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Frontiers in Cellular and Infection... 2024Numerous studies have demonstrated the influence of gut microbiota on the development of obesity. In this study, we utilized Mendelian randomization (MR) analysis to...
BACKGROUND
Numerous studies have demonstrated the influence of gut microbiota on the development of obesity. In this study, we utilized Mendelian randomization (MR) analysis to investigate the gut microbiota characteristics among different types of obese patients, aiming to elucidate the underlying mechanisms and provide novel insights for obesity treatment.
METHODS
Two-sample multivariable Mendelian randomization (MR) analysis was employed to assess causal relationships between gut microbiota and various obesity subtypes. Gut microbiota data were obtained from the international consortium MiBioGen, and data on obese individuals were sourced from the Finnish National Biobank FinnGen. Eligible single-nucleotide polymorphisms (SNPs) were selected as instrumental variables. Various analytical methods, including inverse variance weighted (IVW), MR-Egger regression, weighted median, MR-RAPS, and Lasso regression, were applied. Sensitivity analyses for quality control included MR-Egger intercept tests, Cochran's Q tests, and leave-one-out analyses and others.
RESULTS
Mendelian randomization studies revealed distinct gut microbiota profiles among European populations with different obesity subtypes. Following multivariable MR analysis, we found that [: 0.842, : 0.766-0.926, Adjusted value: 0.028] independently reduced the risk of obesity induced by excessive calorie intake, while [: 4.252, : 2.177-8.307, Adjusted value: 0.002] independently increased the risk of medication-induced obesity. For localized adiposity, [: 0.213, : 0.115-0.395, Adjusted value: <0.001] acted as a protective factor. In the case of extreme obesity with alveolar hypoventilation, [: 0.724, : 0.609-0.860, Adjusted value: 0.035] reduced the risk of its occurrence. Additionally, six gut microbiota may have potential roles in the onset of different types of obesity. Specifically, the torques group may increase the risk of its occurrence. and may serve as protective factors in the onset of Drug-induced obesity. , , and , on the other hand, could potentially increase the risk of Drug-induced obesity. No evidence of heterogeneity or horizontal pleiotropy among SNPs was found in the above studies (all values for Q test and MR-Egger intercept > 0.05).
CONCLUSION
Gut microbiota abundance is causally related to obesity, with distinct gut microbiota profiles observed among different obesity subtypes. Four bacterial species, including , , and independently influence the development of various types of obesity. Probiotic and prebiotic supplementation may represent a novel approach in future obesity management.
Topics: Humans; Gastrointestinal Microbiome; Obesity; Actinomycetaceae; Bacteroidetes; Clostridiales; Lactobacillus; Nonoxynol; Genome-Wide Association Study
PubMed: 38375360
DOI: 10.3389/fcimb.2024.1352109 -
Chinese Herbal Medicines Jan 2024The mild-natured and bitter-flavored traditional Chinese medicines (MB-TCMs) are an important class of TCMs that have been widely used in clinical practice and... (Review)
Review
The mild-natured and bitter-flavored traditional Chinese medicines (MB-TCMs) are an important class of TCMs that have been widely used in clinical practice and recognized as safe long-term treatments for chronic diseases. However, as an important class of TCMs, the panorama of pharmacological effects and the mechanisms of MB-TCMs have not been systemically reviewed. Compelling studies have shown that gut microbiota can mediate the therapeutic activity of TCMs and help to elucidate the core principles of TCM medicinal theory. In this systematic review, we found that MB-TCMs commonly participated in the modulation of metabolic syndrome, intestinal inflammation, nervous system disease and cardiovascular system disease in association with promoting the growth of beneficial bacteria , , , , as well as inhibiting the proliferation of harmful bacteria , , and . These alterations, correspondingly, enhance the generation of protective metabolites, mainly including short-chain fatty acids (SCFAs), bile acid (BAs), 5-hydroxytryptamine (5-HT), indole and gamma-aminobutyric acid (GABA), and inhibit the generation of harmful metabolites, such as proinflammatory factors trimethylamine oxide (TAMO) and lipopolysaccharide (LPS), to further exert multiplicative effects for the maintenance of human health through several different signaling pathways. Altogether, this present review has attempted to comprehensively summarize the relationship between MB-TCMs and gut microbiota by establishing the TCMs-gut microbiota-metabolite-signaling pathway-diseases axis, which may provide new insight into the study of TCM medicinal theories and their clinical applications.
PubMed: 38375054
DOI: 10.1016/j.chmed.2023.08.001 -
PloS One 2024Sanhua decoction (SHD), a traditional prescription, has long been used in treating ischemic stroke (IS). However, the therapeutic effect of SHD and the associated...
Sanhua decoction (SHD), a traditional prescription, has long been used in treating ischemic stroke (IS). However, the therapeutic effect of SHD and the associated changes in gut microbiota and short-chain fatty acids (SCFAs) are uncertain. In this study, a rat model of IS was established by the middle cerebral artery occlusion (MCAO). By evaluating the cerebral infarct area and brain tissue pathology, it was found that SHD ameliorated IS-related symptoms in MCAO rats. Using 16S rRNA gene sequencing, we found that SHD reduced abnormally elevated Lactobacillus and opportunistic pathogens such as Desulfovibrio, but increased some beneficial bacteria that produce SCFAs, including Clostridia, Lachnospiraceae, Ruminococcaceae, and Coprococcus. KEGG analysis revealed that SHD regulates several pathways, including D-arginine and D-ornithine metabolism, polyketide sugar unit biosynthesis, and cyanoamino acid metabolism, which are significantly altered in MCAO rats. By gas chromatography-mass spectrometry detection of SCFAs, we found that fecal acetic acid, valeric acid, and caproic acid were significantly increased in MCAO rats, whereas propionic acid and isobutyric acid were decreased. SHD reversed the changes in acetic acid and propionic acid in the model rats and significantly increased fecal butyric acid. In addition, MCAO rats had significantly higher serum levels of acetic acid, butyric acid, isovaleric acid, and valeric acid, and lower levels of caproic acid. Altered serum levels of butyric acid, isovaleric acid, valeric acid, and caproic acid were restored, and the level of isobutyric acid was reduced after SHD administration. Spearman analysis revealed that cerebral infarct area had a strong correlation with Bifidobacterium, Desulfovibrio, Lachnospiraceae, Lactobacillus, acetic acid, valeric acid, and caproic acid. Overall, this study demonstrates for the first time that the effect of SHD on IS may be related to gut microbiota and SCFAs, providing a potential scientific explanation for the ameliorative effect of SHD on IS.
Topics: Rats; Animals; Propionates; Caproates; Gastrointestinal Microbiome; Isobutyrates; Infarction, Middle Cerebral Artery; RNA, Ribosomal, 16S; Fatty Acids, Volatile; Acetic Acid; Butyric Acid; Pentanoic Acids; Hemiterpenes
PubMed: 38363776
DOI: 10.1371/journal.pone.0298148 -
Animal Nutrition (Zhongguo Xu Mu Shou... Mar 2024This study was conducted to explore the regulatory mechanism of leucine (Leu) on lipid metabolism of finishing pigs. Twenty-four Duroc × Landrace × Large cross...
This study was conducted to explore the regulatory mechanism of leucine (Leu) on lipid metabolism of finishing pigs. Twenty-four Duroc × Landrace × Large cross pigs with an average body weight of 68.33 ± 0.97 kg were randomly allocated into 3 treatment groups with 8 replicates per group (1 pig per replicate). The dietary treatments were as follows: control group (CON), 0.25% Leu group and 0.50% Leu group. The experimental period was 42 d. The results showed as follows. (1) Compared with the CON, 0.25% and 0.50% Leu increased ( < 0.01) the average daily gain (ADG), while the average backfat thickness (ABT) and the ratio of feed intake to body weight gain (F:G ratio) were decreased ( < 0.05). (2) In the 0.25% Leu group, the relative mRNA expression levels of sterol regulatory element binding protein-1c (), recombinant fatty acid transport protein 1 (), chemerin and peroxisome proliferator-activated receptor γ () were decreased but the level of fatty acid binding protein 4 () and fatty acid translocase () were increased in backfat tissue. In the 0.25% Leu group, the protein levels of p-Rictor, p-Raptor, p-eIF4E-binding protein 1 (p-4EBP1), p-silent mating type information regulator 2 homolog 1 (p-SIRT1) and acetylation ribosome s6 protein kinase 1 (Ac-S6K1) were increased ( < 0.05). (3) Compared to the CON, the diversity of gut microbiota in the 0.25% Leu group was increased. Principal component analysis showed that the relative abundance of Bacteroidetes, and was higher in the 0.25% Leu group than the CON, but the relative abundance of Firmicutes, and was lower than in the CON ( < 0.05). (4) Four different metabolites were screened out from the serum of finishing pigs including allolithocholic acid (alloLCA), isolithocholic acid (isoLCA), ursodeoxycholic acid (UDCA) and hyodeoxycholic acid (HDCA), which correlate to various degrees with the above microorganisms. In conclusion, Leu could promote adipose tissue lipolysis of finishing pigs through the mTOR-SIRT1 signaling pathway, and S6K1 is acetylated at the same time, and the interaction between gut microbiota and bile acid metabolism is also involved.
PubMed: 38357569
DOI: 10.1016/j.aninu.2023.10.005 -
Neuropsychiatric Disease and Treatment 2024The diversity and composition of the oral and gut microbiota of depressed rats were analyzed to explore the microbiological etiology of major depressive disorder (MDD).
PURPOSE
The diversity and composition of the oral and gut microbiota of depressed rats were analyzed to explore the microbiological etiology of major depressive disorder (MDD).
METHODS
The depressed rat model was established by inducing chronic unpredictable mild stress (CUMS). After the establishment of the model, body weight measurements and behavioral tests were conducted. The diversity and composition of oral and gut microbiota were analyzed using 16SrRNA sequencing.
RESULTS
There were significant differences in the alpha and beta diversity of the oral microbiota of rats in the CUMS and control groups. The top three most abundant genera in the oral microbiota were , , and . Linear discriminant analysis effect size (LEfSe) analysis showed that the abundance of decreased and that of Psychrotrophs increased in the CUMS group, and the differences were statistically significant. The top three most abundant genera in the gut microbiota were and . LEfSe analysis showed that the abundance of decreased in the CUMS group, and the difference was statistically significant. Spearman correlation analysis was performed to analyze the differential microbiota and depression-like behavior, which showed that differential microbiota significantly correlated with body weight, total distance traveled, average speed, and number of rearing. Spearman correlation analysis of oral and gut differential microbiota demonstrated a strong positive correlation between in the oral cavity and in the intestine (=0.64-0.73, <0.01); along with a strong negative correlation between in the oral cavity and , in the intestine(=-0.51--0.72, <0.05).
CONCLUSION
Significant differences were observed in the diversity and composition of oral and gut microbiota between the CUMS depression model and control groups. Modulating the oral and gut microbiota may have positive effects on MDD.
PubMed: 38344423
DOI: 10.2147/NDT.S448940 -
Journal of Translational Medicine Feb 2024Overweight is known to be an important risk factor for colorectal cancer (CRC), and the differences in intestinal flora among CRC patients with different BMI status have...
BACKGROUND
Overweight is known to be an important risk factor for colorectal cancer (CRC), and the differences in intestinal flora among CRC patients with different BMI status have not been clearly defined. The purpose of this study was to elucidate the differences in the abundance, composition and biological function of intestinal flora in CRC patients with different BMI status.
METHOD
A total of 170 CRC patients were included and grouped according to the BMI data of CRC patients. BMI ≥ 24 kg/m was defined as overweight group, and BMI within the range of 18.5-23.9 kg/m was defined as normal weight group. Preoperative stool collection of patients in both groups was used for 16S rRNA sequencing. Total RNA was extracted from 17 CRC tumor tissue samples for transcriptome sequencing, and then CIBERSORT algorithm was used to convert the transcriptome data into the relative content matrix of 22 kinds of immune cells, and the correlation between different intestinal flora and immune cells and immune-related genes under different BMI states was analyzed. Finally, we identified BMI-related differential functional pathways and analyzed the correlation between these pathways and differential intestinal flora.
RESULT
There was no significant difference in α diversity and β diversity analysis between overweight group and normal weight group. Partial least square discriminant analysis (PLS-DA) could divide the flora into two different clusters according to BMI stratification. A total of 33 BMI-related differential flora were identified by linear discriminant effect size analysis (LEfSe), among which Actinomyces, Desulfovibrio and Bacteroides were significantly enriched in overweight group. ko00514: Other types of O-glycan biosynthesis are significantly enriched in overweight group. There was a significant positive correlation between Clostridium IV and Macrophages M2 and T cells regulatory (Tregs). There was a significant negative correlation with Dendritic cells activated and T cells CD4 memory activated.
CONCLUSIONS
The richness and diversity of intestinal flora of CRC patients may be related to different BMI status, and the enrichment of Actinomyces, Desulphurvibrio and Bacteroides may be related to overweight status of CRC patients. The tumor microenvironment in which BMI-related differential flora resides has different immune landscapes, suggesting that some intestinal flora may affect the biological process of CRC by regulating immune cell infiltration and immune gene expression, but further experiments are needed to confirm this.
Topics: Humans; Gastrointestinal Microbiome; Body Mass Index; RNA, Ribosomal, 16S; Overweight; Colorectal Neoplasms; Tumor Microenvironment
PubMed: 38331839
DOI: 10.1186/s12967-024-04903-7 -
Frontiers in Microbiology 2024The primary objective of the current study was to evaluate the effects of mushroom residue (FVMR) in a fermented total mixed ration (FTMR) diet on the fattening effect...
INTRODUCTION
The primary objective of the current study was to evaluate the effects of mushroom residue (FVMR) in a fermented total mixed ration (FTMR) diet on the fattening effect and rumen microorganisms in Guizhou black male goats.
METHODS
A total of 22 Guizhou black male goats were allocated into two groups using the Randomized Complete Block Design (RCBD) experimental design. The average initial weight was 22.41 ± 0.90 kg and with 11 goats in each group. The control group (group I) was fed the traditional fermentation total mixed ration (FTMR) diet without FVMR. Group II was fed the 30% FVMR in the FTMR diet.
RESULTS
The results showed that compared with group I, the addition of FVMR in the goat diet could reduce the feed cost and feed conversion ratio (FCR) of group II ( < 0.01). Notably, the apparent digestibility of crude protein (CP), acid detergent fiber (ADF), neutral detergent fiber (NDF), and dry matter (DM) were higher in group II ( < 0.01). The levels of growth hormone (GH), immunoglobulin A (IgA), and immunoglobulin M (IgM) in group II were higher than that of group I ( < 0.01), which the level of glutamic oxalacetic transaminase (ALT) and interleukin-6 (IL-6) was noticeably lower than that of group I ( < 0.01). 30% FVMR in FTMR diets had no effect on rumen fermentation parameters and microbial composition at the phylum level of Guizhou black male goats ( > 0.05). However, at the genus level, the relative abundance of , and in group II was lower than in group I ( < 0.05), and the relative abundance of was higher than in group I ( < 0.01).
DISCUSSION
In conclusion, the results of the current study indicated that 30% FVMR in the FTMR diet improves rumen fermentation and rumen microbial composition in Guizhou black male goats, which improves growth performance, apparent digestibility, and immunity.
PubMed: 38328420
DOI: 10.3389/fmicb.2024.1347853 -
BMC Psychiatry Jan 2024Major depressive disorder (MDD) is characterized by sadness and anhedonia, but also physical symptoms such as changes in appetite and weight. Gut microbiota has been...
BACKGROUND
Major depressive disorder (MDD) is characterized by sadness and anhedonia, but also physical symptoms such as changes in appetite and weight. Gut microbiota has been hypothesized to be involved in MDD through gut-brain axis signaling. Moreover, antidepressants display antibacterial properties in the gastrointestinal tract. The aim of this study was to compare the gut microbiota and systemic inflammatory profile of young patients with MDD before and after initiation of antidepressant treatment and/or psychotherapy in comparison with a non-depressed control group (nonMDD).
METHODS
Fecal and blood samples were collected at baseline and at follow-up after four and twelve weeks, respectively. Patients started treatment immediately after collection of the baseline samples. The gut microbiota was characterized by 16 S rRNA gene sequencing targeting the hypervariable V4 region. Plasma levels of 49 unique immune markers were assessed using Mesoscale.
RESULTS
In total, 27 MDD patients and 32 nonMDD controls were included in the study. The gut microbiota in the baseline samples of MDD versus nonMDD participants did not differ regarding α- or β-diversity. However, there was a higher relative abundance of the genera Ruminococcus gnavus group, and a lower relative abundance of the genera Desulfovibrio, Tyzzerella, Megamonas, Olsenella, Gordonibacter, Allisonella and Rothia in the MDD group compared to the nonMDD group. In the MDD group, there was an increase in the genera Rothia, Desulfovibrio, Gordinobacteer and Lactobacillus, while genera belonging to the Firmicutes phylum were found depleted at twelve weeks follow-up compared to baseline. In the MDD group, IL-7, IL-8 and IL-17b levels were elevated compared to the nonMDD group at baseline. Furthermore, MDI score in the MDD group was found to correlate with Bray-Curtis dissimilarity at baseline, and several inflammatory markers at both baseline and after initiation of antidepressant treatment.
CONCLUSION
Several bacterial taxa differed between the MDD group and the nonMDD group at baseline and changed in relative abundance during antidepressant treatment and/or psychotherapy. The MDD group was furthermore found to have a pro-inflammatory profile compared to the nonMDD group at baseline. Further studies are required to investigate the gut microbiota and pro-inflammatory profile of patients with MDD.
Topics: Humans; Depressive Disorder, Major; Gastrointestinal Microbiome; Antidepressive Agents; Cognition; Psychotherapy
PubMed: 38297265
DOI: 10.1186/s12888-024-05547-z -
Biomedicine & Pharmacotherapy =... Dec 2023The high risk for anxiety and depression among individuals with stress has become a growing concern globally. Stress-related mental disorders are often accompanied by...
The high risk for anxiety and depression among individuals with stress has become a growing concern globally. Stress-related mental disorders are often accompanied by symptoms of metabolic dysfunction. Cordycepin is a Chinese herbal medicine commonly used for its metabolism-enhancing effects. We aimed to investigate the dose-dependent effects of cordycepin on psycho-metabolic disorders induced by stress. Our behavioral tests revealed that 12.5 mg/kg cordycepin by oral gavage significantly attenuated the anxiety- and depression-like behaviors induced by stress in mice. At 25 mg/kg, cordycepin restored the reduced weight and cell size of adipose tissues caused by stress. Besides ameliorating the metabolic dysbiosis of gut microbiota due to stress, cordycepin significantly reduced the elevated contents of 5-hydroxyindoleacetic acid in the serum and prefrontal cortex at 12.5 mg/kg and reversed the decrease in adipose induced by stress at 25 mg/kg. Correlation analyses further revealed that 12.5 mg/kg cordycepin reversed stress-induced changes in the intestinal microbiome of NK4A214_group and decreased serum Myristic acid and PC(15:0/18:1(11Z)) and cytokines, such as IFN-γ and IL-1β. 25 mg/kg cordycepin reversed stress-induced changes in the abundances of Prevoteaceae_UCG-001 and Desulfovibrio, increased serum L-alanine level, and decreased serum Inosine-5'-monophosphate level. Cordycepin thereby ameliorated the anxiety- and depression-like behaviors as well as disturbances in the adipose metabolism of mice exposed to stress. Overall, these findings offer evidence indicating that the prominent effects of cordycepin in the brain and adipose tissues are dose dependent, thus highlight the importance of evaluating the precise therapeutic effects of different cordycepin doses on psycho-metabolic diseases.
Topics: Humans; Mice; Animals; Gastrointestinal Microbiome; Obesity; Brain; Deoxyadenosines; Depression
PubMed: 38294969
DOI: 10.1016/j.biopha.2023.115796 -
Frontiers in Microbiology 2023Colorectal cancer (CRC) commonly arises in individuals with premalignant colon lesions known as polyps, with both conditions being influenced by gut microbiota....
Colorectal cancer (CRC) commonly arises in individuals with premalignant colon lesions known as polyps, with both conditions being influenced by gut microbiota. Host-related factors and inherent characteristics of polyps and tumors may contribute to microbiome variability, potentially acting as confounding factors in the discovery of taxonomic biomarkers for both conditions. In this study we employed shotgun metagenomics to analyze the taxonomic diversity of bacteria present in fecal samples of 90 clinical subjects (comprising 30 CRC patients, 30 with polyps and 30 controls). Our findings revealed a decrease in taxonomic richness among individuals with polyps and CRC, with significant dissimilarities observed among the study groups. We identified significant alterations in the abundance of specific taxa associated with polyps (Streptococcaceae, , and ) and CRC (Lactobacillales, Clostridiaceae, , SFB, , and ). Clostridiaceae exhibited significantly lower abundance in the early stages of CRC. Additionally, our study revealed a positive co-occurrence among underrepresented genera in CRC, while demonstrating a negative co-occurrence between and , suggesting potential antagonistic relationships. Moreover, we observed variations in taxonomic richness and/or abundance within the polyp and CRC bacteriome linked to polyp size, tumor stage, dyslipidemia, diabetes with metformin use, sex, age, and family history of CRC. These findings provide potential new biomarkers to enhance early CRC diagnosis while also demonstrating how intrinsic host factors contribute to establishing a heterogeneous microbiome in patients with CRC and polyps.
PubMed: 38293554
DOI: 10.3389/fmicb.2023.1292490