Dysbiosis of Gut Microbiome Aggravated Male Infertility in Captivity of Plateau Pika.

Captivity is an important and efficient technique for rescuing endangered species. However, it induces infertility, and the underlying mechanism remains obscure. This study used the plateau pika (Ochotona curzoniae) as a model to integrate physiological, metagenomic, metabolomic, and transcriptome analyses and explore whether dysbiosis of the gut microbiota induced by artificial food exacerbates infertility in captive wild animals. Results revealed that captivity significantly decreased testosterone levels and the testicle weight/body weight ratio. RNA sequencing revealed abnormal gene expression profiles in the testicles of captive animals. The microbial α-diversity and Firmicutes/Bacteroidetes ratio were drastically decreased in the captivity group. Bacteroidetes and Muribaculaceae abundance notably increased in captive pikas. Metagenomic analysis revealed that the alteration of flora increased the capacity for carbohydrate degradation in captivity. The levels of microbe metabolites' short-chain fatty acids (SCFAs) were significantly high in the captive group. Increasing SCFAs influenced the immune response of captivity plateau pikas; pro-inflammatory cytokines were upregulated in captivity. The inflammation ultimately contributed to male infertility. In addition, a positive correlation was observed between Gastranaerophilales family abundance and testosterone concentration. Our results provide evidence for the interactions between artificial food, the gut microbiota, and male infertility in pikas and benefit the application of gut microbiota interference in threatened and endangered species.

Repeated antibiotic drug treatment negatively affects memory function and glutamatergic nervous system of the hippocampus in mice.

The gut microbiota is associated with memory; however, the relationship between dysbiosis-induced memory deficits and hippocampal glutamatergic neurons remains unclear. In our study, a mouse dysbiosis model showed impaired memory-related behavior in the passive avoidance test; decreased expression levels of glutaminase, excitatory amino acid transporter (EAAT)1, EAAT2, vesicular glutamate transporter 2, synaptophysin, brain-derived neurotrophic factor, doublecortin, neuronal nuclear protein, glial fibrillary acidic protein, and S100ß; and decreased phosphorylation of N-methyl-D-aspartate receptor subunit 1, calmodulin-dependent protein kinase II, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit 1, and cAMP response element-binding protein in the hippocampus. This suggests that dysbiosis-induced memory dysfunction is associated with the hippocampal glutamatergic nervous system.

Psychobiotics Lactiplantibacillus plantarum JYLP-326: Antidepressant-like effects on CUMS-induced depressed mouse model and alleviation of gut microbiota dysbiosis.

BACKGROUND: Depression affects a significant portion of the global population and has emerged as one of the most debilitating conditions worldwide. Recent studies have explored the relationship between depression and the microbiota of the intestine, revealing potential avenues for effective treatment. METHODS: To evaluate the potential alleviation of depression symptoms, we employed a depression C57BL/6 mice model induced by chronic unpredictable mild stress (CUMS). We administered Lactiplantibacillus plantarum JYLP-326 and conducted various animal behavior tests, including the open-field test (OFT), sucrose preference test (SPT), and tail-suspension test (TST). Additionally, we conducted immunohistochemistry staining and analyzed the hippocampal and colon parts of the mice. RESULTS: The results of the behavior tests indicated that L. plantarum JYLP-326 alleviated spontaneous behavior associated with depression. Moreover, the treatment led to significant improvements in GFAP and Iba1, suggesting its potential neuroprotective effects. Analysis of the hippocampal region indicated that L. plantarum JYLP-326 administration upregulated p-TPH2, TPH2, and 5-HT1AR, while downregulating the expression of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. In the colon, the treatment inhibited the TLR4-MyD88-NF-κB pathway and increased the levels of occludin and ZO-1, indicating improved intestinal barrier function. Additionally, the probiotic demonstrated a regulatory effect on the HMGB1-RAGE-TLR4 signaling pathway. CONCLUSIONS: Our findings demonstrate that L. plantarum JYLP-326 exhibits significant antidepressant-like effects in mice, suggesting its potential as a therapeutic approach for depression through the modulation of gut microbiota. However, further investigations and clinical trials are required to validate its safety and efficacy for human use.

Protective Mechanism of Polysaccharide ORP-1 Isolated from Oudemansiella raphanipes against Age-Related Cognitive Decline through the Microbiota-Gut-Brain Axis.

Age-related cognitive decline is primarily attributed to the progressive weakening of synaptic function and loss of synapses, while age-related gut microbial dysbiosis is known to impair synaptic plasticity and cognitive behavior by metabolic alterations. To improve the health of the elderly, the protective mechanisms of Oudemansiella raphanipes polysaccharide (ORP-1) against age-related cognitive decline are investigated. The results demonstrate that ORP-1 and its gut microbiota-derived metabolites SCFAs restore a healthy gut microbial population to handle age-related gut microbiota dysbiosis mainly by increasing the abundance of beneficial bacteria Dubosiella, Clostridiales, and Prevotellaceae and reducing the abundance of harmful bacteria Desulfovibrio, strengthen intestinal barrier integrity by abolishing age-related alterations of tight junction (TJ) and mucin 2 (MUC2) proteins expression, diminish age-dependent increase in circulating inflammatory factors, ameliorate cognitive decline by reversing memory- and synaptic plasticity-related proteins levels, and restrain hyperactivation of microglia-mediated synapse engulfment and neuroinflammation. These findings expand the understanding of prebiotic-microbiota-host interactions.

High fat diet is associated with gut microbiota dysbiosis and decreased gut microbial derived metabolites related to metabolic health in young Göttingen Minipigs.

The objectives were 1) to characterize a Göttingen Minipig model of metabolic syndrome regarding its colon microbiota and circulating microbial products, and 2) to assess whether ovariectomized female and castrated male minipigs show similar phenotypes. Twenty-four nine-week-old Göttingen Minipigs were allocated to four groups based on sex and diet: ovariectomized females and castrated males fed either chow or high-fat diet (HFD) for 12 weeks. At study end, body composition and plasma biomarkers were measured, and a mixed meal tolerance test (MMT) and an intravenous glucose tolerance test (IVGTT) were performed. The HFD groups had significantly higher weight gain, fat percentage, fasting plasma insulin and glucagon compared to the chow groups. Homeostatic model assessment of insulin resistance index (HOMA-IR) was increased and glucose effectiveness derived from the IVGTT and Matsuda´s insulin sensitivity index from the MMT were decreased in the HFD groups. The HFD groups displayed dyslipidemia, with significantly increased total-, LDL- and HDL-cholesterol, and decreased HDL/non-HDL cholesterol ratio. The colon microbiota of HFD minipigs clearly differed from the lean controls (GuniFrac distance matrix). The main bacteria families driving this separation were Clostridiaceae, Fibrobacteraceae, Flavobacteriaceae and Porphyromonadaceae. Moreover, the species richness was significantly decreased by HFD. In addition, HFD decreased the circulating level of short chain fatty acids and beneficial microbial metabolites hippuric acid, xanthine and trigonelline, while increasing the level of branched chain amino acids. Six and nine metabolically relevant genes were differentially expressed between chow-fed and HFD-fed animals in liver and omental adipose tissue, respectively. The HFD-fed pigs presented with metabolic syndrome, gut microbial dysbiosis and a marked decrease in healthy gut microbial products and thus displayed marked parallels to human obesity and insulin resistance. HFD-fed Göttingen Minipig therefore represents a relevant animal model for studying host-microbiota interactions. No significant differences between the castrated and ovariectomized minipigs were observed.

Dysbiosis of gut microbiota and metabolites is associated with radiation-induced colorectal fibrosis and is restored by adipose-derived mesenchymal stem cell therapy.

AIMS: This study aimed to investigate the effects of adipose-derived mesenchymal stem cells (ADSCs) on radiation-induced colorectal fibrosis (RICF) along with the associated dysbiosis of gut microbiota and metabolites. MAIN METHODS: Fecal microbiota were assessed through 16S rRNA gene sequencing, and the fecal metabolome was characterized using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. The correlation between microbiota and metabolome data was explored. KEY FINDINGS: ADSC injection demonstrated a significant restoration of radiation-induced intestinal damage in vivo. At the phylum level, irradiated rats exhibited an increase in Bacteroidota and Campilobacterota, and a decrease in Firmicutes and Desulfobacterota, contrasting with the ADSC treatment group. Metabolomic analysis revealed 72 differently expressed metabolites (DEMs) from gas chromatography-mass spectrometry and 284 DEMs from liquid chromatography-mass spectrometry in the radiation group compared to the blank group. In the ADSC treatment group versus the radiation group, 36 DEMs from gas chromatography-mass spectrometry and 341 DEMs from liquid chromatography-mass spectrometry were identified. KEGG enrichment analysis implicated pathways such as steroid hormone biosynthesis, gap junction, primary bile acid biosynthesis, citrate cycle, cAMP signaling pathway, and alanine, aspartate, and glutamate metabolism during RICF progression and after treated with ADSCs. Correlation analysis highlighted the role of ADSCs in modulating the metabolic process of Camelledionol in fecal Bacteroides. SIGNIFICANCE: These findings underscore the potential of ADSCs in reversing dysbiosis and restoring normal colonic flora in the context of RICF, offering valuable insights for therapeutic interventions targeting radiation-induced complications.

Semaglutide alleviates gut microbiota dysbiosis induced by a high-fat diet.

This study investigated the effects of semaglutide (Sema) on the gut microbiota of obese mice induced with high-fat diet (HFD). Male C57BL/6 J mice aged 6 weeks were enrolled and randomly distributed to four groups, which were provided with a normal control diet (NCD,NCD + Sema) and a 60% proportion of a high-fat diet (HFD,HFD + Sema), respectively. HFD was given for 10 weeks to develop an obesity model and the intervention was lasted for 18 days. The results showed semaglutide significantly reduced body weight gain, areas under the curve (AUC) of glucose tolerance test and insulin resistance test, as well as adipose tissue weight in mice. Semaglutide effectively reduced lipid deposition and lipid droplet formation in the liver of obese mice, and regulated the expression of genes related to abnormal blood glucose regulation. Additionally, semaglutide influenced the composition of gut microbiota, mitigating the microbial dysbiosis induced by a high-fat diet by impacting the diversity of the gut microbiota. After the high-fat diet intervention, certain strains such as Akkermansia, Faecalibaculum, and Allobaculum were significantly decreased, while Lachnospiraceae and Bacteroides were significantly increased. However, the application of semaglutide restored the lost flora and suppressed excessive bacterial abundance. Moreover, semaglutide increased the content of tight junction proteins and repaired the damage to intestinal barrier function caused by the high-fat diet intervention. Furthermore, correlation analysis revealed inverse relationship among Akkermansia levels and weight gain, blood glucose levels, and various obesity indicators. Correlation analysis also showed that Akkermansia level was negatively correlated with weight gain, blood glucose levels and a range of obesity indicators. This phenomenon may explain the anti-obesity effect of semaglutide, which is linked to alterations in gut microbiota, specifically an increase in the abundance of Akkermansia. In summary, our findings indicate that semaglutide has the potential to alleviate gut microbiota dysbiosis, and the gut microbiota may contribute to the obesity-related effects of this drug.

Limonin alleviates high-fat diet-induced dyslipidemia by regulating the intestinal barrier via the microbiota-related ILC3-IL22-IL22R pathway.

High-fat diet (HFD)-induced dyslipidemia is frequently accompanied by gut microbiota dysbiosis and a compromised gut barrier. Enhancing the intestinal barrier function emerges as a potential therapeutic approach for dyslipidemia. The ILC3-IL22-IL22R pathway, which responds to dietary and microbial signals, has not only attracted attention for its crucial role in maintaining the intestinal barrier, but recent reports have also suggested its potential in regulating lipid metabolism. Limonin is derived from the Chinese herb Evodiae fructus, which has shown potential in ameliorating dysbiosis of serum lipids. However, its underlying mechanisms remain elusive. Consequently, targeting the ILC3-IL22-IL22R pathway to enhance intestinal barrier function holds promise as a therapeutic approach for dyslipidemia. In this study, male C57BL/6 mice were subjected to a 16-week HFD to induce dyslipidemia and concurrently administered oral limonin. We discovered that limonin supplementation dramatically reduced serum lipid profiles in HFD-fed mice, significantly curbing HFD-induced weight gain and epididymal fat accumulation. Ileal histopathological evaluation indicated limonin's ameliorative effects on HFD-induced intestinal barrier impairment. Limonin also moderated the intestinal microbiota dysbiosis, which is characterized by the elevation of Firmicutes in HFD mice, and notably amplified the abundance of probiotic Lactobacillus. In addition, supported by flow cytometry and other analyses, we observed that limonin upregulated the ILC3-IL22-IL22R pathway, enhancing phosphorylated STAT3 (pSTAT3) in intestinal epithelial cells (IECs), thereby reducing lipid transporter expression. In conclusion, our study revealed that limonin exerted a promising preventive effect against HFD-induced dyslipidemia by the mitigation of the intestinal barrier function and intestinal microbiota, and its mechanism was related to the upregulation of the ILC3-IL22-IL22R pathway.

Claudin-2 upregulation enhances intestinal permeability, immune activation, dysbiosis, and mortality in sepsis.

Intestinal epithelial expression of the tight junction protein claudin-2, which forms paracellular cation and water channels, is precisely regulated during development and in disease. Here, we show that small intestinal epithelial claudin-2 expression is selectively upregulated in septic patients. Similar changes occurred in septic mice, where claudin-2 upregulation coincided with increased flux across the paracellular pore pathway. In order to define the significance of these changes, sepsis was induced in claudin-2 knockout (KO) and wild-type (WT) mice. Sepsis-induced increases in pore pathway permeability were prevented by claudin-2 KO. Moreover, claudin-2 deletion reduced interleukin-17 production and T cell activation and limited intestinal damage. These effects were associated with reduced numbers of neutrophils, macrophages, dendritic cells, and bacteria within the peritoneal fluid of septic claudin-2 KO mice. Most strikingly, claudin-2 deletion dramatically enhanced survival in sepsis. Finally, the microbial changes induced by sepsis were less pathogenic in claudin-2 KO mice as survival of healthy WT mice injected with cecal slurry collected from WT mice 24 h after sepsis was far worse than that of healthy WT mice injected with cecal slurry collected from claudin-2 KO mice 24 h after sepsis. Claudin-2 upregulation and increased pore pathway permeability are, therefore, key intermediates that contribute to development of dysbiosis, intestinal damage, inflammation, ineffective pathogen control, and increased mortality in sepsis. The striking impact of claudin-2 deletion on progression of the lethal cascade activated during sepsis suggests that claudin-2 may be an attractive therapeutic target in septic patients.

Ethanol extracts of Isochrysis zhanjiangensis alleviate acute alcoholic liver injury and modulate intestinal bacteria dysbiosis in mice.

BACKGROUND: Alcoholic liver disease (ALD) is responsible for 3.3 million deaths per annum. Efficacious therapeutic modalities or drug treatments for ALD have not yet been found, so it is urgent to seek new agents for preventing ALD and its related disease. Many experiments have indicated that modulating the gut microbiota and regulating the toll-like receptor 4 (TLR4)/nuclear transcription factor-κB (NF-κB) inflammatory pathway can provide a new target for prevention and treatment of ALD. Marine microalgae have their natural metabolic pathways to synthesize various of bioactive compounds as promising candidates for hepatoprotection. In this study, we investigated ethanol extracts from Isochrysis zhanjiangensis (EEIZ) to evaluate their ability to alleviate acute alcoholic liver injury, regulate TLR4/NF-κB inflammatory pathway and modulate intestinal bacteria dysbiosis in mice for ALD treatment. RESULTS: In the acute ALD mouse model, EEIZ reduced levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triacylglyceride, total cholesterol and low-density lipoprotein, while increasing the level of high-density lipoprotein. Besides, TLR4, myeloid differentiation factor 88, NF-κB and tumor necrosis factor-α expression levels in liver tissue were effectively downregulated by EEIZ. Furthermore, treatment with EEIZ enhanced intestinal homeostasis and significantly alleviated the damage caused by alcohol. CONCLUSION: EEIZ showed effective hepatoprotective activity against alcohol-induced acute liver injury in mice as it could alleviate hepatocyte damage, suppress the TLR4/NF-κB inflammatory pathway and regulate the intestinal flora structure. EEIZ could be a good candidate for preventing acute alcoholic liver injury. © 2024 Society of Chemical Industry.

Correlation analysis of vaginal flora and immune function Th1/Th2 imbalance in women with high-risk HPV infections in the female reproductive tract.

The purpose of this study was to analyze the correlation between vaginal flora and immune function Type 1 helper T cells/Type 2 helper T cells imbalance in females having HPV infections at high risk within the female reproductive tract. We selected 150 female patients who visited our hospital for reproductive tract inflammation between March 2019 and March 2021. They were divided into high-risk HPV-positive and high-risk HPV-negative groups according to the results of the HPV tests. Vaginal flora composition, density, diversity, and Th1/Th2 immune cell cytokine expression were assessed, and their correlations were analyzed. Compared to the HPV-negative group at high risk, the HPV-positive group at high risk exhibited significantly higher rates of Lactobacillius abnormalities, Chlamydia trachomatis and Mycoplasma urealyticum positivity(P<0.05). However, no statistically significant differences in the rates of Neisseria gonorrhoeae, bacterial vaginosis, mould, and trichomonad positivity were observed in both groups (P>0.05). The high-risk HPV-positive group displayed significantly higher rates of abnormal vaginal flora density and diversity compared to the HPV-negative group at high risk (P < 0.05). Compared to the HPV-negative group at high risk, the HPV-positive group at high risk exhibited significantly lower expression levels of Th1, Th1/Th2, IFN-γ, and IL-2 and higher expression levels of Th2, IL-4, and IL-10(P<0.05). Among patients having HPV infections at high risk, those with abnormal vaginal flora had lower expression levels of Th1, Th1/Th2, IFN-γ, and IL-2 and higher expression levels of Th2, IL-4, and IL-10 compared to those with normal vaginal flora, all of which were statistically significant(P<0.05). Vaginal flora dysbiosis was correlated with Th1/Th2 imbalance (P<0.05). Women with high-risk HPV infections in the female reproductive tract exhibit abnormal vaginal flora and immune function Th1/Th2 imbalance, characterized by a shift from Th1 to Th2. Moreover, there is a close correlation between vaginal flora dysbiosis and immune function Th1/Th2 imbalance.

Gut microbiota contributes to bisphenol A-induced maternal intestinal and placental apoptosis, oxidative stress, and fetal growth restriction in pregnant ewe model by regulating gut-placental axis.

BACKGROUND: Bisphenol A (BPA) is an environmental contaminant with endocrine-disrupting properties that induce fetal growth restriction (FGR). Previous studies on pregnant ewes revealed that BPA exposure causes placental apoptosis and oxidative stress (OS) and decreases placental efficiency, consequently leading to FGR. Nonetheless, the response of gut microbiota to BPA exposure and its role in aggravating BPA-mediated apoptosis, autophagy, mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and OS of the maternal placenta and intestine are unclear in an ovine model of gestation. RESULTS: Two pregnant ewe groups (n = 8/group) were given either a subcutaneous (sc) injection of corn oil (CON group) or BPA (5 mg/kg/day) dissolved in corn oil (BPA group) once daily, from day 40 to day 110 of gestation. The maternal colonic digesta and the ileum and placental tissue samples were collected to measure the biomarkers of autophagy, apoptosis, mitochondrial dysfunction, ERS, and OS. To investigate the link between gut microbiota and the BPA-induced FGR in pregnant ewes, gut microbiota transplantation (GMT) was conducted in two pregnant mice groups (n = 10/group) from day 0 to day 18 of gestation after removing their intestinal microbiota by antibiotics. The results indicated that BPA aggravates apoptosis, ERS and autophagy, mitochondrial function injury of the placenta and ileum, and gut microbiota dysbiosis in pregnant ewes. GMT indicated that BPA-induced ERS, autophagy, and apoptosis in the ileum and placenta are attributed to gut microbiota dysbiosis resulting from BPA exposure. CONCLUSIONS: Our findings indicate the underlying role of gut microbiota dysbiosis and gut-placental axis behind the BPA-mediated maternal intestinal and placental apoptosis, OS, and FGR. The findings further provide novel insights into modulating the balance of gut microbiota through medication or probiotics, functioning via the gut-placental axis, to alleviate gut-derived placental impairment or FGR. Video Abstract.

Gut microbiota dysbiosis and intestinal barrier impairment in diarrhea caused by cold drink and high-fat diet.

Cold drink and high-fat diet (CDHFD) are common diet patterns. However, the potential risks remain unclear. We investigated the effects of CDHFD in adult mice and explored the mechanisms of action. Twenty adult male mice were randomly divided into control and model groups, and the control group was fed a normal diet, whereas the model group was fed CDHFD for 28 days. We found that mice in the model group developed diarrhea symptoms accompanied by fatigue and weakness. Analysis of the intestinal flora revealed that the model group had a lower diversity and richness of microorganism species in the gut than the control group. Furthermore, the characteristic analysis indicated that CDHFD downregulated specific bacteria, such as norank_f_Muribaculaceae, Muribaculum, and Odoribacter, which are known to be associated with the systemic inflammatory response and mucosal barrier function. Blood tests showed that immune cells and inflammatory cytokines were significantly elevated in the model group, along with increased LPS induced by CDHFD. Pathological investigations demonstrated that CDHFD damages the intestinal mucosa while affecting the expression of tight junction proteins, including ZO-1, Claudin-1, Claudin-2, and Occludin, which may be attributed to the activation of the TRAF6/IκB/p65 signaling pathway. In conclusion, impaired gut microbial and mechanical barrier function is responsible for CDHFD-induced diarrhea. In this study, we constructed a model of diet-induced diarrhea by simulating human dietary patterns, evaluated the long-term effects of CDHFD on human intestinal barriers and immune systems, and revealed its mechanism of action based on chronic inflammation. This study validated the model's fit to provide an effective screening model for drug or functional food development.

Dietary Restriction Improves Perioperative Neurocognitive Disorders by Inhibiting Neuroinflammation and Gut Microbial Dysbiosis.

Anesthesia/surgery have been identified as potential factors contributing to perioperative neurocognitive disorders, with a notably heightened risk observed in aging populations. One of the primary drivers of this impairment is believed to be neuroinflammation, specifically inflammation of hippocampal microglia. Dietary restriction has demonstrated a favorable impact on cognitive impairment across various disorders, primarily by quelling neuroinflammation. However, the precise influence of dietary restriction on perioperative neurocognitive disorders remains to be definitively ascertained. This investigation aims to explore the effects of dietary restriction on perioperative neurocognitive disorders and propose innovative therapeutic strategies for their management. The model of perioperative neurocognitive disorder was induced through exploratory laparotomy under isoflurane anesthesia. Cognitive performance was evaluated using the open field test, Barnes maze test, and fear conditioning test. The enzyme-linked immunosorbent assay (ELISA) was employed to quantify concentrations of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in both serum and hippocampal samples. The Western blot technique was utilized to assess expression levels of hippocampal PSD 95, Synaptophysin, TLR4, MyD88, and NF-kB p65. Microglial polarization was gauged using a combination of reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence labeling techniques. We conducted 16S rRNA sequencing to investigate the impact of dietary restriction on the intestinal flora of aged mice following anesthesia/surgery. Our findings indicate that dietary restrictions have the potential to ameliorate anesthesia/surgery-induced cognitive dysfunction. This effect is achieved through the modulation of gut microbiota, suppression of inflammatory responses in hippocampal microglia, and facilitation of neuronal repair and regeneration.

Potential effects of the most prescribed drugs on the microbiota-gut-brain-axis: A review.

The link between drug-induced dysbiosis and its influence on brain diseases through gut-residing bacteria and their metabolites, named the microbiota-gut-brain axis (MGBA), remains largely unexplored. This review investigates the effects of commonly prescribed drugs (metformin, statins, proton-pump-inhibitors, NSAIDs, and anti-depressants) on the gut microbiota, comparing the findings with altered bacterial populations in major brain diseases (depression, multiple sclerosis, Parkinson's and Alzheimer's). The report aims to explore whether drugs can influence the development and progression of brain diseases via the MGBA. Central findings indicate that all explored drugs induce dysbiosis. These dysbiosis patterns were associated with brain disorders. The influence on brain diseases varied across different bacterial taxa, possibly mediated by direct effects or through bacterial metabolites. Each drug induced both positive and negative changes in the abundance of bacteria, indicating a counterbalancing effect. Moreover, the above-mentioned drugs exhibited similar effects, suggesting that they may counteract or enhance each other's effects on brain diseases when taken together by comorbid patients. In conclusion, the interplay of bacterial species and their abundances may have a greater impact on brain diseases than individual drugs or bacterial strains. Future research is needed to better understand drug-induced dysbiosis and the implications for brain disease pathogenesis, with the potential to develop more effective therapeutic options for patients with brain-related diseases.

Antibiotic induced adipose tissue browning in C57BL/6 mice: An association with the metabolic profile and the gut microbiota.

AIMS: The use of antibiotics affects health. The gut microbial dysbiosis by antibiotics is thought to be an essential pathway to influence health. It is important to have optimized energy utilization, in which adipose tissues (AT) play crucial roles in maintaining health. Adipocytes regulate the balance between energy expenditure and storage. While it is known that white adipose tissue (WAT) stores energy and brown adipose tissue (BAT) produces energy by thermogenesis, the role of an intermediate AT plays an important role in balancing host internal energy. In the current study, we tried to understand how treating an antibiotic cocktail transforms WAT into BAT or, more precisely, into beige adipose tissue (BeAT). METHODS: Since antibiotic treatment perturbs the host microbiota, we wanted to understand the role of gut microbial dysbiosis in transforming WAT into BeAT in C57BL/6 mice. We further correlated the metabolic profile at the systemic level with this BeAT transformation and gut microbiota profile. KEY FINDINGS: In the present study, we have reported that the antibiotic cocktail treatment increases the Proteobacteria and Actinobacteria while reducing the Bacteroidetes phylum. We observed that prolonged antibiotic treatment could induce the formation of BeAT in the inguinal and perigonadal AT. The correlation analysis showed an association between the gut microbiota phyla, beige adipose tissue markers, and serum metabolites. SIGNIFICANCE: Our study revealed that the gut microbiota has a significant role in regulating the metabolic health of the host via microbiota-adipose axis communication.

Implication of intestinal microbiota in the etiopathogenesis of fibromyalgia: A systematic review.

Fibromyalgia (FM) is a highly prevalent chronic disease. About 4.7% of the world's population suffers from generalized pain and hypersensitivity, in addition to a wide range of physical and psychological symptoms. The etiopathogenesis of this disease is multifactorial, which makes its diagnosis and treatment challenging. Recently, the increase in the number of studies on microbiota has provided new data that can help to understand the onset and development of FM. An updated systematic review of the causes of FM has been carried out in this work. Particularly in the last decade, research has focused on the gut-brain axis, which has emerged as a crucial mechanism for microbiota-host crosstalk. In FM patients, quantitative imbalances of the intestinal microbiota (dysbiosis) and bacterial metabolites with differential relative abundance have been found, especially short-chain fatty acids and lipopolysaccharides. Furthermore, the microbiota has been found to indirectly influence host neurotransmitter mechanisms, mainly through the serotonin precursor, glutamate, and gamma-aminobutyric acid. Thus, all these mechanisms and their influence on the etiopathogenesis of FM are discussed in this review.

Lead exposure aggravates glucose metabolism disorders through gut microbiota dysbiosis and intestinal barrier damage in high-fat diet-fed mice.

BACKGROUND: Lead (Pb) is an ancient toxic metal and is still a major public health issue. Our previous study found that Pb exposure promotes metabolic disorders in obese mice, but the molecular mechanisms remain unclear. The present study explored the effects of Pb exposure on glucose homeostasis in mice fed a normal diet (ND) and high-fat diet (HFD) from the perspective of gut microbiota. RESULTS: Pb exposure had little effect on glucose metabolism in ND mice, but exacerbated hyperglycemia and insulin resistance, and impaired glucose tolerance in HFD mice. Pb exposure impaired intestinal tight junctions and mucin expression in HFD mice, increasing intestinal permeability and inflammation. Moreover, Pb exposure altered the composition and structure of the gut microbiota and decreased short-chain fatty acids (SCFAs) levels in HFD mice. Correlation analysis revealed that the gut microbiota and SCFAs were significantly correlated with the gut barrier and glucose homeostasis. Furthermore, the fecal microbiota transplantation from Pb-exposed HFD mice resulted in glucose homeostasis imbalance, intestinal mucosal structural damage and inflammation in recipient mice. However, Pb did not exacerbate the metabolic toxicity in HFD mice under depleted gut microbiota. CONCLUSION: The findings of the present study suggest that Pb induces impairment of glucose metabolism in HFD mice by perturbing the gut microbiota. Our study offers new perspectives on the mechanisms of metabolic toxicity of heavy metals and demonstrates that the gut microbiota may be a target of action for heavy metal exposure. © 2023 Society of Chemical Industry.

Impacts of gut microbiota alteration on age-related chronic liver diseases.

The gut microbiome and its metabolites are involved in developing and progressing liver disease. Various liver illnesses, such as non-alcoholic fatty liver disease, alcoholic liver disease, hepatitis C, and hepatocellular carcinoma, are made worse and have worse prognoses with aging. Dysbiosis, which occurs when the symbiosis between the microbiota and the host is disrupted, can significantly negatively impact health. Liver disease is linked to qualitative changes, such as an increase in hazardous bacteria and a decrease in good bacteria, as well as quantitative changes in the overall amount of bacteria (overgrowth). Intestinal gut microbiota and their metabolites may lead to chronic liver disease development through various mechanisms, such as increasing gut permeability, persistent systemic inflammation, production of SCFA, bile acids, and alteration in metabolism. Age-related gut dysbiosis can disrupt the communication between gut microbiota and the host, impacting the host's health and lifespan. With aging, a gradual loss of the ability to maintain homeostasis because of structural alteration and gut dysbiosis leads to the disease progression in end-stage liver disease. Recently chronic liver disease has been identified as a global problem. A large number of patients are receiving liver transplants yearly. Thereby gut microbiome ecology is changing in the patients of the gut due to the changes in pathophysiology during the preoperative stage. The present review summarises the age-associated dysbiosis of gut microbial composition and its contribution to chronic liver disease. This review also provides information about the impact of liver transplant on the gut microbiome and possible disadvantageous effects of alteration in gut microbiota.

Effect of chronic low-dose treatment with chitooligosaccharides on microbial dysbiosis and inflammation associated chronic ulcerative colitis in Balb/c mice.

The study aimed to investigate the potential of low dose chitooligosaccharide (COS) in ameliorating dextran sodium sulfate (DSS) induced chronic colitis by regulating microbial dysbiosis and pro-inflammatory responses. Chronic colitis was induced in BALB/c mice by DSS (4% w/v, 3 cycles of 5 days) administration. The mice were divided into four groups: vehicle, DSS, DSS + mesalamine and DSS+COS. COS and mesalamine were administered orally, daily once, from day 1 to day 30 at a dose of 20 mg/kg and 50 mg/kg respectively. The disease activity index (DAI), colon length, histopathological score, microbial composition, and pro-inflammatory cytokine expression were evaluated. COS (20 mg/kg, COSLow) administration reduced the disease activity index, and colon shortening, caused by DSS significantly. Furthermore, COSLow restored the altered microbiome in the gut and inhibited the elevated pro-inflammatory cytokines (IL-1 and IL-6) in the colon against DSS-induced chronic colitis in mice. Moreover, COSLow treatment improved the probiotic microflora thereby restoring the gut homeostasis. In conclusion, this is the first study where microbial dysbiosis and pro-inflammatory responses were modulated by chronic COSLow treatment against DSS-induced chronic colitis in Balb/c mice. Therefore, COS supplementation at a relatively low dose could be efficacious for chronic inflammatory bowel disease.