The intestinal epithelial layer is the chief barricade between the luminal contents and the host. A healthy homeostatic intestinal barrier is pivotal for maintaining gastrointestinal health, which ...impacts the overall health as it safeguards the gut-blood axis and checks gut microbes including potential pathogens from entering into the circulation.
Under healthy milieus, the intestinal barrier is generally very dynamic and effective, with luminal side being heavily infested with a wide variety of gut microbes while the basolateral side remains virtually sterile. However, certain conditions such as abnormal exposure to toxins, drugs, pathogens etc. or a state of hyper-inflammation due to disease conditions may weaken or destabilize the integrity of gut epithelia. A perturbed gut integrity and permeability ("leaky gut") may lead to microbial (bacterial) translocation, and the eventual leakage of bacteria or their metabolites into the circulation can make the host susceptible to various types of diseases via inducing chronic or acute inflammatory response. Key Message: Given a close association with gut integrity, bacterial translocation and inflammatory responses have recently emerged as a clinically important research field and have unveiled novel aspects of gut microbial ecology and various gastrointestinal, metabolic, and lifestyle diseases. This review aims to describe the significance of a healthy gut barrier integrity and permeability, as well as the factors and consequences associated with a compromised gut barrier, while discussing briefly the dietary approaches including probiotics and prebiotics that could ameliorate gut health by restoring gut environment and barrier integrity, thereby preventing bacterial translocation.
In the United States, farm-raised shrimp accounts for ~ 80% of the market share. Farmed shrimp are cultivated as monoculture and are susceptible to infections. The aquaculture industry is dependent ...on the application of antibiotics for disease prevention, resulting in the selection of antibiotic-resistant bacteria. We aimed to characterize the prevalence of antibiotic-resistant bacteria and gut microbiome communities in commercially available shrimp. Thirty-one raw and cooked shrimp samples were purchased from supermarkets in Florida and Georgia (U.S.) between March-September 2019. The samples were processed for the isolation of antibiotic-resistant bacteria, and isolates were characterized using an array of molecular and antibiotic susceptibility tests. Aerobic plate counts of the cooked samples (n = 13) varied from < 25 to 6.2 log CFU/g. Isolates obtained (n = 110) were spread across 18 genera, comprised of coliforms and opportunistic pathogens. Interestingly, isolates from cooked shrimp showed higher resistance towards chloramphenicol (18.6%) and tetracycline (20%), while those from raw shrimp exhibited low levels of resistance towards nalidixic acid (10%) and tetracycline (8.2%). Compared to wild-caught shrimp, the imported farm-raised shrimp harbored distinct gut microbiota communities and a higher prevalence of antibiotic-resistance genes in their gut. The presence of antibiotic-resistant strains in cooked shrimps calls for change in processing for their mitigation.
Alzheimer's disease (AD) is a growing concern for the aging population worldwide. With no current cure or reliable treatments available for AD, prevention is an important and growing area of ...research. A range of lifestyle and dietary patterns have been studied to identify the most effective preventive lifestyle changes against AD and related dementia (ADRD) pathology. Of these, the most studied dietary patterns are the Mediterranean, DASH, MIND, ketogenic, and modified Mediterranean-ketogenic diets. However, there are discrepancies in the reported benefits among studies examining these dietary patterns. We herein compile a narrative/literature review of existing clinical evidence on the association of these patterns with ADRD symptomology and contemplate their preventive/ameliorative effects on ADRD neuropathology in various clinical milieus. By and large, plant-based dietary patterns have been found to be relatively consistently and positively correlated with preventing and reducing the odds of ADRD. These impacts stem not only from the direct impact of specific dietary components within these patterns on the brain but also from indirect effects through decreasing the deleterious effects of ADRD risk factors, such as diabetes, obesity, and cardiovascular diseases. Importantly, other psychosocial factors influence dietary intake, such as the social connection, which may directly influence diet and lifestyle, thereby also impacting ADRD risk. To this end, prospective research on ADRD should include a holistic approach, including psychosocial considerations.
An important yet poorly understood facet of the life cycle of a successful pathogen is host-to-host transmission. Hospital-acquired infections (HAI) resulting from the transmission of drug-resistant ...pathogens affect hundreds of millions of patients worldwide.
, a Gram-negative bacterium, is notorious for causing HAI, with many of these infections difficult to treat, as
has become multidrug resistant. Epidemiological studies suggest that
host-to-host transmission requires close contact and generally occurs through the fecal-oral route. Here, we describe a murine model that can be utilized to study mucosal (oropharynx and gastrointestinal GI) colonization, shedding within feces, and transmission of
through the fecal-oral route. Using an oral route of inoculation, and fecal shedding as a marker for GI colonization, we showed that
can asymptomatically colonize the GI tract in immunocompetent mice and modifies the host GI microbiota. Colonization density within the GI tract and levels of shedding in the feces differed among the clinical isolates tested. A hypervirulent
isolate was able to translocate from the GI tract and cause hepatic infection that mimicked the route of human infection. Expression of the capsule was required for colonization and, in turn, robust shedding. Furthermore,
carrier mice were able to transmit to uninfected cohabitating mice. Lastly, treatment with antibiotics led to changes in the host microbiota and development of a transient supershedder phenotype, which enhanced transmission efficiency. Thus, this model can be used to determine the contribution of host and bacterial factors toward
dissemination.
The gut bacteria producing metabolites like short-chain fatty acids (SCFAs; e.g., acetate, propionate and butyrate), are frequently reduced in Patients with diabetes, obesity, autoimmune disorders, ...and cancers. Hence, microbiome modulators such as probiotics may be helpful in maintaining or even restoring normal gut microbiome composition to benefit host health. Herein, we developed a human-origin probiotic cocktail with the ability to modulate gut microbiota to increase native SCFA production. Following a robust protocol of isolation, characterization and safety validation of infant gut-origin Lactobacillus and Enterococcus strains with probiotic attributes (tolerance to simulated gastric and intestinal conditions, adherence to intestinal epithelial cells, absence of potential virulence genes, cell-surface hydrophobicity, and susceptibility to common antibiotics), we select 10 strains (5 from each genera) out of total 321 isolates. A single dose (oral gavage) as well as 5 consecutive doses of this 10-strain probiotic cocktail in mice modulates gut microbiome and increases SCFA production (particularly propionate and butyrate). Inoculation of these probiotics in human feces also increases SCFA production along with microbiome modulation. Results indicate that human-origin probiotic lactobacilli and enterococci could ameliorate gut microbiome dysbiosis and hence may prove to be a potential therapy for diseases involving reduced SCFAs production in the gut.
Type 2 diabetes (T2D) has become a global epidemic. Although several drugs are available to manage T2D, problems associated with person-to-person variability in drug efficacy and potential ...side-effects remain unresolved. Owing to the emerging role of the gut microbiome in obesity and T2D, the interaction between gut microbes and anti-diabetic drugs and its influence on drugs' functions remains of immediate research interest. On one hand, drugs can manipulate gut microbiome composition and metabolic capacity. Conversely, the metabolic activities of the microbiome and its metabolites can also influence drug metabolism and effects. Hence, understanding this bi-directional drug-microbiome interaction and how it influences the clinical outcomes of antidiabetic drugs can pave the way to develop next-generation strategies to ameliorate diabetes. This review presents evidences demonstrating the putative interactions between anti-diabetic drugs and the gut microbiome, and discusses the potential of microbiome modulators to manipulate drug-microbiome interactions and the drug metabolism.
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•Gut microbes interact with medications used to treat T2D, that at least partially mediates potential benefits of these drugs.•Anti-diabetic drugs impact gut microbiome and its metabolic activity and vice-versa.•Understanding the dynamics of drug-microbiome cross-talk would offer better therapeutic outcomes for diabetes.
The prevalence of type 2 diabetes mellitus (T2D) is increasing worldwide, and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut ...microbiome significantly contribute to the development of T2D, while microbiome modulators may be beneficial for T2D prevention. However, microbiome modulators that are effective, safe, affordable, and able to be administered daily are not yet available. Based on our previous pro- and prebiotic studies, we developed a novel synbiotic yogurt comprised of human-origin probiotics and plant-based prebiotics and investigated its impact on diet- and streptozotocin-induced T2D in mice. We compared the effects of our synbiotic yogurt to those of a commercially available yogurt (control yogurt). Interestingly, we found that the feeding of the synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls. Surprisingly, the control yogurt exacerbated diabetes progression. Synbiotic yogurt beneficially modulated the gut microbiota composition compared to milk, while the control yogurt negatively modulated it by significantly increasing the abundance of detrimental bacteria such as Proteobacteria and
. In addition, the synbiotic yogurt protected pancreatic islet morphology compared to the milk control, while the control yogurt demonstrated worse effects on islets. These results suggest that our newly developed synbiotic yogurt protects against diabetes in mice and can be used as a therapeutic to prevent diabetes progression.
The development of human gut microbiota begins as soon as the neonate leaves the protective environment of the uterus (or maybe
) and is exposed to innumerable microorganisms from the mother as well ...as the surrounding environment. Concurrently, the host responses to these microbes during early life manifest during the development of an otherwise hitherto immature immune system. The human gut microbiome, which comprises an extremely diverse and complex community of microorganisms inhabiting the intestinal tract, keeps on fluctuating during different stages of life. While these deviations are largely natural, inevitable and benign, recent studies show that unsolicited perturbations in gut microbiota configuration could have strong impact on several features of host health and disease. Our microbiota undergoes the most prominent deviations during infancy and old age and, interestingly, our immune health is also in its weakest and most unstable state during these two critical stages of life, indicating that our microbiota and health develop and age hand-in-hand. However, the mechanisms underlying these interactions are only now beginning to be revealed. The present review summarizes the evidences related to the age-associated changes in intestinal microbiota and vice-versa, mechanisms involved in this bi-directional relationship, and the prospective for development of microbiota-based interventions such as probiotics for healthy aging.
Early-life intestinal microbiota development is crucial for host's long-term health and is influenced by many factors including gestational age, birth and feeding modes, birth environment, ...ethnic/geographical background, etc. However, 'quantitative' data on the actual population levels of gut bacterial communities when these influences are controlled for is relatively rare. Herein, we demonstrate a quantitative perspective of microbiota development in natural and healthy milieus, i.e., in healthy, full-term, vaginally born and breast-fed infants (
= 19) born at same clinic. Fecal microbiota at age 1 and 7 days, 1, 3, and 6 months and 3 years is quantified using highly sensitive reverse-transcription-quantitative-PCR assays targeting bacterial rRNA molecules. At day 1, we detect one or more bacteria in all (100%) of the babies, wherein the microbiota is composed mainly of enterobacteria (35%),
group (23%), enterococci (18%), staphylococci (13%), and bifidobacteria (9%). Altogether, facultative anaerobes predominate during first few weeks whereafter obligate anaerobes including bifidobacteria,
group,
group, and
subgroup gradually start prevailing. At 3 years, the composition is represented almost entirely (99%) by obligate anaerobes including
subgroup (34%), bifidobacteria (22%),
group (21%),
group (17%),
cluster (4%), and
(1%). The overall obligate/facultative proportion is 32/68, 37/63, 54/46, 70/30, 64/36, and 99/1% at 1 and 7 days, 1, 3, and 6 months and 3 years, respectively. However, interestingly, considerable individual-specific variations in the obligate/facultative ratios as well as in the proportions of Firmicutes, Bacteroides, Actinobacteria, and Proteobacteria communities are seen among these babies. This disparity even within this highly homogenous cohort manifests the magnitude of diverse patterns of gut microbiota configuration and hence underpins the importance of considering not only the gestational age, birth, and feeding modes, and ethnic/geographical background but also other potential outstanding factors when investigating the elements shaping the early microbiota development. In summary, the data demonstrate a quantitative bird's-eye view of the ontogenesis of early-life gut microbiota in typically natural and healthy milieus and should be informative and facilitative for future studies exploring various aspects of the human gut microbiota.
Oral cavity that harbors diverse bacterial populations could also act as a site of origin for spread of pathogenic microorganisms to different body sites, particularly in immunocompromised hosts, ...patients, the elderly, or the underprivileged. A number of recent publications have advocated that patients with periodontal diseases are more susceptible to metabolic endotoxemia, inflammation, obesity, type 2 diabetes, and other related systemic complications, concluding that periodontal diseases could be a potential contributing risk factor for a wide array of clinically important systemic diseases. However, despite a significant increase in the prevalence of periodontal infections and systemic diseases in the past few decades, the fundamental biological mechanisms of connection between these ailments are still not fully explicated. Consequently, the mechanisms by which this bidirectional damage occurs are being explored with a concentric vision to develop strategies that could prevent or control the complications of these ailments. This paper attempts to summarize and hypothesize the diverse mechanisms that hint to a certain connection between the two prevalent chronic situations.
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