scholarly journals Gut microbiome and metabolome in a non-human primate model of chronic excessive alcohol drinking

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daria Piacentino ◽  
Silvia Grant-Beurmann ◽  
Carlotta Vizioli ◽  
Xiaobai Li ◽  
Catherine F. Moore ◽  
...  
Keyword(s):  
Amino Acids ◽  
Alcohol Use ◽  
Alcohol Drinking ◽  
Gut Microbiome ◽  
Alcohol Exposure ◽  
Primate Model ◽  
Fecal Microbiome ◽  
Excessive Alcohol ◽  
Human Primate

AbstractA relationship between the gut microbiome and alcohol use disorder has been suggested. Excessive alcohol use produces changes in the fecal microbiome and metabolome in both rodents and humans. Yet, these changes can be observed only in a subgroup of the studied populations, and reversal does not always occur after abstinence. We aimed to analyze fecal microbial composition and function in a translationally relevant baboon model of chronic heavy drinking that also meets binge criteria (drinking too much, too fast, and too often), i.e., alcohol ~1 g/kg and blood alcohol levels (BALs) ≥ 0.08 g/dL in a 2-hour period, daily, for years. We compared three groups of male baboons (Papio anubis): L = Long-term alcohol drinking group (12.1 years); S = Short-term alcohol drinking group (2.7 years); and C = Control group, drinking a non-alcoholic reinforcer (Tang®) (8.2 years). Fecal collection took place during 3 days of Drinking (D), followed by a short period (3 days) of Abstinence (A). Fecal microbial alpha- and beta-diversity were significantly lower in L vs. S and C (p’s < 0.05). Members of the commensal families Lachnospiraceae and Prevotellaceae showed a relative decrease, whereas the opportunistic pathogen Streptococcus genus showed a relative increase in L vs. S and C (p’s < 0.05). Microbiota-related metabolites of aromatic amino acids, tricarboxylic acid cycle, and pentose increased in L vs. S and C (FDR-corrected p < 0.01), with the latter two suggesting high energy metabolism and enhanced glycolysis in the gut lumen in response to alcohol. Consistent with the long-term alcohol exposure, mucosal damage and oxidative stress markers (N-acetylated amino acids, 2-hydroxybutyrate, and metabolites of the methionine cycle) increased in L vs. S and C (FDR-corrected p < 0.01). Overall, S showed few differences vs. C, possibly due to the long-term, chronic alcohol exposure needed to alter the normal gut microbiota. In the three groups, the fecal microbiome barely differed between conditions D and A, whereas the metabolome shifted in the transition from condition D to A. In conclusion, changes in the fecal microbiome and metabolome occur after significant long-term excessive drinking and are only partially affected by acute forced abstinence from alcohol. These results provide novel information on the relationship between the fecal microbiome and metabolome in a controlled experimental setting and using a unique non-human primate model of chronic excessive alcohol drinking.

scholarly journals Gut Microbiome Changes Associated with Epithelial Barrier Damage and Systemic Inflammation during Antiretroviral Therapy of Chronic SIV Infection

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1567
Author(s):  
Ceylan Tanes ◽  
Edith M. Walker ◽  
Nadia Slisarenko ◽  
Giovanni L. Gerrets ◽  
Brooke F. Grasperge ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Systemic Inflammation ◽  
Gut Microbiome ◽  
Epithelial Barrier ◽  
Partial Recovery ◽  
Primate Model ◽  
Fecal Microbiome ◽  
Siv Infection

Gut dysbiosis is a common feature associated with the chronic inflammation of HIV infection. Toward understanding the interplay of chronic treated HIV infection, dysbiosis, and systemic inflammation, we investigated longitudinal fecal microbiome changes and plasma inflammatory markers in the nonhuman primate model. Following simian immunodeficiency virus (SIV) infection in rhesus macaques, significant changes were observed in several members of the phylum Firmicutes along with an increase in Bacteroidetes. Viral suppression with antiretroviral therapy (ART) resulted in an early but partial recovery of compositional changes and butyrate producing genes in the gut microbiome. Over the course of chronic SIV infection and long-term ART, however, the specific loss of Faecalibacterium prausnitzii and Treponema succinifaciens significantly correlated with an increase in plasma inflammatory cytokines including IL-6, G-CSF, I-TAC, and MIG. Further, the loss of T. succinifaciens correlated with an increase in circulating biomarkers of gut epithelial barrier damage (IFABP) and microbial translocation (LBP and sCD14). As F. prausnitzii and T. succinifaciens are major short-chain fatty acid producing bacteria, their sustained loss during chronic SV-ART may contribute to gut inflammation and metabolic alterations despite effective long-term control of viremia. A better understanding of the correlations between the anti-inflammatory bacterial community and healthy gut barrier functions in the setting of long-term ART may have a major impact on the clinical management of inflammatory comorbidities in HIV-infected individuals.

scholarly journals Selective intra-arterial brain cooling improves long-term outcomes in a non-human primate model of embolic stroke: Efficacy depending on reperfusion status

2020 ◽  
Vol 40 (7) ◽  
pp. 1415-1426 ◽  
Author(s):  
Di Wu ◽  
Jian Chen ◽  
Mohammed Hussain ◽  
Longfei Wu ◽  
Jingfei Shi ◽  
...  
Keyword(s):  
Rhesus Macaques ◽  
Motor Dysfunction ◽  
Neurological Deficits ◽  
Brain Cooling ◽  
Long Term Outcomes ◽  
Primate Model ◽  
Tissue Plasminogen ◽  
Human Primate ◽  
Arterial Thrombolysis

Nearly all stroke neuroprotection modalities, including selective intra-arterial cooling (SI-AC), have failed to be translated from bench to bed side. Potentially overlooked reasons may be biological gaps, inadequate attention to reperfusion states and mismatched attention to neurological benefits. To advance stroke translation, we describe a novel thrombus-based stroke model in adult rhesus macaques. Intra-arterial thrombolysis with tissue plasminogen activator leads to three clinically relevant outcomes – complete, partial, and no recanalization based on digital subtraction angiography. We also find reperfusion as a prerequisite for SI-AC-induced benefits, in which models with complete or partial reperfusion exhibit significantly reduced infarct volumes, mitigated neurological deficits, improved upper limb motor dysfunction in both acute and chronic stages; however, no further neuroprotection is observed in those without reperfusion. In summary, we discover reperfusion as a crucial regulator of SI-AC-induced neuroprotection and provide insights of long-term functional benefits in behavior and imaging levels. Our findings could be important not only for the translational prerequisite and potential molecular targets, but also for this thrombus-thrombolysis model in monkeys as a powerful tool for further translational stroke studies.

scholarly journals Persistence of Supplemented Bifidobacterium longum subsp. infantis EVC001 in Breastfed Infants

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Steven A. Frese ◽  
Andra A. Hutton ◽  
Lindsey N. Contreras ◽  
Claire A. Shaw ◽  
Michelle C. Palumbo ◽  
...  
Keyword(s):  
Human Milk ◽  
Gut Microbiome ◽  
Bifidobacterium Longum ◽  
Specific Substrate ◽  
Fecal Microbiome ◽  
Microbiome Composition ◽  
Breastfed Infants ◽  
Gut Function ◽  
First Time

ABSTRACT The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of B. infantis EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by B. infantis EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated Bifidobacterium sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function. Attempts to alter intestinal dysbiosis via administration of probiotics have consistently shown that colonization with the administered microbes is transient. This study sought to determine whether provision of an initial course of Bifidobacterium longum subsp. infantis (B. infantis) would lead to persistent colonization of the probiotic organism in breastfed infants. Mothers intending to breastfeed were recruited and provided with lactation support. One group of mothers fed B. infantis EVC001 to their infants from day 7 to day 28 of life (n = 34), and the second group did not administer any probiotic (n = 32). Fecal samples were collected during the first 60 postnatal days in both groups. Fecal samples were assessed by 16S rRNA gene sequencing, quantitative PCR, mass spectrometry, and endotoxin measurement. B. infantis-fed infants had significantly higher populations of fecal Bifidobacteriaceae, in particular B. infantis, while EVC001 was fed, and this difference persisted more than 30 days after EVC001 supplementation ceased. Fecal milk oligosaccharides were significantly lower in B. infantis EVC001-fed infants, demonstrating higher consumption of human milk oligosaccharides by B. infantis EVC001. Concentrations of acetate and lactate were significantly higher and fecal pH was significantly lower in infants fed EVC001, demonstrating alterations in intestinal fermentation. Infants colonized by Bifidobacteriaceae at high levels had 4-fold-lower fecal endotoxin levels, consistent with observed lower levels of Gram-negative Proteobacteria and Bacteroidetes. IMPORTANCE The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of B. infantis EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by B. infantis EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated Bifidobacterium sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function.

scholarly journals Weaning age and its effect on the development of the swine gut microbiome and resistome

2021 ◽  
Author(s):  
Devin B Holman ◽  
Katherine E Gzyl ◽  
Kathy T Mou ◽  
Heather K Allen
Keyword(s):  
Relative Abundance ◽  
Gut Microbiome ◽  
Rrna Gene ◽  
Metagenomic Sequencing ◽  
Carbohydrate Active Enzymes ◽  
Fecal Microbiome ◽  
Shotgun Metagenomic Sequencing ◽  
Swine Operations ◽  
Weaning Age

Piglets are often weaned between 19 and 22 d of age in North America although in some swine operations this may occur at 14 d or less. Piglets are abruptly separated from their sow at weaning and are quickly transitioned from sow's milk to a plant-based diet. The effect of weaning age on the long-term development of the pig gut microbiome is largely unknown. In this study, pigs were weaned at either 14, 21, or 28 d of age and fecal samples collected 21 times from d 4 (neonatal) through to marketing at d 140. The fecal microbiome was characterized using 16S rRNA gene and shotgun metagenomic sequencing. The fecal microbiome of all piglets shifted significantly three to seven days post-weaning with an increase in microbial diversity. Several Prevotella spp. increased in relative abundance immediately after weaning as did butyrate-producing species such as Butyricicoccus porcorum, Faecalibacterium prausnitzii, and Megasphaera elsdenii. Within 7 days of weaning, the gut microbiome of pigs weaned at 21 and 28 days of age resembled that of pigs weaned at 14 d. Resistance genes to most antimicrobial classes decreased in relative abundance post-weaning with the exception of those conferring resistance to tetracyclines and macrolides-lincosamides-streptogramin B. The relative abundance of microbial carbohydrate-active enzymes (CAZymes) changed significantly in the post-weaning period with an enrichment of CAZymes involved in degradation of plant-derived polysaccharides. These results demonstrate that pigs tend to have a more similar microbiome as they age and that weaning age has only a temporary effect on the gut microbiome.

scholarly journals Simulated manned Mars exploration: effects of dietary and diurnal cycle variations on the gut microbiome of crew members in a controlled ecological life support system

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7762 ◽  
Author(s):  
Hai-Sheng Dong ◽  
Pu Chen ◽  
Yan-Bo Yu ◽  
Peng Zang ◽  
Zhao Wei
Keyword(s):  
Support System ◽  
Gut Microbiome ◽  
Large Scale ◽  
Life Support ◽  
Alpha Diversity ◽  
Life Support System ◽  
Fecal Microbiome ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D

Background Changes in gut microbiome are closely related to dietary and environment variations, and diurnal circle interventions impact on human metabolism and the microbiome. Changes in human gut microbiome and serum biochemical parameters during long-term isolation in a controlled ecological life support system (CELSS) are of great significance for maintaining the health of crewmembers. The Green Star 180 project performed an integrated study involving a four-person, 180-day duration assessment in a CELSS, during which variations in gut microbiome and the concentration of serum 25-hydroxyvitamin D, α-tocopherol, retinol and folic acid from the crewmembers were determined. Results Energy intake and body mass index decreased during the experiment. A trade-off between Firmicutes and Bacteroidetes during the study period was observed. Dynamic variations in the two dominant genus Bacteroides and Prevotella indicated a variation of enterotypes. Both the evenness and richness of the fecal microbiome decreased during the isolation in the CELSS. Transition of diurnal circle from Earth to Mars increased the abundance of Fusobacteria phylum and decreased alpha diversity of the fecal microbiome. The levels of serum 25-hydroxyvitamin D in the CELSS were significantly lower than those outside the CELSS. Conclusions The unique isolation process in the CELSS led to a loss of alpha diversity and a transition of enterotypes between Bacteroides and Prevotella. Attention should therefore be paid to the transition of the diurnal circle and its effects on the gut microbiome during manned Mars explorations. In particular, serum 25-hydroxyvitamin D levels require monitoring under artificial light environments and during long-term space flight. Large-scale studies are required to further consolidate our findings.

scholarly journals Detangling Diet from Obesity Effects on the Gut Microbiome and Metabolic Parameters Using a Non-Human Primate Model

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1583-1583
Author(s):  
Carol Shively ◽  
Kenysha Clear ◽  
Katherine Cook
Keyword(s):  
Gut Microbiota ◽  
Body Fat ◽  
Gut Microbiome ◽  
Western Diet ◽  
Metabolic Parameters ◽  
Primate Model ◽  
Body Adiposity ◽  
Α Diversity ◽  
The Impact ◽  
Human Primate

Abstract Objectives Poor diet and obesity often go hand-in-hand and are difficult to discern which variable is the major driver of the gut microbiome. The objective of this study was to determine the impact of obesity within dietary exposures on the gut microbiome and metabolic parameters using a non-human primate model. Methods Female M. fasicularis monkeys were fed a Western or Mediterranean diet for 2.5 years. We performed metagenomics sequencing on fecal samples obtained at 26 months. DNA was isolated from feces using Qiagen PowerSoil DNA extraction kit and metagenomics sequencing was performed for multikingdom microbiome analysis. DEXA scans for body adiposity and metabolic profiling were measured in each subject before the end of the study. Subjects were grouped by body fat composition (Lean (≤10% body fat) or Overweight/Obese (≥20% body fat)) and the impact of diet and adiposity was determine on the gut microbiome. Gut microbiota populations were correlated with metabolic parameters. Results Diet is the main determinant on gut microbiome α-diversity. Obesity had no significant outcome on Shannon diversity. Obesity within each dietary pattern can influence certain gut microbes. Lean Mediterranean diet-fed animals had significantly higher L. animals and C. comes that overweight animals fed the same diet. Obese Western diet-fed animals displayed elevated proportional abundance of S. infantarius and R. chanpaneliensis that lean Western diet-fed animals. Independent of adiposity, Western diet consumption lead to two distinct microbiome populations; P. copri high and P. copri low. P. copriHIGH displayed reduced α-diversity, increased abundance of other Prevotella species (P. stercorea, P. brevis, and P. bryantii), and increased F. prausnitzii. P. copri negatively correlated with α-diversity. P. copriLOW displayed increased proportional abundance of E. siraeum. Gut E. siraeum populations positively correlated with plasma HDL cholesterol levels. Conclusions Our data indicates that diet is a potent regulator of the gut microbiome, while body adiposity can subtly shift specific gut microbiota taxa within subjects fed a specific dietary pattern. Moreover, our data indicates at a sub-group of metabolically healthier subjects on a Western diet characterized by low P. copri microbiota abundance. Funding Sources NIH and DOD BCRP.

scholarly journals Long-term epigenetic changes in offspring mice exposed to alcohol during gestation and lactation

2019 ◽  
Vol 33 (12) ◽  
pp. 1562-1572 ◽  
Author(s):  
Lídia Cantacorps ◽  
Silvia Alfonso-Loeches ◽  
Consuelo Guerri ◽  
Olga Valverde
Keyword(s):  
Prefrontal Cortex ◽  
Alcohol Drinking ◽  
Alcohol Exposure ◽  
Learning Task ◽  
Spectrum Disorder ◽  
Epigenetic Changes ◽  
Histone H4 ◽  
Spectrum Disorders ◽  
Foetal Alcohol Spectrum Disorders

Background: Alcohol exposure impairs brain development and leads to a range of behavioural and cognitive dysfunctions, termed as foetal alcohol spectrum disorders. Although different mechanisms have been proposed to participate in foetal alcohol spectrum disorders, the molecular insights of such effects are still uncertain. Using a mouse model of foetal alcohol spectrum disorder, we have previously shown that maternal binge-like alcohol drinking causes persistent effects on motor, cognitive and emotional-related behaviours associated with neuroimmune dysfunctions. Aims: In this study, we sought to evaluate whether the long-term behavioural alterations found in offspring with early exposure to alcohol are associated with epigenetic changes in the hippocampus and prefrontal cortex. Methods: Pregnant C57BL/6 female mice underwent a model procedure for binge alcohol drinking throughout both the gestation and lactation periods. Subsequently, adult offspring were assessed for their cognitive function in a reversal learning task and brain areas were extracted for epigenetic analyses. Results: The results demonstrated that early binge alcohol exposure induces long-term behavioural effects along with alterations in histone acetylation (histone H4 lysine 5 and histone H4 lysine 12) in the hippocampus and prefrontal cortex. The epigenetic effects were linked with an imbalance in histone acetyltransferase activity that was found to be increased in the prefrontal cortex of mice exposed to alcohol. Conclusions: In conclusion, our results reveal that maternal binge-like alcohol consumption induces persistent epigenetic modifications, effects that might be associated with the long-term cognitive and behavioural impairments observed in foetal alcohol spectrum disorder models.

scholarly journals First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model

2017 ◽  
Vol 216 (3) ◽  
pp. 302.e1-302.e8 ◽  
Author(s):  
Jamie O. Lo ◽  
Matthias C. Schabel ◽  
Victoria H.J. Roberts ◽  
Xiaojie Wang ◽  
Katherine S. Lewandowski ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Growth And Development ◽  
Alcohol Exposure ◽  
First Trimester ◽  
Oxygen Availability ◽  
Primate Model ◽  
Placental Perfusion ◽  
Human Primate

scholarly journals COVID-19 pandemic and alcohol: a problem beyond addiction and psychiatry

2020 ◽  
Vol 1 (2) ◽  
pp. 11-15
Author(s):  
Yury P. Sivolap ◽  
Keyword(s):  
Alcohol Use ◽  
Alcohol Abuse ◽  
Global Health ◽  
Significant Deterioration ◽  
Excessive Alcohol Consumption ◽  
Susceptibility To Infection ◽  
Number Of Patients ◽  
Special Programs ◽  
Excessive Alcohol

The increase in alcohol use during the COVID-19 pandemic is one of the major global health problems. Alcohol abuse is caused by many causes, including the stress associated with the pandemic. The problem of alcohol abuse is getting worse by the difficult access of patients to medical care, and lockdown, including a restrained sale of alcohol, can lead to numerous cases of severe alcohol withdrawal, alcohol psychosis and suicide. Excessive alcohol consumption reduces the immune system, increases susceptibility to infection, including SARS-CoV-2, and contributes to the severe course of COVID-19, increasing the likelihood of complications and death. It is assumed that alcohol abuse during the pandemic will have long-term adverse consequences in the form of significant deterioration of public health, an increase in the number of patients with alcohol dependence and alcoholic liver disease, and an excessive burden on global health. Experts justify the need to apply special programs to help people with alcohol use disorders during the pandemic and develop a set of preventive measures to prevent the adverse long-term consequences of excessive alcohol use.

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