Young-Do Nam

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease, and its global incidence continues to increase. MASLD can progress from simple steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. However, effective preventive and therapeutic options remain limited. In this study, obeticholic acid (OCA) and the probiotic mixture VSL#3 were co-administered to a mouse model of MASLD to modulate gut microbiota and bile acid metabolism. Methods: Male C57BL/6 mice were fed a WD to induce MASLD and treated with OCA, VSL#3, or both. Gut microbiota was analyzed by 16S rRNA sequencing, bile acid (BA) composition was assessed by LC–MS/MS, hepatic and intestinal gene expression was determined by quantitative real-time PCR (qPCR) and immunohistochemistry, and unconjugated OCA pharmacokinetics (PK) were evaluated. Results: VSL#3-containing groups showed differences in selected taxa with reported bile salt hydrolase (BSH) potential and in BA composition, including a numerical shift toward higher levels of deconjugated BAs. Co-administration of OCA and VSL#3 was accompanied by lower hepatic steatosis, numerically favorable serum markers of liver injury, and lower cholesterol and total bilirubin levels. In addition, mice receiving VSL#3 showed numerically higher early plasma concentrations of unconjugated OCA. Lower intestinal ATP-binding cassette subfamily C member 2 (Abcc2) expression was also observed as a separate exploratory finding. Conclusions: The co-administration of VSL#3 with OCA was accompanied by exploratory differences in selected biological parameters and early-phase unconjugated OCA exposure. Lower intestinal Abcc2/Mrp2 expression was observed as a separate exploratory finding, and no functional relationship between intestinal transporter expression and OCA pharmacokinetics was established.

Purpose This study investigated the association between plant-based diet quality and gut microbiota and explored whether integrating microbiota profiles with dietary indices improved strength of association with selected cardiometabolic outcomes. Methods In this cross-sectional study, we analyzed cohort data collected from 2,388 Korean adults between 2017 and 2019. Dietary quality indices, including the overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI), were derived from a food frequency questionnaire. Gut microbiota were profiled using 16S rRNA gene sequencing. Cardiometabolic risk factors included obesity, abdominal obesity, elevated fasting glucose, elevated triglycerides, low high-density lipoprotein cholesterol (HDL-C), and elevated blood pressure. Results A higher hPDI score was associated with reduced obesity risk (OR = 0.72; 95% CI, 0.57–0.91) and improved gut microbiota α-diversity. A higher uPDI score was associated with increased risk of elevated fasting glucose (OR = 1.23; 95% CI, 1.00–1.52) and low HDL-C levels (OR = 1.35; 95% CI, 1.07–1.70), and lower α-diversity. hPDI and uPDI scores were also associated with differences in gut microbial community structure. For obesity and elevated fasting glucose, models integrating plant-based diet indices with gut microbiome features showed higher area under the curve than dietary-only models. Genus-level analyses identified key bacterial genera associated with dietary scores and metabolic traits. The predictive performance for low HDL-C remained modest across models. Conclusions Plant-based diet quality was associated with gut microbiota composition and cardiometabolic health. Integrating gut microbiome features with dietary assessments provided greater explanatory value for obesity and elevated fasting glucose, although longitudinal studies are needed to clarify temporal relationships and causal pathways.

Journal of Animal Science and Technology (JAST) is a peer-reviewed, open access journal publishing original research, review articles and notes in all fields of animal science. Topics covered by the journal include: genetics and breeding, physiology, nutrition of monogastric animals, nutrition of ruminants, animal products (milk, meat, eggs and their by-products) and their processing, grasslands and roughages, livestock environment, animal biotechnology, animal behavior and welfare.

Dyspepsia is a prevalent refractory condition that arises from various causes and lacks definitive treatment. There is an urgent need for evidence to support the use of herbal medicines in the treatment of gastroenterological disorders. This study aimed to compare the therapeutic effects of two common herbal formulas—namely, Shihosogan-tang (SST) and Yijung-tang (YJT)—on loperamide (LOP)-induced dyspepsia and to explore their potential mechanisms. A dyspepsia model was established using Sprague–Dawley rats by intraperitoneal LOP injection at a dose of 3 mg/kg/day for one week. During this period, 30% ethanol extract of SST (1.4 g/kg/day) or YJT (2 g/kg/day) was intragastrically administered in rats. Mosapride (3 mg/kg/day) was used as the positive control. Unlike YJT, SST significantly mitigated LOP-induced reductions in intestinal length, gastrointestinal transit ratio, and serum ghrelin levels. Conversely, YJT significantly enhanced defecation, ileum villus length, and muscular thickness, outperforming SST. Expression of genes related to intestinal motility (ZO-1), inflammation (IL-6), and water absorption (SERT, AQP-3) indicated that both treatments ameliorated LOP-induced changes in the duodenum. Additionally, neuropeptides and hormones (TRH, bombesin, motilin, glucagon, neurotensin, PYY), Toll-like receptors (TLR-2 and TLR-4), and growth factors (GDNF and BMP2) were noticeably altered by SST and/or YJT treatment. While neither LOP nor the herbal formulas affected gut microbiota α-diversity, SST and YJT altered β-diversity compared to LOP alone, unlike mosapride. SST improves dyspepsia more effectively than YJT, possibly through mechanisms involving intestinal hormone regulation, inflammation inhibition, and gut microbiota modulation.

The gut microbiome is crucial for human health maintenance and disease development, yet limited understanding of its structure and maintenance hinders effective microbiome-based health improvement strategies. We investigated gut microbiome compositional patterns in healthy Koreans (n = 890), identifying six clusters (I–VI) with unique compositions and host preferences. Each cluster had a distinct topological structure within the microbial interaction network, underscoring its diverse roles in maintaining microbial communities. Cluster II, predominated by Bacteroides and Faecalibacterium, was consistently found across individuals and centrally located within the microbial interaction network. Cluster III, mainly composed of Oscillospira and Coprococcus, and IV, dominated by Enterobacteriaceae and Bacteroides fragilis, demonstrated mutually exclusive relationships, reflecting affinities for host clusters with varied dietary patterns and microbial diversity. Clusters V and VI linked different microbial clusters, and cluster I had separate subcommunities. This study reveals intricate structures and interactions within microbial communities, offering insights into the gut microbiome ecology and guiding health enhancement strategies.

Akkermansia muciniphila, a promising candidate for next-generation probiotics, exhibits significant genomic diversity, classified into several distinct clades (AmI to AmIV). Notably, a single Akkermansia clade tends to predominate within individual hosts, with co-occurrence of different clades being rare. The mechanisms driving such clade-specific exclusion remain unclear. Here, we show that extracellular vesicles (EVs) derived from AmII clade inhibit the growth of clade I (AmI), conferring a competitive advantage to AmII. Moreover, we observe clade-specific immunoglobulin A (IgA) responses, where AmII clade-specific IgAs, induced by EVs from AmII, facilitate niche occupancy and competitive exclusion of AmI. These findings provide insights into the competitive dynamics of A. muciniphila clades and suggest that future personalized microbiome interventions could be optimized by considering the clade composition of A. muciniphila in individual hosts.

Immunotherapy, especially immune checkpoint inhibitor (ICI) therapy, has yielded remarkable outcomes for some patients with solid cancers, but others do not respond to these treatments. Recent research has identified the gut microbiota as a key modulator of immune responses, suggesting that its composition is closely linked to responses to ICI therapy in cancer treatment. As a result, the gut microbiome is gaining attention as a potential biomarker for predicting individual responses to ICI therapy and as a target for enhancing treatment efficacy. In this review, we discuss key findings from human observational studies assessing the effect of antibiotic use prior to ICI therapy on outcomes and identifying specific gut bacteria associated with favorable and unfavorable responses. Moreover, we review studies investigating the possibility of patient outcome prediction using machine learning models based on gut microbiome data before starting ICI therapy and clinical trials exploring whether gut microbiota modulation, for example via fecal microbiota transplantation or live biotherapeutic products, can improve results of ICI therapy in patients with cancer. We also briefly discuss the mechanisms through which the gut microbial-derived products influence immunotherapy effectiveness. Further research is necessary to fully understand the complex interactions between the host, gut microbiota, and immunotherapy and to develop personalized strategies that optimize responses to ICI therapy.

Young In Kim, Eun-Ji Song, Ji-Eun Eom, Hee Soon Shin, Gun-Dong Kim, Young-Do Nam, and So-Young Lee. Journal of the Korean Society of Food Science and Nutrition 2024;53:1127-34. https://doi.org/10.3746/jkfn.2024.53.11.1127

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.

Sang Hoon Kim, Yura Choi, Jihong Oh, Eui Yeon Lim, Jung Eun Lee, Eun-Ji Song, Young-Do Nam, Hojun Kim. Gut and Liver 2024;18:621-31. https://doi.org/10.5009/gnl230130