• Journal of Microbiology and Biotechnology
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• v.32 no.6
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• pp.699-708
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• 2022

Antibiotic exposure during pregnancy have an adversely effects on offspring behavior and development. However, its mechanism is still poorly understood. To uncover this, we added ceftriaxone sodium to the drinking water of rats during pregnancy and conducted three-chamber sociability test, open-field test, and Morris water maze test in 3- and 6-week-old offspring. The antibiotic group offspring showed lower sociability and spatial learning and memory than control. To determine the role of the gut microbiota and their metabolites in the changes in offspring behavior, fecal samples of 6-week-old offspring rats were sequenced. The composition of dominant gut microbial taxa differed between the control and antibiotic groups. KEGG pathway analysis showed that S24-7 exerted its effects through the metabolic pathways including mineral absorption, protein digestion and absorption, Valine, leucine, and isoleucine biosynthesis. Correlation analysis showed that S24-7 abundance was negatively correlated with the level of VEGF, and metabolites associated with S24-7-including 3-aminobutanoic acid, dacarbazine, L-leucine, 3-ketosphinganine, 1-methylnicotinamide, and N-acetyl-L-glutamate-were also significantly correlated with VEGF levels. The findings suggest that antibiotic exposure during pregnancy, specifically ceftriaxone sodium, will adversely affects the behavior of offspring rats due to the imbalance of gut microbiota, especially S24-7, via VEGF and various metabolic pathways.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.2
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• pp.153-164
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• 2024

This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control. Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 10¹¹ colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5-6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.

• Journal of Microbiology and Biotechnology
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• v.34 no.6
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• pp.1214-1221
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• 2024

The accumulating evidence substantiates the indispensable role of gut microbiota in modulating the pathogenesis of type 2 diabetes. Uncovering the intricacies of the mechanism is imperative in aiding disease control efforts. Revealing key bacterial species, their metabolites and/or metabolic pathways from the vast array of gut microorganisms can significantly contribute to precise treatment of the disease. With a high prevalence of type 2 diabetes in Inner Mongolia, China, we recruited volunteers from among the Mongolian population to investigate the relationship between gut microbiota and the disease. Fecal samples were collected from the Volunteers of Mongolia with Type 2 Diabetes group and a Control group, and detected by metagenomic analysis and untargeted metabolomics analysis. The findings suggest that Firmicutes and Bacteroidetes phyla are the predominant gut microorganisms that exert significant influence on the pathogenesis of type 2 diabetes in the Mongolian population. In the disease group, despite an increase in the quantity of most gut microbial metabolic enzymes, there was a concomitant weakening of gut metabolic function, suggesting that the gut microbiota may be in a compensatory state during the disease stage. β-Tocotrienol may serve as a pivotal gut metabolite produced by gut microorganisms and a potential biomarker for type 2 diabetes. The metabolic biosynthesis pathways of ubiquinone and other terpenoid quinones could be the crucial mechanism through which the gut microbiota regulates type 2 diabetes. Additionally, certain Clostridium gut species may play a pivotal role in the progression of the disease.

• Korean Journal of Microbiology
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• v.49 no.2
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• pp.156-164
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• 2013

Actinomycetes produce diverse secondary metabolites which have the primary importance in medicine, agriculture and food production, and key to this is their ability to interact with other organisms in natural habitats. In this study, we have investigated the taxonomical and functional diversity of actinomycetes in fecal sample of rhinoceros beetle larvae (Allomyrina dichotoma L.) by using culture-dependent and -independent approaches. For the culture-independent approach, the community DNA was extracted from the sample and 16S rRNA genes of actinomycetes were amplified using actinomycetes-specific PCR primers. Thirty-seven clones were classified into 15 genera and 24 species of actinomycetes. For the culture-dependent approach, 53 strains were isolated from larval feces, of which 27 isolates were selected based on morphological characteristics. The isolates were classified into 4 genera and 14 species, and 24 isolates (89%) were identified as the genus Streptomyces. Many of the representative isolates had antimicrobial activities against plant pathogenic fungi and Gram-positive bacteria. In addition, most of the isolates (78%) showed biochemical properties to hydrolyze cellulose and casein. The results demonstrated that diverse and valuable actinomycetes could be isolated from insect fecal samples, indicating that insect guts can be rich sources for novel bioactive compounds.

• Journal of Food Hygiene and Safety
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• v.29 no.2
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• pp.85-91
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• 2014

Deoxynivalenol (DON) and related trichothecene mycotoxins are extensively distributed in the cereal-based food and feed stuffs worldwide. Recent climate changes and global grain trade increased chance of exposure to more DON and related toxic metabolites in poorly managed production systems. Monitoring the biological and environmental exposures to the toxins are crucial in protecting human and animals from toxicities of the hazardous contaminants in food or feeds. Exposure biomarkers including urine DON itself are prone to shift to less harmful metabolites by intestinal microbiota and liver metabolic enzymes. De-epoxyfication of DON by gut microbes such as Eubacterium strain BBSH 797 and Eubacterium sp. DSM 11798 leads to more fecal secretion of DOM-1. By contrast, most of plant-derived DON-glucoside is also easily catabolized to free DON by gut microbes, which produces more burden to body. Phase 2 hepatic metabolism also contributes to the glucuronidation of DON, which can be useful urine biomarkers. However, chemical modification could be very typical depending on the anthropologic or genetic background, luminal bacteria, and hepatic metabolic enzyme susceptibility to the toxins in the diet. After toxin exposure, effect biomarkers are also important in estimating the linkage and mechanisms of foodborne diseases in human and animal population. Most prominent adverse effects are demonstrated in the DON-induced immunological and behavioral disorders. For instance, acutely elevated interleukin-8 from insulted gut exposed to dietaty DON is a dominant clinical biomarker in human and animals. Moreover, subchronic exposure to the toxins is associated with high levels of serum IgA, a biological mediator of IgA nephritis. In particular, anorexia monitoring using mouse models are recently developed to monitor the biological activities of DON-induced feed refusal. It is also mechanistically linked to alteration of serotoin and peptide YY, which are promising biomarkers of neurological disorders by the toxins. As animal-alternative biomonitoring, huamn enterocyte-based assay has been developed and more realistic gut mimetic models would be useful in monitoring the effect biomarkers in resposne to toxic contaminants in the future investigations.

• Korean Journal of Acupuncture
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• v.40 no.3
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• pp.109-127
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• 2023

Objectives : It was conducted to experimentally analyze the effects of acupuncture treatment at CV12, ST25, and ST36 on weight, FBCS, fat metabolism, microbiome, and metabolome changes in the general diet rat and the high-fat diet rat. Methods : It was classified into four groups: general diet & non-treatment group (ND), general diet & acupuncture treatment group (ND+AT), high-fat diet & non-treatment group (HFD), and high-fat diet & acupuncture treatment group (HFD-AT). After acupuncture treatment was performed on CV12, ST25, and ST36, changes in body weight, FBCS, fat metabolism, microbiome, and metabolome were analyzed. Results : Compared to the ND group, acupuncture treatment performed on CV12, ST25, and ST36 in the ND+AT group had no significant effect. Compared to the HFD group, CV12, ST25, and ST36 acupuncture in the HFD+AT group reduced weight, fat weight, inflammatory cytokine IL-6 expression, and lipid droplet accumulation in liver tissue. Acupuncture can promote fat metabolism and relieve inflammatory conditions. Differences in diversity between ND and HFD groups were clear in changes in microbiome, fecal metabolites, and serum metabolites. As a result of some microbiome and metabolites involved in fat decomposition, intestinal lipid absorption, and blood lipid concentration control, such as Intestinimonas, Ruminococcus 1, pyroglutamic acid, tryptophan, and inositol, it was observed that the acupuncture treatment effect was evident in the disease-induced imbalance. Conclusions : Acupuncture treatment performed on CV12, ST25, ST36 clearly observed various regulatory actions on obesity induced by high-fat diet, confirming that the action of acupuncture treatment mainly plays a role in controlling an unbalanced state.

• BMB Reports
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• v.56 no.7
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• pp.404-409
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• 2023

This study investigates the relationship between cancer cachexia and the gut microbiota, focusing on the influence of cancer on microbial composition. Lewis lung cancer cell allografts were used to induce cachexia in mice, and body and muscle weight changes were monitored. Fecal samples were collected for targeted metabolomic analysis for short chain fatty acids and microbiome analysis. The cachexia group exhibited lower alpha diversity and distinct beta diversity in gut microbiota, compared to the control group. Differential abundance analysis revealed higher Bifidobacterium and Romboutsia, but lower Streptococcus abundance in the cachexia group. Additionally, lower proportions of acetate and butyrate were observed in the cachexia group. The study observed that the impact of cancer cachexia on gut microbiota and their generated metabolites was significant, indicating a host-to-gut microbiota axis.

• The Korean journal of internal medicine
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• v.39 no.5
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• pp.746-758
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• 2024

The emerging field of gut-lung axis research has revealed a complex interplay between the gut microbiota and respiratory health, particularly in asthma. This review comprehensively explored the intricate relationship between these two systems, focusing on their influence on immune responses, inflammation, and the pathogenesis of respiratory diseases. Recent studies have demonstrated that gut microbiota dysbiosis can contribute to asthma onset and exacerbation, prompting investigations into therapeutic strategies to correct this imbalance. Probiotics and prebiotics, known for their ability to modulate gut microbial compositions, were discussed as potential interventions to restore immune homeostasis. The impact of antibiotics and metabolites, including short-chain fatty acids produced by the gut microbiota, on immune regulation was examined. Fecal microbiota transplantation has shown promise in various diseases, but its role in respiratory disorders is not established. Innovative approaches, including mucus transplants, inhaled probiotics, and microencapsulation strategies, have been proposed as novel therapeutic avenues. Despite challenges, including the sophisticated adaptability of microbial communities and the need for mechanistic clarity, the potential for microbiota-based interventions is considerable. Collaboration between researchers, clinicians, and other experts is essential to unravel the complexities of the gut-lung axis, paving a way for innovative strategies that could transform the management of respiratory diseases.

• Journal of Microbiology and Biotechnology
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• v.34 no.9
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• pp.1769-1777
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• 2024

Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect related to activation of substance P (SP). SP activation can result from dysregulation of the gut-brain axis, and also from activation of protein kinase A signaling (PKA) signaling. In this study, we connected these factors in an attempt to unveil the mechanisms underlying CINV and develop new therapeutic strategies. Female rats were injected with cisplatin (Cis) to induce pica. Fecal samples were collected before/after injection, and subjected to lipid metabolomics analysis. In another portion of pica rats, the PKA inhibitor KT5720 was applied to investigate the involvement of PKA signaling in CINV, while fecal microbiota transplantation (FMT) was implemented to verify the therapeutic effect of the lipid metabolite 14(15)-EpETE. Pica symptoms were recorded, followed by ileal histological examination. The targeting relationship between 14(15)-EpETE and glucagon was determined by bioinformatics. SP and glucagon/PKA signaling in rat ileum, serum, and/or brain substantia nigra were detected by immunohistochemistry, enzyme-linked immunosorbent assay, and/or western blot. The results showed a significantly lower level of 14(15)-EpETE in rat feces after Cis injection. KT5720 treatment alleviated Cis-induced pica symptoms, ileal injury, SP content increase in the ileum, serum, and brain substantia nigra, and ileal PKA activation in rats. The ileal level of glucagon was elevated by Cis in rats. FMT exerted an effect similar to that of KT5720 treatment, relieving the Cis-induced changes, including ileal glucagon/PKA activation in rats. Our findings demonstrate that FMT restores 14(15)-EpETE production, which inhibits SP release by targeting GCG/PKA signaling, ultimately mitigating CINV.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.8
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• pp.1137-1144
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• 2019

Objective: This experiment was designed to evaluate the effects of Agave tequilana inulin and Lactobacillus casei (L. casei) on growth performace, hematological variables, serum metabolites, and total coliforms in nursing lambs. Methods: The experimental design was completely randomized; treatments were T1, control (pre-starter concentrate, PC), T2: T1+2% inulin, and T3: T1+2% inulin+L. casei; treatments were compared with Tukey test ($p{\leq}0.05$); and 45 new born $Kathadin{\times}Dorset lambs$ ($4.8{\pm}0.8kg$ birth weight) were the experimental units (15 per treatment). The variables were daily weight gain (DWG), dry matter intake and diarrheas incidence (%) during 56 d. Twenty-four hours after birth and at the end of the experiment, blood samples were collected to evaluate hematological variables and serum metabolites. Besides, the populations of total coliforms and lactobacilli were estimated in fecal samples. Results: Addition of agave inulin and L. casei increased ($p{\leq}0.05$) DWG 356, 384, and 415 g/d, weaning weight 24.92, 26.18, and 28.07 kg, as well as lactobacilli population 5.79, 6.32, and $6.48Log_{10}cfu/g$, for T1, T2, and T3, respectively. Lambs fed L. casei had decreased ($p{\leq}0.05$) populations of total coliforms (T1 = 6.18, T2 = 5.77, and $T3=5.07Log_{10}cfu/g$), diarrheas incidence (T1 = 11.67%, T2 = 8.33%, and T3 = 5.0%), and serum cholesterol concentration (11% in T2 and 13% in T3, compared to control). Conclusion: The combination of Agave tequilana inulin and L. casei increases weight gain and improves intestinal health by reducing coliforms and diarrheas incidence in $Katahdin{\times}Dorset$ lambs during the pre-weaning period.