mediated by improving circadian clock and suppressing inflammation directly or indirectly through the gut microbiota and PI3K-AKT signaling pathways.

Associations among the Duodenal Ecosystem, Gut Microbiota, and Nutrient Intake in Functional Dyspepsia.

Background/Aims: : Functional dyspepsia (FD) has long been regarded as a syndrome because its pathophysiology is multifactorial. However, recent reports have provided evidence that changes in the duodenal ecosystem may be the key. This study aimed to identify several gastrointestinal factors and biomarkers associated with FD, specifically changes in the duodenal ecosystem that may be key to understanding its pathophysiology. Methods: : In this case-control study, 28 participants (12 with FD and 16 healthy control individuals) were assessed for dietary nutrients, gastrointestinal symptom severity, immunological status of the duodenal mucosa, and microbiome composition from oral, duodenal, and fecal samples. Integrated data were analyzed using immunohistochemistry, real-time polymerase chain reaction, 16S rRNA sequencing, and network analysis. Results: : Duodenal mucosal inflammation and impaired expression of tight junction proteins were confirmed in patients with FD. The relative abundance of duodenal Streptococcus (p=0.014) and reductions in stool Butyricicoccus (p=0.047) were confirmed. These changes in the gut microbiota were both correlated with symptom severity. Changes in dietary micronutrients, such as higher intake of valine, were associated with improved intestinal barrier function and microbiota. Conclusions: : This study emphasizes the relationships among dietary nutrition, oral and gut microbiota, symptoms of FD, impaired function of the duodenal barrier, and inflammation. Assessing low-grade inflammation or increased permeability in the duodenal mucosa, along with changes in the abundance of stool Butyricicoccus, is anticipated to serve as effective biomarkers for enhancing the objectivity of FD diagnosis and monitoring.

A Novel Carotenoid-Producing Bacterium, Paenibacillus aurantius sp. nov., Isolated from Korean Marine Environment.

The novel bacterial strain MBLB1776T was isolated from marine mud in Uljin, the Republic of Korea. Cells were Gram-positive, spore-forming, non-motile, and non-flagellated rods. Growth was observed at a temperature range of 10-45 °C, pH range of 6.0-8.0, and NaCl concentrations of 0-4% (w/v). Phylogenetic analysis of the 16S rRNA gene sequence revealed that MBLB1776T belonged to the genus Paenibacillus and was closely related to Paenibacillus cavernae C4-5T (94.83% similarity). Anteiso-C15:0, iso-C16:0, C16:0, and iso-C15:0 were the predominant fatty acids. Menaquinone 7 was identified as the major isoprenoid quinone. The major polar lipids included diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine. Its whole genome was 6.3 Mb in size, with a G+C content of 55.8 mol%. Average nucleotide identity and in silico DNA-DNA hybridization values were below the species delineation threshold. Gene function analysis revealed the presence of a complete C30 carotenoid biosynthetic pathway. Intriguingly, MBLB1776T harbored carotenoid pigments, imparting an orange color to whole cells. Based on this comprehensive polyphasic taxonomy, the MBLB1776T strain represents a novel species within the genus Paenibacillus, for which the name Paenibacillus aurantius sp. nov is proposed. The type strain was MBLB1776T (=KCTC 43279T = JCM 34220T). This is the first report of a carotenoid-producing Paenibacillus sp.

Gut microbiome in healthy aging versus those associated with frailty.

As the proportion of older people in the world's population steadily increases, there is an urgent need to identify ways to support healthy aging. The gut microbiome has been proposed to be involved in aging-related diseases and has become an attractive target for improving health in older people. Herein, we cover the relationship between the gut microbiome and chronological age in adults, and then, we discuss the gut microbiome features associated with frailty, as a hallmark of unhealthy aging in older people. Furthermore, we describe the effects of microbiome-targeted interventions, such as dietary patterns and consumption of probiotics, prebiotics, and synbiotics, on modulating the gut microbiome composition and further promoting healthy aging. Further studies are needed to explore the underlying mechanisms of gut microbiome-induced aging complications and to develop personalized microbiome-based strategies for reducing the severity of frailty or preventing the onset of frailty in older adults.

Prior antibiotic administration disrupts anti-PD-1 responses in advanced gastric cancer by altering the gut microbiome and systemic immune response.

Evidence on whether prior antibiotic (pATB) administration modulates outcomes of programmed cell death protein-1 (PD-1) inhibitors in advanced gastric cancer (AGC) is scarce. In this study, we find that pATB administration is consistently associated with poor progression-free survival (PFS) and overall survival (OS) in multiple cohorts consisting of patients with AGC treated with PD-1 inhibitors. In contrast, pATB does not affect outcomes among patients treated with irinotecan. Multivariable analysis of the overall patients treated with PD-1 inhibitors confirms that pATB administration independently predicts worse PFS and OS. Administration of pATBs is associated with diminished gut microbiome diversity, reduced abundance of Lactobacillus gasseri, and disproportional enrichment of circulating exhaustive CD8+ T cells, all of which are associated with worse outcomes. Considering the inferior treatment response and poor survival outcomes by pATB administration followed by PD-1 blockade, ATBs should be prescribed with caution in patients with AGC who are planning to receive PD-1 inhibitors.

Pharmaceutical efficacy of novel human-origin Faecalibacterium prausnitzii strains on high-fat-diet-induced obesity and associated metabolic disorders in mice.

Introduction: Obesity and related metabolic issues are a growing global health concern. Recently, the discovery of new probiotics with anti-obesity properties has gained interest. Methods: In this study, four Faecalibacte-rium prausnitzii strains were isolated from healthy human feces and evaluated on a high-fat diet-induced mouse model for 12 weeks. Results: The F. prausnitzii strains reduced body weight gain, liver and fat weights, and calorie intake while improving lipid and glucose metabolism in the liver and adipose tissue, as evidenced by regulating lipid metabolism-associated gene expression, including ACC1, FAS, SREBP1c, leptin, and adiponectin. Moreover, the F. prausnitzii strains inhibited low-grade inflammation, restored gut integrity, and ameliorated hepatic function and insulin resistance. Interestingly, the F. prausnitzii strains modulated gut and neural hormone secretion and reduced appetite by affecting the gut-brain axis. Supplementation with F. prausnitzii strains noticeably changed the gut microbiota composition. Discussion: In summary, the novel isolated F. prausnitzii strains have therapeutic effects on obesity and associated metabolic disorders through modulation of the gut-brain axis. Additionally, the effectiveness of different strains might not be achieved through identical mechanisms. Therefore, the present findings provide a reliable clue for developing novel therapeutic probiotics against obesity and associated metabolic disorders.

Gut microbial change after administration of Lacticaseibacillus paracasei AO356 is associated with anti-obesity in a mouse model.

Introduction: The status of an impaired gut microbial community, known as dysbiosis, is associated with metabolic diseases such as obesity and insulin resistance. The use of probiotics has been considered an effective approach for the treatment and prevention of obesity and related gut microbial dysbiosis. The anti-obesity effect of Lacticaseibacillus paracasei AO356 was recently reported. However, the effect of L. paracasei AO356 on the gut microbiota has not yet been identified. This study aimed to elucidate the effect of L. paracasei AO356 on gut microbiota and ensure its safety for use as a probiotic. Methods: Oral administration of L. paracasei AO356 (107 colony-forming units [CFU]/mg per day, 5 days a week, for 10 weeks) to mice fed a high-fat diet significantly suppressed weight gain and fat mass. We investigated the composition of gut microbiota and explored its association with obesity-related markers. Results: Oral administration of L. paracasei AO356 significantly changed the gut microbiota and modified the relative abundance of Lactobacillus, Bacteroides, and Oscillospira. Bacteroides and Oscillospira were significantly related to the lipid metabolism pathway and obesity-related markers. We also confirmed the safety of L. paracasei AO356 using antibiotics resistance, hemolysis activity, bile salt hydrolase activity, lactate production, and toxicity tests following the safety assessment guidelines of the Ministry of Food and Drug Safety (MFDS). Discussion: This study demonstrated that L. paracasei AO356 is not only associated with an anti-obesity effect but also with changes in the gut microbiota and metabolic pathways related to obesity. Furthermore, the overall safety assessment seen in this study could increase the potential use of new probiotic materials with anti-obesity effects.

Discovery biomarker to optimize obeticholic acid treatment for non-alcoholic fatty liver disease.

The response rate to obeticholic acid (OCA), a potential therapeutic agent for non-alcoholic fatty liver disease, is limited. This study demonstrated that upregulation of the alternative bile acid synthesis pathway increases the OCA treatment response rate. The hepatic transcriptome and bile acid metabolite profile analyses revealed that the alternative bile acid synthesis pathway (Cyp7b1 and muricholic acid) in the OCA-responder group were upregulated compared with those in the OCA-non-responder group. Intestinal microbiome analysis also revealed that the abundances of Bacteroidaceae, Parabacteroides, and Bacteroides, which were positively correlated with the alternative bile acid synthesis pathway, were higher in the OCA-responder group than in the non-responder group. Pre-study hepatic mRNA levels of Cyp8b1 (classic pathway) were downregulated in the OCA-responder group. The OCA response rate increased up to 80% in cases with a hepatic Cyp7b1/Cyp8b1 ratio ≥ 5.0. Therefore, the OCA therapeutic response can be evaluated based on the Cyp7b1/Cyp8b1 ratio or the alternative/classic bile acid synthesis pathway activity.

Yijung-tang improves thermogenesis and reduces inflammation associated with gut microbiota in hypothyroid rats.

Currently, considerable attention is focused on exploring the potential relationship between herbal medicine (HM) and the gut microbiome in terms of thermoregulation, which is an important aspect of human health, in modern system biology. However, our knowledge of the mechanisms of HM in thermoregulation is inadequate. Here, we demonstrate that the canonical herbal formula, Yijung-tang (YJT), protects against hypothermia, hyperinflammation, and intestinal microbiota dysbiosis in PTU-induced hypothyroid rats. Notably, these properties were associated with alterations in the gut microbiota and signaling crosstalk between the thermoregulatory and inflammatory mediators in the small intestine and brown adipose tissue (BAT). In contrast to the conventional drug L-thyroxine for curing hypothyroidism, YJT has an efficacy for attenuating systematic inflammatory responses, related with depression in intestinal TLR4 and Nod2/Pglyrp1 signaling pathways. Our findings suggest that YJT could promote BAT thermogenesis and prevent systemic inflammation in PTU-induced hypothyroid rats, which was associated with its prebiotic effect on modulating of the gut microbiota and gene expression with relevance in the enteroendocrine function and innate immune systems. These findings may strengthen the rationale of the microbiota-gut-BAT axis for a paradigm shift to enable holobiont-centric medicine.

Faecalibacterium prausnitzii prevents hepatic damage in a mouse model of NASH induced by a high-fructose high-fat diet.

Introduction: Nonalcoholic steatohepatitis (NASH) is an advanced nonalcoholic fatty liver disease characterized by chronic inflammation and fibrosis. A dysbiosis of the gut microbiota has been associated with the pathophysiology of NASH, and probiotics have proven helpful in its treatment and prevention. Although both traditional and next-generation probiotics have the potential to alleviate various diseases, studies that observe the therapeutic effect of next-generation probiotics on NASH are lacking. Therefore, we investigated whether a next-generation probiotic candidate, Faecalibacterium prausnitzii, contributed to the mitigation of NASH. Methods: In this study, we conducted 16S rRNA sequencing analyses in patients with NASH and healthy controls. To test F. prausnitzii could alleviate NASH symptoms, we isolated four F. prausnitzii strains (EB-FPDK3, EB-FPDK9, EB-FPDK11, and EB-FPYYK1) from fecal samples collected from four healthy individuals. Mice were maintained on a high-fructose high-fat diet for 16 weeks to induce a NASH model and received oral administration of the bacterial strains. Changes in characteristic NASH phenotypes were assessed via oral glucose tolerance tests, biochemical assays, and histological analyses. Results: 16S rRNA sequencing analyses confirmed that the relative abundance of F. prausnitzii reduced significantly in patients with NASH compared to healthy controls (p < 0.05). In the NASH mice, F. prausnitzii supplementation improved glucose homeostasis, prevented hepatic lipid accumulation, curbed liver damage and fibrosis, restored damaged gut barrier functions, and alleviated hepatic steatosis and liver inflammation. Furthermore, real-time PCR assays documented that the four F. prausnitzii strains regulated the expression of genes related to hepatic steatosis in these mice. Discussion: Our study, therefore, confirms that the administration of F. prausnitzii bacteria can alleviate NASH symptoms. We propose that F. prausnitzii has the potential to contribute to the next-generation probiotic treatment of NASH.

Oral microbiome correlates with selected clinical biomarkers in individuals with no significant systemic disease.

The oral microbiome is an important component of the microbiome in the human body. Although the association of the oral microbiome with various diseases, including periodontitis and cancer, has been reported, information on how the oral microbiome is related to health-related indicators in healthy populations is still insufficient. In this study, we examined the associations of the oral microbiome with 15 metabolic and 19 complete blood count (CBC)-based markers in 692 healthy Korean individuals. The richness of the oral microbiome was associated with four CBC markers and one metabolic marker. Compositional variation in the oral microbiome was significantly explained by four markers: fasting glucose, fasting insulin, white blood cell count, and total leukocyte count. Furthermore, we found that these biomarkers were associated with the relative abundances of numerous microbial genera, such as Treponema, TG5, and Tannerella. By identifying the relationship between the oral microbiome and clinical biomarkers in a healthy population, our study presents a direction for future studies on oral microbiome-based diagnosis and interventions.

Modulation of gut microbiota by rice starch enzymatically modified using amylosucrase from Deinococcus geothermalis.

Amylosucrase can increase the amount of resistant starch (RS) in starch by transferring glucose from sucrose to amylopectin. Here, rice starch was modified using amylosucrase from Deinococcus geothermalis (DgAS). DgAS-modified rice starch (DMRS) increased the side-chain length of amylopectin and appeared in the form of B-type crystals. In vitro digestion analyses revealed that DMRS had a higher RS contents and lower digestion rate than native rice starch. When high-fat diet (HFD)-induced C57BL/6 mice were orally administered DMRS, body weight and white fat tissues of DMRS-fed HFD mice were not significantly different. However, serum leptin and glucose levels were significantly decreased and serum glucagon like peptide-1was increased in these mice. The cecal microbiome in DMRS-fed HFD mice was identified to investigate the role of DMRS in gut microbiota regulation. DMRS supplementation increased the relative abundance of Bacteroides, Faecalibaculum, and Ruminococcus in mouse gut microbiota. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01238-1.

Bacteroides faecium sp. nov. isolated from human faeces.

A novel bacterial strain, CBA7301T, was isolated from human faeces and was characterised using a polyphasic taxonomic approach. A phylogenetic analysis based on 16S rRNA gene sequences revealed that CBA7301T represented a member of the genus Bacteroides, in the family Bacteroidaceae. The similarity between the 16S rRNA gene sequence of CBA7301T and that of its most closely related species, Bacteroides faecichinchillae JCM 17102T, was 96.2 %, and the average nucleotide identity between these two strains was 77.9 %. The genome size was 6 782 182 bp, and the DNA G+C content was 42.5 mol%. Cells of CBA7301T were Gram-stain-negative, strictly anaerobic and rod-shaped. The optimal growth of this organism occurred at 30-35 °C, pH 7.0 and 0.5 % (w/v) NaCl. The respiratory quinone was menaquinone 10. The predominant polar lipids were phosphatidylethanolamine, phospholipids and aminophospholipids. The major cellular fatty acid was anteiso-C15 : 0. According to the results of the polyphasic taxonomic analysis, CBA7301T represents a novel species of the genus Bacteroides, which we named Bacteroides faecium sp. nov. The type strain is CBA7301T (=KCCM 43355T=ATCC TSD-227T).

Impact of the herbal medicine, Ephedra sinica stapf, on gut microbiota and body weight in a diet-induced obesity model.

Obesity is a chronic metabolic disease caused by excessive body fat and has become a global public health problem. Evidence suggests that obesity and obesity-induced metabolic disorders are closely related to gut microbiota. Bupropion (BP), an antidepressant medicine, and Ephedra sinica Stapf [Ephedraceae; Ephedrae Herba], a herbal medicine, are sympathetic stimulants and have weight loss effects. However, to our best knowledge, no studies have simultaneously assessed the effects of drugs and herbal medicines on obesity and gut microbiota. This study aimed to determine the effects of BP and ES on weight loss and re-modulation of host gut microbiota. To test this hypothesis, we fed C57BL/6J mice with a high-fat diet supplemented with bupropion (BP; 30 mg/kg/day) and Ephedra sinica Stapf extract (ES; 150 mg/kg/day) via oral gavage for eight weeks. Further, we evaluated the effects of BP and ES on body weight and fat accumulation. In addition, we evaluated the effects of BP and ES on gut microbiota using 16S rRNA amplicon sequencing. Our results showed that weight loss was confirmed in both BP and ES; however, it was more pronounced in ES. ES changed the overall composition of the gut microbiota by restoring the relative abundance of Oscillospiraceae, Lachnospiraceae, and the Firmicutes/Bacteroidetes ratio, an indicator of gut microbiota dysbiosis. Nine amplicon sequence variants (ASVs) of the gut microbiome were significantly recovered by BP and ES treatment, of which eight ASVs correlated with body weight and fat accumulation. Additionally, three ASVs were significantly recovered by ES treatment alone. In conclusion, the anti-obesity effects of BP and ES, especially fat accumulation, are related to the regulation of gut microbiota. Moreover, ES had a greater influence on the gut microbiota than BP.

Effects of sea salt intake on metabolites, steroid hormones, and gut microbiota in rats.

High salt intake is positively linked to many health problems, but the effect of mineral-rich sea salt (SS) has rarely been studied. To better understand the physiological effects of SS intake, the changes in general characteristics, metabolites, steroid hormones, and gut microbiota of SS-fed rats were investigated. Male rats were fed either a normal diet (ND, control) or ND containing 1% SS or 4% SS for 5 weeks. SS intake decreased fat, spleen, liver, and body weight, and increased blood urea nitrogen (BUN), water intake, and gut salt content. Accumulated gut salt content led to a decrease in beneficial bacteria, such as Lachnospiraceae and Lactobacillus, but an increase in potentially harmful bacteria, resulting in a change in lipid metabolites associated with gut health. Interestingly, most renal lysophosphatidylcholines (LPCs) associated with many renal functions were dramatically decreased and female hormones, such as estrogens, were significantly more altered than the male hormones by high SS intake. Although further investigation is needed, these data suggest that high SS intake could be positively linked to kidney dysfunction and gut health problems, and salt-related physiological changes may be sex-specific. Additionally, these data will be useful to better under-stand the physiological effects of SS intake.

Brachybacterium kimchii sp. nov. and Brachybacterium halotolerans subsp. kimchii subsp. nov., isolated from the Korean fermented vegetables, kimchi, and description of Brachybacterium halotolerans subsp. halotolerans subsp. nov.

Two Gram-stain-positive, oxidase-negative, catalase-positive, and coccus-shaped bacterial strains, designated CBA3104T and CBA3105T, were isolated from kimchi. Strain CBA3104T and CBA3105T grew at 10-35°C (optimum, 25°C and 30°C, respectively), at pH 6.0-8.5 (optimum, pH 6.5), and in the presence of 0-15% (w/v) NaCl (optimum, 5%). A phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CBA3104T formed a distinct phylogenetic lineage within the genus Brachybacterium whereas strain CBA3105T was closely positioned with Brachybacterium halotolerans MASK1Z-5T. The 16S rRNA gene sequence similarity between strains CBA3104T and CBA3105T was 99.9%, but ANI and dDDH values between strains CBA3104T and CBA3105T were 93.61% and 51.5%, respectively. Strain CBA3104T showed lower ANI and dDDH values than species delineation against three closely related strains and type species of the genus Brachybacterium, however, strain CBA3105T showed 96.63% ANI value and 69.6% dDDH value with Brachybacterium halotolerans MASK1Z-5T. Among biochemical analysis results, strain CBA3104T could uniquely utilize bromo-succinic acid whereas only strain CBA3105T was positive for alkaline phosphatase and α-fucosidase among two novel strains, closely related strains, and type species of the genus Brachybacterium. Compared with strain CBA3105T and Brachybacterium halotolerans JCM 34339T, strain CBA3105T was differentially positive for acid production of D-arabinose, D-adonitol, and potassium 5-ketogluconate and enzyme activity of ß-glucuronidase. Both strains contained menaquinone-7 as the dominant quinone. The cell-wall peptidoglycan of two novel strains contained meso-diaminopimelic acid. The major fatty acids of strains CBA3104T and CBA3105T were anteiso-C15:0, anteiso-C17:0, and iso-C16:0. The major polar lipids of both strains were phosphatidylglycerol and diphosphatidylglycerol. Strain CBA3104T possessed a uniquely higher abundance of tRNA (97 tRNAs) than four Brachybacterium strains used for comparative taxonomic analysis (54-62 tRNAs). Both the CBA3104T and CBA3105T strain harbored various oxidoreductase, transferase, hydrolase, and lyase as strain-specific functional genes compared to closely related strains and Brachybacterium type species. The results of biochemical/physiological, chemotaxonomic, and genomic analyses demonstrated that strains CBA3104T and CBA3105T represent a novel species of the genus Brachybacterium and a novel subspecies of B. halotolerans, respectively, for which the names Brachybacterium kimchii sp. nov. and B. halotolerans subsp. kimchii subsp. nov. are proposed. The type strains of the novel species and the novel subspecies are CBA3104T (= KCCM 43417T = JCM 34759T) and CBA3105T (= KCCM 43418T =JCM 34760T), respectively.