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.

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.

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.

Personalized Diets based on the Gut Microbiome as a Target for Health Maintenance: from Current Evidence to Future Possibilities.

Recently, the concept of personalized nutrition has been developed, which states that food components do not always lead to the same metabolic responses, but vary from person to person. Although this concept has been studied based on individual genetic backgrounds, researchers have recently explored its potential role in the gut microbiome. The gut microbiota physiologically communicates with humans by forming a bidirectional relationship with the micronutrients, macronutrients, and phytochemicals consumed by the host. Furthermore, the gut microbiota can vary from person to person and can be easily shifted by diet. Therefore, several recent studies have reported the application of personalized nutrition to intestinal microflora. This review provides an overview of the interaction of diet with the gut microbiome and the latest evidence in understanding the inter-individual differences in dietary responsiveness according to individual baseline gut microbiota and microbiome-associated dietary intervention in diseases. The diversity of the gut microbiota and the presence of specific microorganisms can be attributed to physiological differences following dietary intervention. The difference in individual responsiveness based on the gut microbiota has the potential to become an important research approach for personalized nutrition and health management, although further well-designed large-scale studies are warranted.

Renal transcriptome profiles in mice reveal the need for sufficient water intake irrespective of the drinking water type.

This study sought to characterize the impact of long-term dehydration in terms of physiological and biochemical parameters, as well as renal transcriptomes. Furthermore, we assessed whether consumption of specific types of water elicit more beneficial effects on these health parameters. To this end, C57BL/6 mice were either provided water for 15 min/day over 2 and 4 weeks (water restricted; RES), or ad libitum access to distilled (CON), tap, spring, or purified water. Results show that water restriction decreases urine output and hematocrit levels while increasing brain vasopressin mRNA levels in RES mice compared to control mice (CON). Meanwhile, blood urea nitrogen and creatinine levels were higher in the RES group compared to the CON group. Kidney transcriptome analysis further identified kidney damage as the most significant biological process modulated by dehydration. Mechanistically, prolonged dehydration induces kidney damage by suppressing the NRF2-signaling pathway, which targets the cytoprotective defense system. However, type of drinking water does not appear to impact physiological or blood biochemical parameters, nor the renal transcriptome profile, suggesting that sufficient water consumption is critical, irrespective of the water type. Importantly, these findings also inform practical action for environmental sustainability by providing a theoretical basis for reducing bottled water consumption.

Experiencing social exclusion changes gut microbiota composition.

Gut microbiota is suggested to regulate the host's mental health via the gut-brain axis. In this study, we investigated the relationship between the microbiome and psychological pain due to social exclusion. Adult individuals with (n = 14) and without (n = 25) social exclusion experience were assessed for the psychological status using self-reported questionnaires: Beck Anxiety Inventory (BAI), Beck Depression Inventory, and the UCLA Loneliness Scale. The gut microbiota was analyzed by 16 S rRNA gene sequencing and bioinformatics. The exclusion group had a 1.70-fold higher total BAI score and 2.16-fold higher levels of anxiety-related physical symptoms (p < 0.05). The gut microbial profiles also differed between the two groups. The exclusion group showed higher probability of having Prevotella-enriched microbiome (odds ratio, 2.29; 95% confidence interval, 1.65-2.75; p < 0.05), a significantly reduced Firmicutes/Bacteroidetes ratio, and decreased abundance of Faecalibacterium spp. (p < 0.05) which was associated with the duration and intensity of social exclusion (p < 0.05). Our results indicate that the psychological pain due to social exclusion is correlated with the gut microbiota composition, suggesting that targeting social exclusion-related microorganisms can be a new approach to solving psychological problems and related social issues.

Consumption of 85% cocoa dark chocolate improves mood in association with gut microbial changes in healthy adults: a randomized controlled trial.

Dark chocolate has long been recognized for its mood-altering properties; however, the evidence regarding the emotional effects of daily dark chocolate intake is limited. Therefore, we aimed to investigate the effects of dark chocolate intake on mood in everyday life, with special emphasis on the gut-brain axis. Two different dark chocolates (85% and 70% cocoa content) were tested in this study. In a randomized controlled trial, healthy adults (20-30 y) consumed either 30 g/d of 85% cocoa chocolate (DC85, n=18); 70% cocoa chocolate (DC70, n=16); or no chocolate (control group, CON; n=14); for 3 weeks. Mood states were measured using the Positive and Negative Affect Schedule (PANAS). Daily consumption of dark chocolate significantly reduced negative affect in DC85, but not in DC70. To assess the association between the mood-altering effects of dark chocolate and the gut microbiota, we performed fecal 16S rRNA sequencing analysis for the DC85 and CON groups. Gut microbial diversity was significantly higher in DC85 than CON (P<.05). Blautia obeum levels were significantly elevated and Faecalibacterium prausnitzii levels were reduced in DC85 compared to CON (P<.05). Furthermore, we found that the observed changes in negative affect scores were negatively correlated with diversity and relative abundance of Blautia obeum (P<.05). These findings indicate that dark chocolate exerts prebiotic effects, as evidenced by its ability to restructure the diversity and abundance of intestinal bacteria; thus, it may improve negative emotional states via the gut-brain axis.

Effect of Saengshik Supplementation on the Gut Microbial Composition of Healthy Korean Adults: A Single-Group Pilot Study.

Saengshik is a type of meal-replacement product or dietary supplement comprising an uncooked and dried plant-based food mixture with various health-promoting properties, such as antidiabetic, anti-dyslipidemic, antioxidant, and anticancer properties. Although these properties are considered attributable to the various bioactive components absorbed through the intestine and its remolding effect on intestinal microorganisms, the effect of Saengshik supplementation on gut microbiota profiles has not yet been studied. In this study, we investigated the effect of Saengshik administration on the composition of gut microbiota. This single-group design trial was conducted on 102 healthy men and women who received 40 g/day of Saengshik powder for 8 weeks, during which stool samples were collected at two fixed time points (baseline and the endpoint) for gut microbiota-profiling analysis. We observed a significant decrease in the α-diversity of gut microbiota after Saengshik consumption (P < 0.05), with significant changes identified in the composition of major microbial taxa, such as Bacteroidetes (P < 0.0001), Proteobacteria, Actinobacteria, and Verrucomicrobia (P < 0.0001). Notably, the gut microbial response was related to the inter-individual variability of habitual dietary intake and enterotype at baseline. To the best of our knowledge, this is the first study investigating the effects of Saengshik intake on changes in gut microbiota, with the results suggesting that individual habitual diet patterns and gut microbial shapes should be considered key aspects in Saengshik-mediated health-promotion effects.

Gut Microbiome Structure and Association with Host Factors in a Korean Population.

Characterizing the gut microbiome in the healthy population is the first step in elucidating its associations with host health conditions. Populations with different diet patterns, lifestyles, and genetic backgrounds harbor different gut microbes. In this study, we characterized the gut microbiome of 890 healthy Koreans using 16S rRNA sequencing. The Korean population harbored a relatively large fraction of the Prevotella enterotype and presented a distinctive gut microbiome, compared to that in the populations of other countries. Additionally, we determined the clusters of cooccurring microbes that were quantitatively correlated with each other. We found that microbe composition of the gut was strongly associated with age. We identified that the abundance of members of Bacteroidia and Clostridia differed with the host dietary patterns, body mass index, and stool frequency. The gut microbiome data obtained in this study would be an important resource for future studies addressing microbial contributions in health and disease. IMPORTANCE Comparing the gut microbiomes of healthy controls and disease patients showed that the composition of the gut microbiome is associated with various host health conditions. The gut microbiome in healthy Western populations is well characterized, while that of non-Western populations, with different diet patterns, lifestyles, and genetic backgrounds, is not clearly defined. In this study, we characterized the microbiome of 890 healthy Korean individuals using 16S rRNA sequencing and found that Koreans have a gut microbiome different from that in the individuals of neighboring countries. The members of Bacteroidetes and Firmicutes cooccurred and were quantitatively associated with each other. Additionally, we found that the gut microbial composition is strongly associated with the host's age. The microbiome data presented here represent the gut microbiome of a healthy Korean population and could be used to unveil gut microbiome-associated host conditions in this population.

Genome Analysis of Enterococcus mundtii Pe103, a Human Gut-Originated Pectinolytic Bacterium.

Pectin exists in significant amounts in vegetables and fruits as a component of the plant cell wall. In human diet, pectin is not degraded by the human digestive enzymes due to its complex structure; only gut bacteria degrade pectin in the large intestine. To date, although pectin is one of the most important sources of dietary fiber in human diet, there have been only few reports on human gut-originated pectinolytic bacteria. In this study, the strain Enterococcus mundtii Pe103, a bacterium with pectin-degrading activity, was isolated from the feces of a healthy Korean adult female. Culture experiments revealed that it could grow on pectin as the sole carbon source by degrading pectin to approximately 35% within 13 h. We report the complete genome data of human gut E. mundtii Pe103. It consists of a circular chromosome (3,084,146 bps) and two plasmids (63,713 and 56,223 bps). Genomic analysis suggested that at least nine putative enzymes related to pectin degradation are present in E. mundtii Pe103. These enzymes may be involved in the degradation of pectin. The whole genome information of E. mundtii Pe103 could improve the understanding of the mechanism underlying the degradation of pectin by human gut microbiota.

Gut microorganisms and their metabolites modulate the severity of acute colitis in a tryptophan metabolism-dependent manner.

PURPOSE: Growing evidence shows that nutrient metabolism affects inflammatory bowel diseases (IBD) development. Previously, we showed that deficiency of indoleamine 2,3-dioxygenase 1 (Ido1), a tryptophan-catabolizing enzyme, reduced the severity of dextran sulfate sodium (DSS)-induced colitis in mice. However, the roles played by intestinal microbiota in generating the differences in disease progression between Ido1+/+ and Ido1-/- mice are unknown. Therefore, we aimed to investigate the interactions between the intestinal microbiome and host IDO1 in governing intestinal inflammatory responses. METHODS: Microbial 16s rRNA sequencing was conducted in Ido1+/+ and Ido1-/- mice after DSS treatment. Bacteria-derived tryptophan metabolites were measured in urine. Transcriptome analysis revealed the effects of the metabolite and IDO1 expression in HCT116 cells. Colitis severity of Ido1+/+ was compared to Ido1-/- mice following fecal microbiota transplantation (FMT). RESULTS: Microbiome analysis through 16S-rRNA gene sequencing showed that IDO1 deficiency increased intestinal bacteria that use tryptophan preferentially to produce indolic compounds. Urinary excretion of 3-indoxyl sulfate, a metabolized form of gut bacteria-derived indole, was significantly higher in Ido1-/- than in Ido1+/+ mice. Transcriptome analysis showed that tight junction transcripts were significantly increased by indole treatment in HCT116 cells; however, the effects were diminished by IDO1 overexpression. Using FMT experiments, we demonstrated that bacteria from Ido1-/- mice could directly attenuate the severity of DSS-induced colitis. CONCLUSIONS: Our results provide evidence that a genetic defect in utilizing tryptophan affects intestinal microbiota profiles, altering microbial metabolites, and colitis development. This suggests that the host and intestinal microbiota communicate through shared nutrient metabolic networks.

Differential Effects of Typical Korean Versus American-Style Diets on Gut Microbial Composition and Metabolic Profile in Healthy Overweight Koreans: A Randomized Crossover Trial.

The Westernized diet has been associated with the pathogenesis of metabolic diseases, whereas a Korean diet has been reported to exert beneficial effects on health in several studies. However, the effects of Western and Korean diets on the gut microbiome and host metabolome are unclear. To examine the diet-specific effects on microbiome and metabolome, we conducted a randomized crossover clinical trial of typical Korean diet (TKD), typical American diet (TAD), and recommended American diet (RAD). The trial involved a 4-week consumption of an experimental diet followed by a 2-week interval before diet crossover. 16S rRNA sequencing analysis identified 16, 10, and 14 differential bacteria genera specific to TKD, RAD, and TAD, respectively. The Firmucutes-Bacteroidetes ratio was increased by TKD. Nuclear magnetic resonance metabolome profiling revealed that TKD enriched branched chain amino acid metabolism, whereas ketone body metabolism was evident in RAD and TAD. Microbiome and metabolome responses to the experimental diets varied with individual enterotypes. These findings provide evidence that the gut microbiome and host metabolome rapidly respond to different cultural diets. The findings will inform clarification of the diet-related communication networks of the gut microbiome and host metabolome in humans.

Serum level of sex steroid hormone is associated with diversity and profiles of human gut microbiome.

Gut microbiota plays roles in host physiology including endocrine function. Although some data suggest a potential connection between biological sex differences and gut microbiota, the connection between sex steroid hormones and gut microbes remained unexplored. The current study investigates the relationship between gut microbes and serum levels of testosterone in men and estradiol in women. Fecal microbiota from a total of 57 men (n = 31) and women (n = 26) were assessed using 16s rRNA gene sequencing. Based on the levels of serum testosterone and estradiol in men and women, respectively, participants were stratified into three groups of Low, Medium, and High. Microbiome communities were analyzed as a function of the steroid hormone within sex. Men and women in the High group harbored more diverse gut microbial communities than others. In men, the abundance of Acinetobacter, Dorea, Ruminococcus, and Megamonas correlated significantly with testosterone levels. Women in the High group have more Bacteroidetes and less Firmicutes phyla than those in the Low group. Genera Slackia and Butyricimonas were significantly correlated with estradiol levels. These results demonstrate that sex steroid hormone levels are correlated with diversity and gut microbial composition, and provide fundamental information helpful for developing communication networks between human and microbial communities.

Single-Factor SOX2 Mediates Direct Neural Reprogramming of Human Mesenchymal Stem Cells via Transfection of In Vitro Transcribed mRNA.

Neural stem cells (NSCs) are a prominent cell source for understanding neural pathogenesis and for developing therapeutic applications to treat neurodegenerative disease because of their regenerative capacity and multipotency. Recently, a variety of cellular reprogramming technologies have been developed to facilitate in vitro generation of NSCs, called induced NSCs (iNSCs). However, the genetic safety aspects of established virus-based reprogramming methods have been considered, and non-integrating reprogramming methods have been developed. Reprogramming with in vitro transcribed (IVT) mRNA is one of the genetically safe reprogramming methods because exogenous mRNA temporally exists in the cell and is not integrated into the chromosome. Here, we successfully generated expandable iNSCs from human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) via transfection with IVT mRNA encoding SOX2 (SOX2 mRNA) with properly optimized conditions. We confirmed that generated human UCB-MSC-derived iNSCs (UM-iNSCs) possess characteristics of NSCs, including multipotency and self-renewal capacity. Additionally, we transfected human dermal fibroblasts (HDFs) with SOX2 mRNA. Compared with human embryonic stem cell-derived NSCs, HDFs transfected with SOX2 mRNA exhibited neural reprogramming with similar morphologies and NSC-enriched mRNA levels, but they showed limited proliferation ability. Our results demonstrated that human UCB-MSCs can be used for direct reprogramming into NSCs through transfection with IVT mRNA encoding a single factor, which provides an integration-free reprogramming tool for future therapeutic application.

Generation of patient specific human neural stem cells from Niemann-Pick disease type C patient-derived fibroblasts.

Niemann-Pick disease type C (NPC) is a neurodegenerative and lysosomal lipid storage disorder, characterized by the abnormal accumulation of unesterified cholesterol and glycolipids, which is caused by mutations in the NPC1 genes. Here, we report the generation of human induced neural stem cells from NPC patient-derived fibroblasts (NPC-iNSCs) using only two reprogramming factors SOX2 and HMGA2 without going through the pluripotent state. NPC-iNSCs were stably expandable and differentiated into neurons, astrocytes, and oligodendrocytes. However, NPC-iNSCs displayed defects in self-renewal and neuronal differentiation accompanied by cholesterol accumulation, suggesting that NPC-iNSCs retain the main features of NPC. This study revealed that the cholesterol accumulation and the impairments in self-renewal and neuronal differentiation in NPC-iNSCs were significantly improved by valproic acid. Additionally, we demonstrated that the inhibition of cholesterol transportation by U18666A in WT-iNSCs mimicked the impaired self-renewal and neuronal differentiation of NPC-iNSCs, indicating that the regulation of cholesterol homeostasis is a crucial determinant for the neurodegenerative features of NPC. Taken together, these findings suggest that NPC-iNSCs can serve as an unlimited source of neural cells for pathological study or drug screening in a patient specific manner. Furthermore, this direct conversion technology might be extensively applicable for other human neurodegenerative diseases.

Direct Conversion of Human Umbilical Cord Blood into Induced Neural Stem Cells with SOX2 and HMGA2.

Recent advances have shown the direct reprogramming of mouse and human fibroblasts into induced neural stem cells (iNSCs) without passing through an intermediate pluripotent state. Thus, direct reprogramming strategy possibly provides a safe and homogeneous cellular platform. However, the applications of iNSCs for regenerative medicine are limited by the restricted availability of cell sources. Human umbilical cord blood (hUCB) cells hold great potential in that immunotyped hUCB units can be immediately obtained from public banks. Moreover, hUCB samples do not require invasive procedures during collection or an extensive culture period prior to reprogramming. We recently reported that somatic cells can be directly converted into iNSCs with high efficiency and a short turnaround time. Here, we describe the detailed method for the generation of iNSCs derived from hUCB (hUCB iNSCs) using the lineage-specific transcription factors SOX2 and HMGA2. The protocol for deriving iNSC-like colonies takes 1∼2 weeks and establishment of homogenous hUCB iNSCs takes additional 2 weeks. Established hUCB iNSCs are clonally expandable and multipotent producing neurons and glia. Our study provides an accessible method for generating hUCB iNSCs, contributing development of in vitro neuropathological model systems.

Inhibition by miR-410 facilitates direct retinal pigment epithelium differentiation of umbilical cord blood-derived mesenchymal stem cells.

Retinal pigment epithelium (RPE) is a major component of the eye. This highly specialized cell type facilitates maintenance of the visual system. Because RPE loss induces an irreversible visual impairment, RPE generation techniques have recently been investigated as a potential therapeutic approach to RPE degeneration. A microRNA-based technique is a new strategy for producing RPE cells from adult stem cell sources. Previously, we identified that antisense microRNA-410 (anti-miR-410) induces RPE differentiation from amniotic epithelial stem cells. In this study, we investigated RPE differentiation from umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) via anti-miR-410 treatment. We identified miR-410 as a RPE-relevant microRNA in UCB-MSCs from among 21 putative human RPE-depleted microRNAs. Inhibition of miR-410 induces overexpression of immature and mature RPE-specific factors, including MITF, LRAT, RPE65, Bestrophin, and EMMPRIN. The RPE-induced cells were able to phagocytize microbeads. Results of our microRNA-based strategy demonstrated proof-of-principle for RPE differentiation in UCB-MSCs by using anti-miR-410 treatment without the use of additional factors or exogenous transduction.

Human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis via regulation of B lymphocyte maturation.

Mesenchymal stem cell (MSC) has been applied for the therapy of allergic disorders due to its beneficial immunomodulatory abilities. However, the underlying mechanisms for therapeutic efficacy are reported to be diverse according to the source of cell isolation or the route of administration. We sought to investigate the safety and the efficacy of human adipose tissue-derived MSCs (hAT-MSCs) in mouse atopic dermatitis (AD) model and to determine the distribution of cells after intravenous administration. Murine AD model was established by multiple treatment of Dermatophagoides farinae. AD mice were intravenously infused with hAT-MSCs and monitored for clinical symptoms. The administration of hAT-MSCs reduced the gross and histological signatures of AD, as well as serum IgE level. hAT-MSCs were mostly detected in lung and heart of mice within 3 days after administration and were hardly detectable at 2 weeks. All of mice administered with hAT-MSCs survived until sacrifice and did not demonstrate any adverse events. Co-culture experiments revealed that hAT-MSCs significantly inhibited the proliferation and the maturation of B lymphocytes via cyclooxygenase (COX)-2 signaling. Moreover, mast cell (MC) degranulation was suppressed by hAT-MSC. In conclusion, the intravenous infusion of hAT-MSCs can alleviate AD through the regulation of B cell function.

Lifestyle and geographic insights into the distinct gut microbiota in elderly women from two different geographic locations.

BACKGROUND: A large number of microorganisms reside within the gastrointestinal tract, especially in the colon, and play important roles in human health and disease. The composition of the human gut microbiota is determined by intrinsic host factors and environmental factors. While investigating environmental factors to promote human health is of great interest, few studies have focused on their effect on the gut microbiota. This study aimed to investigate differences in gut microbiota composition according to lifestyle and geographical area, even in people with similar genetic background. METHODS: We enrolled ten and nine elderly women in their seventies from island and inland areas, respectively. Fecal samples were obtained from individuals, and bacterial 16S ribosomal RNA genes were analyzed by next-generation sequencing to define the gut microbiota composition. We assessed their diet, which can influence the gut microbial community. We also conducted physical examination and determined the physical activity levels of the subjects. RESULTS: The inland subjects had a significantly higher rectal temperature, systolic blood pressure, and heart rate and a significantly lower physical activity score than the island subjects. Fecal samples from the island group showed a tendency to have greater microbial diversity than those from the inland group. Interestingly, the microbial community composition differed significantly between the two groups. Catenibacterium was enriched in subjects from the island area. Catenibacterium showed a negative correlation with rectal temperature and a positive correlation with the dietary level of animal fat. In contrast, Butyricimonas was enriched in the inland subjects. A positive correlation was found between Butyricimonas and mean arterial pressure. CONCLUSIONS: This study identified differences in the gut microbiota composition between elderly women from different parts of South Korea, and our findings suggest that further studies of the human gut microbiota should evaluate aspects of the living environment.