Gut Microbiome and Its Role in Enteric Infections with Microbial Pathogens

IntroductionThe functional consequences of the bacterial gut microbiome for child health are not well understood. Characteristics of the early child gut microbiome may influence the course of enteric infections, and enteric infections may change the composition of the gut microbiome, all of which may have long-term implications for child growth and development.Methods and analysisWe are conducting a community-based birth cohort study to examine interactions between gut microbiome conditions and enteric infections, and how environmental conditions affect the development of the gut microbiome. We will follow 360 newborns from 3 sites along a rural–urban gradient in northern coastal Ecuador, characterising enteric infections and gut microbial communities in the children every 3 to 6 months over their first 2 years of life. We will use longitudinal regression models to assess the correlation between environmental conditions and gut microbiome diversity and presence of specific taxa, controlling for factors that are known to be associated with the gut microbiome, such as diet. From 6 to 12 months of age, we will collect weekly stool samples to compare microbiome conditions in diarrhoea stools versus stools from healthy children prior to, during and after acute enteric infections, using principal-coordinate analysis and other multivariate statistical methods.Ethics and disseminationEthics approvals have been obtained from Emory University and the Universidad San Francisco de Quito institutional review boards. The findings will be disseminated through conference presentations and peer-reviewed journals.

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Gut Microbiome in Inflammation and Chronic Enteric Infections

Gut Microbiome and Its Impact on Health and Diseases ◽

10.1007/978-3-030-47384-6_6 ◽

2020 ◽

pp. 133-152

Author(s):

Arpita Aditya ◽

Catherine Galleher ◽

Yeal Ad ◽

Mitchell Coburn ◽

Aaron Zweig

Keyword(s):

Gut Microbiome ◽

Enteric Infections

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Nonclinical Safety Assessment of SYN-004

International Journal of Toxicology ◽

10.1177/1091581815623236 ◽

2015 ◽

Vol 35 (3) ◽

pp. 309-316 ◽

Cited By ~ 12

Author(s):

John F. Kokai-Kun ◽

J. Andrew Bristol ◽

John Setser ◽

Michael Schlosser

Keyword(s):

Clinical Trials ◽

Gut Microbiome ◽

Maximum Tolerated Dose ◽

Systemic Absorption ◽

High Dose ◽

Noticeable Effect ◽

Adverse Effect Level ◽

Enteric Infections ◽

Good Laboratory ◽

Effect Level

SYN-004 is a first in class, recombinant β-lactamase that degrades β-lactam antibiotics and has been formulated to be administered orally to patients receiving intravenous β-lactam antibiotics including cephalosporins. SYN-004 is intended to degrade unmetabolized antibiotics excreted into the intestines and thus has the potential to protect the gut microbiome from disruption by these antibiotics. Protection of the gut microbiome is expected to protect against opportunistic enteric infections such as Clostridium difficile infection as well as antibiotic-associated diarrhea. In order to demonstrate that oral SYN-004 is safe for human clinical trials, 2 Good Laboratory Practice-compliant toxicity studies were conducted in Beagle dogs. In both studies, SYN-004 was administered orally 3 times per day up to the maximum tolerated dose of the formulation. In the first study, doses of SYN-004 administered over 28 days were safe and well tolerated in dogs with the no-observed-adverse-effect level at the high dose of 57 mg/kg/day. Systemic absorption of SYN-004 was minimal and sporadic and showed no accumulation during the study. In the second study, doses up to 57 mg/kg/day were administered to dogs in combination with an intravenous dose of ceftriaxone (300 mg/kg) given once per day for 14 days. Coadministration of oral SYN-004 with intravenous ceftriaxone was safe and well tolerated, with SYN-004 having no noticeable effect on the plasma pharmacokinetics of ceftriaxone. These preclinical studies demonstrate that SYN-004 is well tolerated and, when coadministered with ceftriaxone, does not interfere with its systemic pharmacokinetics. These data supported advancing SYN-004 into human clinical trials.

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Significance of the Gut Microbiome for Viral Diarrheal and Extra-Intestinal Diseases

Viruses ◽

10.3390/v13081601 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1601

Author(s):

Ulrich Desselberger

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Neurological Diseases ◽

Bacterial Species ◽

Future Research ◽

Clostridioides Difficile ◽

Host Diet ◽

Enteric Infections ◽

Childhood Vaccines ◽

Definition Of

The composition of the mammalian gut microbiome is very important for the health and disease of the host. Significant correlations of particular gut microbiota with host immune responsiveness and various infectious and noninfectious host conditions, such as chronic enteric infections, type 2 diabetes, obesity, asthma, and neurological diseases, have been uncovered. Recently, research has moved on to exploring the causalities of such relationships. The metabolites of gut microbiota and those of the host are considered in a ‘holobiontic’ way. It turns out that the host’s diet is a major determinant of the composition of the gut microbiome and its metabolites. Animal models of bacterial and viral intestinal infections have been developed to explore the interrelationships of diet, gut microbiome, and health/disease phenotypes of the host. Dietary fibers can act as prebiotics, and certain bacterial species support the host’s wellbeing as probiotics. In cases of Clostridioides difficile-associated antibiotic-resistant chronic diarrhea, transplantation of fecal microbiomes has sometimes cured the disease. Future research will concentrate on the definition of microbial/host/diet interrelationships which will inform rationales for improving host conditions, in particular in relation to optimization of immune responses to childhood vaccines.

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Gut Microbiome Changes with Acute Diarrheal Disease in Urban Versus Rural Settings in Northern Ecuador

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.20-0831 ◽

2021 ◽

Author(s):

Maria J. Soto-Girón ◽

Angela Peña-Gonzalez ◽

Janet K. Hatt ◽

Lorena Montero ◽

Maritza Páez ◽

...

Keyword(s):

Gut Microbiome ◽

Urban Areas ◽

Diarrheal Disease ◽

Rural Populations ◽

Urban Populations ◽

Rural And Urban Areas ◽

Rural And Urban ◽

Rural Settings ◽

Enteric Infections ◽

Rural Sites

Previous studies have reported lower fecal bacterial diversity in urban populations compared with those living in rural settings. However, most of these studies compare geographically distant populations from different countries and even continents. The extent of differences in the gut microbiome in adjacent rural versus urban populations, and the role of such differences, if any, during enteric infections remain poorly understood. To provide new insights into these issues, we sampled the gut microbiome of young children with and without acute diarrheal disease (ADD) living in rural and urban areas in northern Ecuador. Shotgun metagenomic analyses of non-ADD samples revealed small but significant differences in the abundance of microbial taxa, including a greater abundance of Prevotella and a lower abundance of Bacteroides and Alistipes in rural populations. Greater and more significant shifts in taxon abundance, metabolic pathway abundance, and diversity were observed between ADD and non-ADD status when comparing urban to rural sites (Welch’s t-test, P < 0.05). Collectively our data show substantial functional, diversity, and taxonomic shifts in the gut microbiome of urban populations with, ADD supporting the idea that the microbiome of rural populations may be more resilient to ADD episodes.

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Folate and vitamin B-12 deficiencies additively impaired memory function and disturbed the gut microbiota in amyloid-β infused rats

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000624 ◽

2019 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Sunmin Park ◽

Sunna Kang ◽

Da Sol Kim

Keyword(s):

Insulin Resistance ◽

Gut Microbiota ◽

Insulin Signaling ◽

Gut Microbiome ◽

Metabolic Diseases ◽

Memory Function ◽

Amyloid Β ◽

Impaired Memory ◽

Ca1 Region ◽

Folate And Vitamin B12

Abstract. Folate and vitamin B12(V-B12) deficiencies are associated with metabolic diseases that may impair memory function. We hypothesized that folate and V-B12 may differently alter mild cognitive impairment, glucose metabolism, and inflammation by modulating the gut microbiome in rats with Alzheimer’s disease (AD)-like dementia. The hypothesis was examined in hippocampal amyloid-β infused rats, and its mechanism was explored. Rats that received an amyloid-β(25–35) infusion into the CA1 region of the hippocampus were fed either control(2.5 mg folate plus 25 μg V-B12/kg diet; AD-CON, n = 10), no folate(0 folate plus 25 μg V-B12/kg diet; AD-FA, n = 10), no V-B12(2.5 mg folate plus 0 μg V-B12/kg diet; AD-V-B12, n = 10), or no folate plus no V-B12(0 mg folate plus 0 μg V-B12/kg diet; AD-FAB12, n = 10) in high-fat diets for 8 weeks. AD-FA and AD-VB12 exacerbated bone mineral loss in the lumbar spine and femur whereas AD-FA lowered lean body mass in the hip compared to AD-CON(P < 0.05). Only AD-FAB12 exacerbated memory impairment by 1.3 and 1.4 folds, respectively, as measured by passive avoidance and water maze tests, compared to AD-CON(P < 0.01). Hippocampal insulin signaling and neuroinflammation were attenuated in AD-CON compared to Non-AD-CON. AD-FAB12 impaired the signaling (pAkt→pGSK-3β) and serum TNF-α and IL-1β levels the most among all groups. AD-CON decreased glucose tolerance by increasing insulin resistance compared to Non-AD-CON. AD-VB12 and AD-FAB12 increased insulin resistance by 1.2 and 1.3 folds, respectively, compared to the AD-CON. AD-CON and Non-AD-CON had a separate communities of gut microbiota. The relative counts of Bacteroidia were lower and those of Clostridia were higher in AD-CON than Non-AD-CON. AD-FA, but not V-B12, separated the gut microbiome community compared to AD-CON and AD-VB12(P = 0.009). In conclusion, folate and B-12 deficiencies impaired memory function by impairing hippocampal insulin signaling and gut microbiota in AD rats.

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