Gut Microbiome Changes Associated with Epithelial Barrier Damage and Systemic Inflammation during Antiretroviral Therapy of Chronic 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.

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

Translational Psychiatry ◽

10.1038/s41398-021-01728-6 ◽

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.

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Development of Non-Hodgkin Lymphoma in a Cohort of Patients with Severe Human Immunodeficiency Virus (HIV) Infection on Long-Term Antiretroviral Therapy

Annals of Internal Medicine ◽

10.7326/0003-4819-113-4-276 ◽

1990 ◽

Vol 113 (4) ◽

pp. 276 ◽

Cited By ~ 189

Author(s):

James M. Pluda

Keyword(s):

Human Immunodeficiency Virus ◽

Antiretroviral Therapy ◽

Hiv Infection ◽

Hodgkin Lymphoma ◽

Non Hodgkin Lymphoma ◽

Immunodeficiency Virus

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

mSphere ◽

10.1128/msphere.00501-17 ◽

2017 ◽

Vol 2 (6) ◽

Cited By ~ 49

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.

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Long-term HIV infection and antiretroviral therapy are associated with bone microstructure alterations in premenopausal women

Osteoporosis International ◽

10.1007/s00198-012-2189-1 ◽

2012 ◽

Vol 24 (6) ◽

pp. 1843-1852 ◽

Cited By ~ 21

Author(s):

A. Calmy ◽

T. Chevalley ◽

C. Delhumeau ◽

L. Toutous-Trellu ◽

R. Spycher-Elbes ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Hiv Infection ◽

Premenopausal Women ◽

Bone Microstructure

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

10.1101/2021.05.20.444551 ◽

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.

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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 ◽

10.7717/peerj.7762 ◽

2019 ◽

Vol 7 ◽

pp. e7762 ◽

Cited By ~ 2

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.

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Corrigendum to: Impact of Acute HIV Infection and Early Antiretroviral Therapy on the Human Gut Microbiome

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa381 ◽

2020 ◽

Vol 7 (9) ◽

Author(s):

Ornella Sortino ◽

Nittaya Phanuphak ◽

Alexandra Schuetz ◽

Alexandra M Ortiz ◽

Nitiya Chomchey ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Hiv Infection ◽

Gut Microbiome ◽

Human Gut ◽

Acute Hiv Infection ◽

Human Gut Microbiome ◽

Acute Hiv

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Long-Term Cocaine Use and Antiretroviral Therapy Are Associated with Silent Coronary Artery Disease in African Americans with HIV Infection Who Have No Cardiovascular Symptoms

Clinical Infectious Diseases ◽

10.1086/526782 ◽

2008 ◽

Vol 46 (4) ◽

pp. 600-610 ◽

Cited By ~ 26

Author(s):

S. Lai ◽

E. K. Fishman ◽

H. Lai ◽

R. Moore ◽

J. Cofrancesco ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Antiretroviral Therapy ◽

African Americans ◽

Hiv Infection ◽

Cocaine Use ◽

Silent Coronary Artery Disease ◽

Artery Disease

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Immunodeficiency lentiviral infections in natural and non-natural hosts

Blood ◽

10.1182/blood-2010-12-325936 ◽

2011 ◽

Vol 118 (4) ◽

pp. 847-854 ◽

Cited By ~ 37

Author(s):

Jason M. Brenchley ◽

Mirko Paiardini

Keyword(s):

Hiv Infection ◽

Nonhuman Primate ◽

Nonhuman Primates ◽

Rhesus Macaques ◽

Host Immune System ◽

Primate Model ◽

Acute Hiv Infection ◽

Natural Hosts ◽

Siv Infection ◽

Lentiviral Infections

Abstract The host immune system is profoundly affected during the acute phase of progressive immunodeficiency lentiviral infections. Studies of these alterations have been quite restricted in humans because of the limited availability of samples from acutely HIV-infected persons. Therefore, numerous studies have turned attention to nonhuman primate models. Specifically, SIV-infected rhesus macaques (RMs) have been informative for understanding the pathogenesis of HIV infection in humans. Indeed, advantages of the nonhuman primate model include the ability to study the very early events after infection and the ability to retrieve copious amounts of tissues. In addition, nonhuman primates allow for comparative studies between non-natural and natural hosts for SIV, in which SIV infection results in progression, or not, to AIDS, respectively. Although SIV infection of RM is the best model for HIV infection, the immunologic and/or virologic phenomena in SIV-infected RM do not always reflect those seen in HIV-infected humans. Here virologic and immunologic aspects of acute HIV infection of humans and SIV infection of Asian and African nonhuman primates are discussed and compared in relation to how these aspects relate to disease progression.

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