Feasibility of fecal microbiota transplantation via oral gavage to safely alter gut microbiome composition in marmosets

Disruption of microbial communities within human hosts has been associated with infection, obesity, cognitive decline, cancer risk and frailty, suggesting that microbiome-targeted therapies may be an option for improving healthspan and lifespan. The objectives of this study were to determine the feasibility of delivering fecal microbiota transplants (FMTs) to marmosets via oral gavage and to evaluate if alteration of the gut microbiome post-FMT could be achieved. This was a prospective study of marmosets housed at the Barshop Institute for Longevity and Aging Studies in San Antonio, Texas. Eligible animals included healthy young adult males (age 2–5 years) with no recent medication use. Stool from two donors was combined and administered in 0.5 ml doses to five young recipients once weekly for 3 weeks. Safety outcomes and alterations in the gut microbiome composition via 16S ribosomal RNA sequencing were compared at baseline and monthly up to 6 months post-FMT. Overall, significant differences in the percent relative abundance was seen in FMT recipients at the phylum and family levels from baseline to 1 month and baseline to 6 months post-FMT. In permutational multivariate analysis of variance analyses, treatment status (donor vs. recipient) (p = .056) and time course (p = .019) predicted β diversity (p = .056). The FMT recipients did not experience any negative health outcomes over the course of the treatment. FMT via oral gavage was safe to administer to young adult marmosets. The marmoset microbiome may be altered by FMT; however, progressive changes in the microbiome are strongly driven by the host and its baseline microbiome composition.     

Distribution and morphology of ghrelin immunostained cells in the adrenal gland of the African ostrich

Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor. We investigated the distribution and morphological characteristics of ghrelin-immunopositive (ghrelin-ip) cells in the African ostrich adrenal gland. We found that the adrenal gland of the African ostrich consisted of three parts: capsule, inter-renal tissue and chromaffin cells. The inter-renal tissue and chromaffin cells interdigitated irregularly. The inter-renal tissue consisted of a peripheral zone and a central inner zone. The peripheral zone could be divided into an outer subcapsular zone and an inner zone. The subcapsular zone cells were arranged as a bow, while the inner area cells formed cords that were perpendicular to the capsule. The central inner zone exhibited irregular clumps and the cells were morphologically similar to chromaffin cells. Ghrelin-ip cells were located throughout the adrenal gland except the capsule. The majority of ghrelin-ip cells were found among the chromaffin cells. The number of ghrelin-ip cells in the inter-renal tissue decreased gradually from the central inner zone, to the inner zone to the subcapsular zone. The ghrelin-ip cells were oval or irregular in shape and exhibited cytoplasmic staining. Our findings suggest that ghrelin may play a role in regulating adrenal hormone secretion in the African ostrich.     

Comparative Value of Four Measures of Retention in Expert Care in Predicting Clinical Outcomes and Health Care Utilization in HIV Patients

This study compared the ability of four measures of patient retention in HIV expert care to predict clinical outcomes. This retrospective study examined Veterans Health Administration (VHA) beneficiaries with HIV (ICD-9-CM codes 042 or V08) receiving expert care (defined as HIV-1 RNA viral load and CD4 cell count tests occurring within one week of each other) at VHA facilities from October 1, 2006, to September 30, 2008. Patients were ≥18 years old and continuous VHA users for at least 24 months after entry into expert care. Retention measures included: Annual Appointments (≥2 appointments annually at least 60 days apart), Missed Appointments (missed ≥25% of appointments), Infrequent Appointments (>6 months without an appointment), and Missed or Infrequent Appointments (missed ≥25% of appointments or >6 months without an appointment). Multivariable nominal logistic regression models were used to determine associations between retention measures and outcomes. Overall, 8,845 patients met study criteria. At baseline, 64% of patients were virologically suppressed and 37% had a CD4 cell count >500 cells/mm³. At 24 months, 82% were virologically suppressed and 46% had a CD4 cell count >500 cells/mm³. During follow-up, 13% progressed to AIDS, 48% visited the emergency department (ED), 28% were hospitalized, and 0.3% died. All four retention measures were associated with virologic suppression and antiretroviral therapy initiation at 24 months follow-up. Annual Appointments correlated positively with CD4 cell count >500 cells/mm³. Missed Appointments was predictive of all primary and secondary outcomes, including CD4 cell count ≤500 cells/mm³, progression to AIDS, ED visit, and hospitalization. Missed Appointments was the only measure to predict all primary and secondary outcomes. This finding could be useful to health care providers and public health organizations as they seek ways to optimize the health of HIV patients.     

Age‐related changes in the marmoset gut microbiome

The gut microbiome is known to play a significant role in human health but its role in aging remains unclear. The objective of this study was to compare the gut microbiome composition between young adult and geriatric non‐human primates (marmosets) as a model of human health and disease. Stool samples were collected from geriatric (8+ years) and young adult males (2–5 years). Stool 16S ribosomal RNA V4 sequences were amplified and sequenced on the Illumina MiSeq platform. Sequences were clustered into operational taxonomic units and classified via Mothur's Bayesian classifier referenced against the Greengenes database. A total of 10 young adult and 10 geriatric marmosets were included. Geriatric marmosets had a lower mean Shannon diversity compared with young marmosets (3.15 vs. 3.46; p = 0.0191). Geriatric marmosets had a significantly higher mean abundance of Proteobacteria (0.22 vs. 0.09; p = 0.0233) and lower abundance of Firmicutes (0.15 vs. 0.19; p = 0.0032) compared with young marmosets. Geriatric marmosets had a significantly higher abundance of Succinivibrionaceae (0.16 vs. 0.01; p = 0.0191) and lower abundance of Porphyromonadaceae (0.07 vs. 0.11; p = 0.0494). In summary, geriatric marmosets had significantly altered microbiome diversity and composition compared with young adult marmosets. Further studies are needed to test microbiome‐targeted therapies to improve healthspan and lifespan.     

Candidatus Phytoplasma trifolii (16SrVI) infection modifies the polyphenols concentration in pepper (Capsicum annuum) plant tissues

Of late, the presence of Candidatus Phytoplasma trifolii was reported as a serious threat to the pepper crop in Zacatecas, México; therefore, asymptomatic and symptomatic pepper plants were collected from a commercial field among three samplings after the fruit set stage was reached. Total DNA was extracted using the CTAB‐based method and tested for phytoplasma using a nested PCR assay, followed by a BLAST, and restriction fragment length polymorphism (RFLP) analysis of 16S rDNA sequences, which confirmed the presence of phytoplasma group 16SrVI, “Candidatus Phytoplasma trifolii” in the symptomatic plants. As the metabolic pathways of pathogen‐infected plants tend to change, resulting in a biochemical differentiation with the noninfected plants, the polyphenolic compound concentrations were quantified from the vegetative tissues (root, stem, leaves and developed fruit/big bud) and were analysed based on a principal component analysis (PCA). Results revealed that, in general, plants tend to a progressive increase in total phenols, flavonoids, condensed tannins and anthocyanins related to the plants exposure to “Ca. P. trifolii” infection, and PCA demonstrated that almost 90% of the observed variance was explained by the first two components. Hence, the phenolic content of the plants increases as a response of the defence mechanism, which reflects its condition and resistance.     

Haplosufficiency of the melanocortin-4 receptor gene in individuals with deletions of 18q

The melanocortin-4 receptor (MC4R) is a seven, transmembrane G-protein-coupled receptor whose ligand, alpha-melanocyte-stimulating hormone (alpha-MSH), is a post-translational derivative of pro-opiomelanocortin (POMC). The regulatory pathway, of which MC4R is a part, has become an area of intense interest because of its potential role in obesity. Three studies have identified individuals with dominantly inherited obesity segregating with mutations in the MC4R gene. It has been hypothesized that the mutation found in these subjects resulted in a loss of gene function resulting in obesity due to haploinsufficiency of the MC4R gene. We have been studying the molecular basis of the phenotype of individuals with large deletions of chromosome 18q. Due to its location at 18q21.3, the MC4R gene is hemizygous in approximately one-third of the individuals in our study. If hemizygosity of the MC4R gene results in haploinsufficiency-induced obesity, then individuals with deletions of 18q whose deletions include the MC4R gene should be obese in comparison with those individuals whose deletion does not include the gene. Our data indicate no difference in obesity among those deleted and not deleted for the gene. This supports the hypothesis that the MC4R gene product is haplosufficient and the involvement of MC4R in obesity may reflect a dominant negative effect.