Browsing by Subject "Gut microbiota"
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Item Adolescent alcohol drinking interaction with the gut microbiome: implications for adult alcohol use disorder(Frontiers Media, 2024) Getachew, Bruk; Hauser, Sheketha R.; Bennani, Samia; El Kouhen, Nacer; Sari, Youssef; Tizabi, Yousef; Psychiatry, School of MedicineReciprocal communication between the gut microbiota and the brain, commonly referred to as the “gut-brain-axis” is crucial in maintaining overall physiological homeostasis. Gut microbiota development and brain maturation (neuronal connectivity and plasticity) appear to be synchronized and to follow the same timeline during childhood (immature), adolescence (expansion) and adulthood (completion). It is important to note that the mesolimbic reward circuitry develops early on, whereas the maturation of the inhibitory frontal cortical neurons is delayed. This imbalance can lead to increased acquirement of reward-seeking and risk-taking behaviors during adolescence, and consequently eventuate in heightened risk for substance abuse. Thus, there is high initiation of alcohol drinking in early adolescence that significantly increases the risk of alcohol use disorder (AUD) in adulthood. The underlying causes for heightened AUD risk are not well understood. It is suggested that alcohol-associated gut microbiota impairment during adolescence plays a key role in AUD neurodevelopment in adulthood. Furthermore, alcohol-induced dysregulation of microglia, either directly or indirectly through interaction with gut microbiota, may be a critical neuroinflammatory pathway leading to neurodevelopmental impairments and AUD. In this review article, we highlight the influence of adolescent alcohol drinking on gut microbiota, gut-brain axis and microglia, and eventual manifestation of AUD. Furthermore, novel therapeutic interventions via gut microbiota manipulations are discussed briefly.Item Can you cause inflammatory bowel disease with fecal transplantation? A 31-patient case-series of fecal transplantation using stool from a donor who later developed Crohn's disease(Taylor & Francis, 2017-05-04) Fischer, Monika; Bittar, Mohamad; Papa, Eliseo; Kassam, Zain; Smith, Mark; Medicine, School of MedicineItem Dietary Phosphorus Levels Influence Protein-Derived Uremic Toxin Production in Nephrectomized Male Rats(MDPI, 2024-06-08) Cladis, Dennis P.; Burstad, Kendal M.; Biruete, Annabel; Jannasch, Amber H.; Cooper, Bruce R.; Hill Gallant, Kathleen M.; Nutrition and Dietetics, School of Health and Human SciencesGut microbiota-derived uremic toxins (UT) accumulate in patients with chronic kidney disease (CKD). Dietary phosphorus and protein restriction are common in CKD treatment, but the relationship between dietary phosphorus, a key nutrient for the gut microbiota, and protein-derived UT is poorly studied. Thus, we explored the relationship between dietary phosphorus and serum UT in CKD rats. For this exploratory study, we used serum samples from a larger study on the effects of dietary phosphorus on intestinal phosphorus absorption in nephrectomized (Nx, n = 22) or sham-operated (sham, n = 18) male Sprague Dawley rats. Rats were randomized to diet treatment groups of low or high phosphorus (0.1% or 1.2% w/w, respectively) for 1 week, with serum trimethylamine oxide (TMAO), indoxyl sulfate (IS), and p-cresol sulfate (pCS) analyzed by LC-MS. Nx rats had significantly higher levels of serum TMAO, IS, and pCS compared to sham rats (all p < 0.0001). IS showed a significant interaction between diet and CKD status, where serum IS was higher with the high-phosphorus diet in both Nx and sham rats, but to a greater extent in the Nx rats. Serum TMAO (p = 0.24) and pCS (p = 0.34) were not affected by dietary phosphorus levels. High dietary phosphorus intake for 1 week results in higher serum IS in both Nx and sham rats. The results of this exploratory study indicate that reducing dietary phosphorus intake in CKD may have beneficial effects on UT accumulation.Item Dynamic modulation of spleen germinal center reactions by gut bacteria during Plasmodium infection(Cell Press, 2021-05-11) Mandal, Rabindra K.; Denny, Joshua E.; Namazzi, Ruth; Opoka, Robert O.; Datta, Dibyadyuti; John, Chandy C.; Schmidt, Nathan W.; Pediatrics, School of MedicineGut microbiota educate the local and distal immune system in early life to imprint long-term immunological outcomes while maintaining the capacity to dynamically modulate the local mucosal immune system throughout life. It is unknown whether gut microbiota provide signals that dynamically regulate distal immune responses following an extra-gastrointestinal infection. We show here that gut bacteria composition correlated with the severity of malaria in children. Using the murine model of malaria, we demonstrate that parasite burden and spleen germinal center reactions are malleable to dynamic cues provided by gut bacteria. Whereas antibiotic-induced changes in gut bacteria have been associated with immunopathology or impairment of immunity, the data demonstrate that antibiotic-induced changes in gut bacteria can enhance immunity to Plasmodium. This effect is not universal but depends on baseline gut bacteria composition. These data demonstrate the dynamic communications that exist among gut bacteria, the gut-distal immune system, and control of Plasmodium infection.Item Gut microbiota was modulated by moxibustion stimulation in rats with irritable bowel syndrome(Biomed Central, 2018-12-18) Wang, Xiaomei; Qi, Qin; Wang, Yuanyuan; Wu, Huangan; Jin, Xiaoming; Yao, Huan; Jin, Duiyin; Liu, Yanan; Wang, Cun; Anatomy and Cell Biology, IU School of MedicineBackground: The pathogenesis of irritable bowel syndrome (IBS) is closely related to intestinal dysbacteriosis and can be controlled by moxibustion treatment. However, the mechanism underlying the therapeutic value of moxibustion in IBS treatment remains unknown. Methods: An IBS rat model was established by colorectal distention (CRD) stimulus and mustard oil clyster. Sixty-five male rats were randomly divided into six groups: normal, IBS model, moxibustion, electroacupuncture (EA), Bifid-triple Viable Capsule (BTVC) and Pinaverium Bromide (PB) groups. The moxibustion group was treated with mild moxibustion at the bilateral Tianshu (ST25) and Shangjuxu (ST37) for 10 min/day for 7 days, the EA group was given EA at ST25 and ST37 once daily for 7 days, while the BTVC group and PB groups received Bifid-triple Viable Capsule and Pinaverium Bromide solution (at the proportion of 1:0.018) respectively by gavage once daily for 7 days. After the treatment, abdominal withdrawal reflex (AWR) scores were determined based on CRD stimulus, gut microbiota profiling was conducted by 16S rRNA high-throughput sequencing. Results: Irritable bowel syndrome model rats had significantly increased AWR scores at all intensities (20, 40, 60 and 80 mmHg) compared with the normal group. Moxibustion treatment significantly reduced AWR scores compared with the IBS model group at all intensities. Across all groups the most abundant phyla were Bacteroidetes and Firmicutes followed by Proteobacteria and Candidatus Saccharibacteria. At genus level IBS model rats had a higher abundance of Prevotella, Bacteroides and Clostridium XI and a lower abundance of Lactobacillus and Clostridium XIVa compared with normal rats. These changes in microbiota profiles could however be reversed by moxibustion treatment. Alpha diversity was decreased in IBS model rats compared with normal rats, yet significantly increased in moxibustion- and PB-treated rats compared with IBS rats. Conclusion: Our findings suggest that moxibustion treats IBS by modulating the gut microbiota.Item Identification of Gut Microbial Lysine and Histidine Degradation and CYP-Dependent Metabolites as Biomarkers of Fatty Liver Disease(American Society for Microbiology, 2023) Driuchina, Anastasiia; Hintikka, Jukka; Lehtonen, Marko; Keski-Rahkonen, Pekka; O’Connell, Thomas; Juvonen, Risto; Kuula, Juho; Hakkarainen, Antti; Laukkanen, Jari A.; Mäkinen, Elina; Lensu, Sanna; Pietiläinen, Kirsi H.; Pekkala, Satu; Otolaryngology -- Head and Neck Surgery, School of MedicineNumerous studies have described specific metabolites as biomarkers of severe liver diseases, but very few have measured gut microbiota (GM)-produced metabolites in fatty liver disease. We aimed at finding GM signatures and metabolite markers in plasma and feces related to high liver fat content. Based on imaging, we divided study participants into low (<5%, LF, n = 25) and high (>5%, HF, n = 39) liver fat groups. Fecal (LF n = 14, HF n = 25) and plasma (LF n = 11, HF n = 7) metabolomes of subsets of participants were studied using liquid chromatography/high resolution mass spectrometry. The GM were analyzed using 16S rRNA gene sequencing. Additionally, blood clinical variables and diet were studied. Dyslipidemia, higher liver enzymes and insulin resistance characterized the HF group. No major differences in diet were found between the groups. In the GM, the HF group had lower abundance of Bacteroides and Prevotellaceae NK3B31 group than the LF group after adjusting for metformin use or obesity. In feces, the HF group had higher levels of lysine and histidine degradation products, while 6-hydroxybetatestosterone (metabolized by CYP3A4) was low. Higher plasma levels of caffeine and its metabolites in the HF group indicate that the activity of hepatic CYP1A2 was lower than in the LF group. Our results suggest, that low fecal Prevotellaceae NK3B31 and Bacteroides abundance, and increased lysine and histidine degradation may serve as GM biomarkers of high liver fat. Altered plasma caffeine metabolites and lowered testosterone metabolism may specify decreased CYP activities, and their potential utility, as biomarkers of fatty liver disease.Item Impact of diet on hydrogen sulfide production: implications for gut health(Wolters Kluwer, 2023) Teigen, Levi; Biruete, Annabel; Khoruts, Alexander; Medicine, School of MedicinePurpose of review: Excessive hydrogen sulfide (H 2 S) production by the gut microbiota may contribute to the pathogenesis of multiple intestinal diseases, including colon cancer and ulcerative colitis. Therefore, understanding of dietary drivers of H 2 S production has potential implications for nutritional strategies to optimize gut health and treat intestinal diseases. Recent findings: Recent studies support a positive relationship between dietary protein intake and H 2 S production. However, protein rarely exists in isolation in the diet, and dietary fiber intake could reduce H 2 S production in humans and animals, even with ∼30% of calories derived from protein. Summary: These findings suggest that increased fiber intake may reduce H 2 S production irrespective of protein intake, enabling the ability to meet the metabolic demands of the illness while supporting gut health. Here we discuss two recent ulcerative colitis diet studies that illustrate this point.Item Multi-modal Single-Cell Analysis Reveals Brain Immune Landscape Plasticity during Aging and Gut Microbiota Dysbiosis(Elsevier, 2020-12-01) Golomb, Samantha M.; Guldner, Ian H.; Zhao, Anqi; Wang, Qingfei; Palakurthi, Bhavana; Aleksandrovic, Emilija A.; Lopez, Jacqueline A.; Lee, Shaun W.; Yang, Kai; Zhang, Siyuan; Medicine, School of MedicinePhenotypic and functional plasticity of brain immune cells contribute to brain tissue homeostasis and disease. Immune cell plasticity is profoundly influenced by tissue microenvironment cues and systemic factors. Aging and gut microbiota dysbiosis that reshape brain immune cell plasticity and homeostasis has not been fully delineated. Using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq), we analyze compositional and transcriptional changes of the brain immune landscape in response to aging and gut dysbiosis. Discordance between canonical surface-marker-defined immune cell types and their transcriptomes suggest transcriptional plasticity among immune cells. Ly6C+ monocytes predominate a pro-inflammatory signature in the aged brain, while innate lymphoid cells (ILCs) shift toward an ILC2-like profile. Aging increases ILC-like cells expressing a T memory stemness (Tscm) signature, which is reduced through antibiotics-induced gut dysbiosis. Systemic changes due to aging and gut dysbiosis increase propensity for neuroinflammation, providing insights into gut dysbiosis in age-related neurological diseases.Item Oxidized Derivatives of Linoleic Acid in Pediatric Metabolic Syndrome: Is Their Pathogenic Role Modulated by the Genetic Background and the Gut Microbiota?(Mary Ann Liebert, 2018-11-30) Tricò, Domenico; Di Sessa, Anna; Caprio, Sonia; Chalasani, Naga; Liu, Wanqing; Liang, Tiebing; Graf, Joerg; Herzog, Raimund I.; Johnson, Casey D.; Umano, Giuseppina Rosaria; Feldstein, Ariel E.; Santoro, Nicola; Medicine, School of MedicineWe tested whether oxidized linoleic acid metabolites (OXLAM) are associated with pediatric metabolic syndrome (MetS) and a proatherogenic lipoprotein profile in 122 obese adolescents. Furthermore, we examined whether genetic and metagenomic factors can modulate plasma OXLAM concentrations by genotyping the fatty acid desaturase 1/2 (FADS) gene and by characterizing the gut microbiota. Subjects with MetS (n = 50) showed higher concentrations of 9- and 13-oxo-octadecadienoic acid (9- and 13-oxo-ODE) than subjects without MetS (n = 72). Both metabolites were associated with an adverse lipoprotein profile that was characterized by elevated very small-dense low-density lipoprotein (p < 0.005) and large very low-density lipoprotein particles (p = 0.01). Plasma 9- and 13-oxo-ODE were higher in subjects carrying the haplotype AA of the FADS gene cluster (p = 0.030 and p = 0.048, respectively). Furthermore, the reduced gut bacterial load was associated with higher 9-oxo-ODE concentrations (p = 0.035). This is the first study showing that high plasma OXLAM concentrations are associated with MetS and suggesting that the leading factors for high plasma concentrations of OXLAM might be the genetic background and the composition of the gut microbiota. In conclusion, high concentrations of 9- and 13-oxo-ODE, which may be the result of a genetic predisposition and a reduced gut bacterial load, are associated with MetS and with a proatherogenic lipoprotein profile in obese adolescents.Item Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction(MDPI, 2024-05-30) Tizabi, Yousef; Getachew, Bruk; Hauser, Sheketha R.; Tsytsarev, Vassiliy; Manhães, Alex C.; da Silva, Victor Diogenes Amaral; Psychiatry, School of MedicineMood disorders and substance use disorder (SUD) are of immense medical and social concern. Although significant progress on neuronal involvement in mood and reward circuitries has been achieved, it is only relatively recently that the role of glia in these disorders has attracted attention. Detailed understanding of the glial functions in these devastating diseases could offer novel interventions. Here, following a brief review of circuitries involved in mood regulation and reward perception, the specific contributions of neurotrophic factors, neuroinflammation, and gut microbiota to these diseases are highlighted. In this context, the role of specific glial cells (e.g., microglia, astroglia, oligodendrocytes, and synantocytes) on phenotypic manifestation of mood disorders or SUD are emphasized. In addition, use of this knowledge in the potential development of novel therapeutics is touched upon.