Host Physiological Parameters Research Articles

Insights of Host Physiological Parameters and Gut Microbiome of Indian Type 2 Diabetic Patients Visualized via Metagenomics and Machine Learning Approaches.

Type 2 diabetes (T2D) is a serious public health issue and may also contribute to modification in the structure of the intestinal microbiota, implying a link between T2D and microbial inhabitants in the digestive tract. This work aimed to develop efficient models for identifying essential physiological markers for improved T2D classification using machine learning algorithms. Using amplicon metagenomic approaches, an effort has also been made to understand the alterations in core gut microbial members in Indian T2D patients with respect to their control normal glucose tolerance (NGT). Our data indicate the level of fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) were the most useful physiological indicators while random forest and support vector machine with RBF Kernel were effective predictions models for identifications of T2D. The dominating gut microbial members Allopreotella, Rikenellaceae RC9 gut group, Haemophilus, Ruminococcus torques group, etc. in Indian T2D patients showed a strong association with both FBG and HbA1c. These members have been reported to have a crucial role in gut barrier breakdown, blood glucose, and lipopolysaccharide level escalation, or as biomarkers. While the dominant NGT microbiota (Akkermansia, Ligilactobacillus, Enterobacter, etc.) in the colon has been shown to influence inflammatory immune responses by acting as an anti-inflammatory agent and maintaining the gut barrier. The topology study of co-occurrence network analysis indicates that changes in network complexity in T2D lead to variations in the different gut microbial members compared to NGT. These studies provide a better understanding of the gut microbial diversity in Indian T2D patients and show the way for the development of valuable diagnostics strategies to improve the prediction and modulation of the T2D along with already established methods.

Identification of a brainstem locus that inhibits tumor necrosis factor

In the brain, compact clusters of neuron cell bodies, termed nuclei, are essential for maintaining parameters of host physiology within a narrow range optimal for health. Neurons residing in the brainstem dorsal motor nucleus (DMN) project in the vagus nerve to communicate with the lungs, liver, gastrointestinal tract, and other organs. Vagus nerve-mediated reflexes also control immune system responses to infection and injury by inhibiting the production of tumor necrosis factor (TNF) and other cytokines in the spleen, although the function of DMN neurons in regulating TNF release is not known. Here, optogenetics and functional mapping reveal cholinergic neurons in the DMN, which project to the celiac-superior mesenteric ganglia, significantly increase splenic nerve activity and inhibit TNF production. Efferent vagus nerve fibers terminating in the celiac-superior mesenteric ganglia form varicose-like structures surrounding individual nerve cell bodies innervating the spleen. Selective optogenetic activation of DMN cholinergic neurons or electrical activation of the cervical vagus nerve evokes action potentials in the splenic nerve. Pharmacological blockade and surgical transection of the vagus nerve inhibit vagus nerve-evoked splenic nerve responses. These results indicate that cholinergic neurons residing in the brainstem DMN control TNF production, revealing a role for brainstem coordination of immunity.

New Insights into the Intrinsic and Extrinsic Factors That Shape the Human Skin Microbiome.

Despite recognition that biogeography and individuality shape the function and composition of the human skin microbiome, we know little about how extrinsic and intrinsic host factors influence its composition. To explore the contributions of these factors to skin microbiome variation, we profiled the bacterial microbiomes of 495 North American subjects (ages, 9 to 78 years) at four skin surfaces plus the oral epithelium using 16S rRNA gene amplicon sequencing. We collected subject metadata, including host physiological parameters, through standardized questionnaires and noninvasive biophysical methods. Using a combination of statistical modeling tools, we found that demographic, lifestyle, and physiological factors collectively explained 12 to 20% of the variability in microbiome composition. The influence of health factors was strongest on the oral microbiome. Associations between host factors and the skin microbiome were generally dominated by operational taxonomic units (OTUs) affiliated with the Clostridiales and Prevotella A subset of the correlations between microbial features and host attributes were site specific. To further explore the relationship between age and the skin microbiome of the forehead, we trained a Random Forest regression model to predict chronological age from microbial features. Age was associated mostly with two mutually coexcluding Corynebacterium OTUs. Furthermore, skin aging variables (wrinkles and hyperpigmented spots) were independently correlated to these taxa.IMPORTANCE Many studies have highlighted the importance of body site and individuality in shaping the composition of the human skin microbiome, but we still have a poor understanding of how extrinsic (e.g., lifestyle) and intrinsic (e.g., age) factors influence its composition. We characterized the bacterial microbiomes of North American volunteers at four skin sites and the mouth. We also collected extensive subject metadata and measured several host physiological parameters. Integration of host and microbial features showed that the skin microbiome was predominantly associated with demographic, lifestyle, and physiological factors. Furthermore, we uncovered reproducible associations between chronological age, skin aging, and members of the genus Corynebacterium Our work provides new understanding of the role of host selection and lifestyle in shaping skin microbiome composition. It also contributes to a more comprehensive appreciation of the factors that drive interindividual skin microbiome variation.

Feed Restriction Modifies Intestinal Microbiota-Host Mucosal Networking in Chickens Divergent in Residual Feed Intake

Differences in chickens' feed intake may be the underlying factor influencing feed-efficiency (FE)-associated variation in intestinal microbiota and physiology. In chickens eating the same amount of feed, quantitative feed restriction may create similar intestinal conditions and help clarify this cause-and-effect relationship. This study investigated the effect of ad libitum versus restrictive feeding (85% of ad libitum) on ileal and cecal microbiota, concentrations of short-chain fatty acids, visceral organ size, intestinal morphology, permeability, and expression of genes related to nutrient uptake, barrier function, and innate immune response in broiler chickens with divergent residual feed intake (RFI; metric for FE). On day 30 posthatch, 28 low-RFI (good FE) and 29 high-RFI (poor FE) chickens across both feeding-level groups (n = 112) were selected. Supervised multigroup data integration and relevance network analyses showed that especially Lactobacillus (negative) in ileal digesta, Turicibacter (positive) in cecal digesta, and Enterobacteriaceae (positive) in both intestinal segments depended on chicken's feed intake, whereas the level of Anaerotruncus in cecal digesta was most discriminative for high RFI. Moreover, shallower crypts and fewer goblet cells in ceca indicated host-related energy-saving mechanisms with low RFI, whereas greater tissue resistance suggested a stronger jejunal barrier function in low-RFI chickens. Values corresponding to feed intake level × RFI interactions indicated larger pancreas and lower levels of ileal and cecal short-chain fatty acids in restrictively fed high-RFI chickens than in the other 3 groups, suggesting host physiological adaptations to support greater energy and nutrient needs of high-RFI chickens compensating for the restricted feeding. IMPORTANCE The impact of the FE-associated differences in feed intake on intestinal bacterial and host physiological parameters has so far not been clarified. Understanding the underlying principles is essential for the development of cost-effective strategies to improve FE in chicken production. Under conditions of quantitative feed restriction, low- and high-RFI chickens ate the same amount of feed. Therefore, this research helps in distinguishing intestinal bacterial taxa and functions that were highly reliant on feed intake from those that were associated with physiological adaptations to RFI-associated differences in host nutritional needs and intestinal nutrient availability. This work provides a background for further research to assess manipulation of the intestinal microbiota, host physiology, and FE in chickens by dietary intervention.

The Microbiome and Tuberculosis: Early Evidence for Cross Talk.

Tuberculosis (TB) is an ancient infectious disease of humans that has been extensively studied both clinically and experimentally. Although susceptibility to Mycobacterium tuberculosis infection is clearly influenced by factors such as nutrition, immune status, and both mycobacterial and host genetics, the variable pathogenesis of TB in infected individuals remains poorly understood. During the past two decades, it has become clear that the microbiota-the trillion organisms that reside at mucosal surfaces within and on the body-can exert a major influence on disease outcome through its effects on host innate and adaptive immune function and metabolism. This new recognition of the potentially pleiotropic participation of the microbiome in immune responses has raised the possibility that the microbiota may influence M. tuberculosis infection and/or disease. Similarly, treatment of TB may alter the healthy steady-state composition and function of the microbiome, possibly affecting treatment outcome in addition to other host physiological parameters. Herein, we review emerging evidence for how the microbiota may influence the transition points in the life cycle of TB infection, including (i) resistance to initial infection, (ii) initial infection to latent tuberculosis (LTBI), (iii) LTBI to reactivated disease, and (iv) treatment to cure. A major goal of this review is to frame questions to guide future scientific and clinical studies in this largely unexplored but increasingly important area of TB research.

Long-range gap junctional signaling controls oncogene-mediated tumorigenesis in Xenopus laevis embryos.

In addition to the immediate microenvironment, long-range signaling may be an important component of cancer. Molecular-genetic analyses have implicated gap junctions—key mediators of cell-cell communication—in carcinogenesis. We recently showed that the resting voltage potential of distant cell groups is a key determinant of metastatic transformation and tumor induction. Here, we show in the Xenopus laevis model that gap junctional communication (GJC) is a modulator of the long-range bioelectric signaling that regulates tumor formation. Genetic disruption of GJC taking place within tumors, within remote host tissues, or between the host and tumors significantly lowers the incidence of tumors induced by KRAS mutations. The most pronounced suppression of tumor incidence was observed upon GJC disruption taking place farther away from oncogene-expressing cells, revealing a role for GJC in distant cells in the control of tumor growth. In contrast, enhanced GJC communication through the overexpression of wild-type connexin Cx26 increased tumor incidence. Our data confirm a role for GJC in tumorigenesis, and reveal that this effect is non-local. Based on these results and on published data on movement of ions through GJs, we present a quantitative model linking the GJC coupling and bioelectrical state of cells to the ability of oncogenes to initiate tumorigenesis. When integrated with data on endogenous bioelectric signaling during left-right patterning, the model predicts differential tumor incidence outcomes depending on the spatial configurations of gap junction paths relative to tumor location and major anatomical body axes. Testing these predictions, we found that the strongest influence of GJ modulation on tumor suppression by hyperpolarization occurred along the embryonic left-right axis. Together, these data reveal new, long-range aspects of cancer control by the host's physiological parameters.

Evaluation of biochemical, hematological and parasitological parameters of protein-deficient hamsters infected with Ancylostoma ceylanicum.

BackgroundHookworms infect millions of people worldwide and can cause severe clinical symptoms in their hosts. Prospective cohort studies in Brazil show high rates of hookworm reinfection in malnourished children compared to well-nourished children, despite previous treatment. Additionally, soil-transmitted helminth (STH) infections can worsen the nutritional status of affected populations. Therefore, this study aims to clarify the effects of host malnutrition during Ancylostoma ceylanicum infection and how this infection affects host physiological parameters using a hamster model.Methodology/Principal FindingsHamsters were divided into four experimental groups: normal diet or low-protein diet (also referred to as “malnourished”) and A. ceylanicum infection or no infection. More severe pathogenesis was observed in the infected malnourished group, as demonstrated by significant decreases in the hemoglobin concentration, erythrocyte number and packed-cell volume compared to the non-infected malnourished group. Greater numbers of adult parasites and eggs were observed in the malnourished group compared to the control group; however, the oviposition rate was lower in the malnourished group. In general, greater values of total lipids were observed in malnourished animals compared to control animals, including lipids excreted in the stool.ConclusionsIn this work, we have demonstrated that animals fed an isocaloric low-protein diet presented more severe pathogenesis when infected with A. ceylanicum. The increased lipid concentration in the liver and blood is related to the conversion of the excess carbohydrate into fatty acids that increase the concentration of triglycerides in general. Triglycerides were excreted in the feces, indicating that infection associated with malnutrition caused a greater loss of these molecules for this group of animals and confirming the hypothesis that both nutrition and infection are responsible for the malabsorption syndrome. Taken together, the results found in this work confirm the hypothesis that the nutritional condition of the host greatly influences the course of the infection.

Adding new dimensions: towards an integrative understanding of HIV-1 spread.

In vitro studies in primary or immortalized cells continue to be used to elucidate the essential principles that govern the interactions between HIV-1 and isolated target cells. However, until recently, substantial technical barriers prevented this information from being efficiently translated to the more complex scenario of HIV-1 spread in the host in vivo, which has limited our understanding of the impact of host physiological parameters on the spread of HIV-1. In this Review, we discuss the recent development of imaging approaches to visualize HIV-1 spread and the adaptation of these approaches to organotypic ex vivo models and animal models. We focus on new concepts, including the mechanisms and in vivo relevance of cell-cell transmission for HIV-1 spread and the function of the HIV-1 pathogenesis factor Nef, which have emerged from the application of these integrative approaches in complex cell systems.

Potential Role of the Bovine Rumen Microbiome in Modulating Milk Composition and Feed Efficiency

Ruminants are completely dependent on their microbiota for feed digestion and consequently, their viability. It is therefore tempting to hypothesize a connection between the composition and abundance of resident rumen bacterial taxa and the physiological parameters of the host. Using a pyrosequencing approach, we characterized the rumen bacterial community composition in 15 dairy cows and their physiological parameters. We analyzed the degree of divergence between the different animals and found that some physiological parameters, such as milk yield and composition, are highly correlated with the abundance of various bacterial members of the rumen microbiome. One apparent finding was a strong correlation between the ratio of the phyla Firmicutes to Bacteroidetes and milk-fat yield. These findings paralleled human studies showing similar trends of increased adiposity with an increase in Bacteroidetes. This correlation remained evident at the genus level, where several genera showed correlations with the animals' physiological parameters. This suggests that the bacterial community has a role in shaping host physiological parameters. A deeper understanding of this process may allow us to modulate the rumen microbiome for better agricultural yield through bacterial community design.