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Nonalcoholic fatty liver disease or NAFLD is a complex and multifactorial liver disease that is affecting a majority of the world’s population now more than ever. The review focuses on two major contributing factors in the etiology of the disease – oxidative stress and the gut microbiota. There is a complex interplay between oxidative stress and the gut microbiota in the pathogenesis of NAFLD. Oxidative stress in NAFLD can result from both the accumulation of lipids in the liver and the interactions between gut-derived metabolites and the liver. Dysbiosis in the gut microbiota can contribute to oxidative stress by promoting the production of reactive oxygen species and altering the balance of antioxidant systems. This interplay between oxidative stress and the gut microbiota can create a vicious cycle, where dysbiosis contributes to oxidative stress, and oxidative stress further promotes dysbiosis, exacerbating liver damage in NAFLD. Understanding the intricate relationship between oxidative stress, the gut microbiota, and NAFLD is essential for developing targeted therapeutic strategies. In this context, more scientific research is required to unravel the complex and interconnecting pathways underlying NAFLD pathogenesis and progression. Modulating the gut microbiota through dietary interventions, prebiotics, probiotics, and change in lifestyle may help restore microbial balance and reduce oxidative stress in NAFLD.

Background: During the early postnatal life, gut microbiota development experiences dynamic changes in their structural and functional composition. The postnatal period is the critical window to develop a host defense mechanism. The maturation of intestinal mucosal barrier integrity is one of the essential defense mechanisms to prevent the entry of pathogens. However, the co-development of intestinal microbial colonization, formation of barrier integrity, and intestinal epithelial cell layer is not entirely understood. Methods: We studied the gut microbial composition and diversity using 16S rRNA marker gene-based sequencing in mice to understand postnatal age-dependent association kinetics between gut microbial and intestinal development. Next, we assessed the intestinal development by in vivo gut permeability assay, mRNA gene expression of different tight junction proteins and intestinal epithelial cell markers, goblet cells population, villus length, and cecal IgA quantification. Results: Our results showed a significant shift in gut microbial structural and functional composition from postnatal day 14 onwards with early life Proteobacteria abundance. Relative abundance of Verrucomicrobia was maximum at postnatal day 14 and showed a gradual decrease over time. We also observed an age-dependent biphasic pattern in barrier integrity improvement and differentiation of intestinal epithelial cells (IECs). A significant improvement in barrier integrity between days 1 and 7 showed the host factor contribution, while that beyond day 14 revealed an association with changes in microbiota composition. Our temporal correlation analysis associated Bacteroidetes phylum with the mucosal barrier formation during postnatal development. Conclusions: The present study revealed the importance and interplay of host factors and the microbiome in gut development and intestinal mucosal homeostasis.

Microbiome studies are quickly gaining momentum. Since most of the resident microbes (consisting of bacteria, fungi, and viruses) are difficult to culture, sequencing the microbial genome is the method of choice to characterize them. It is therefore important to have efficient methodology for gDNA isolation of gut microbes. Mouse models are widely used to understand human disease etiology while avoiding human ethics-related complications. However, the widely used kit-based methods are costly, and sometimes yields (in terms of quality and quantity) are sub-optimal. To overcome this problem, we developed a straightforward, standardized DNA isolation procedure from mouse cecal content for further microbiome-related studies. The reagents we used to standardize the procedure are readily available even in a not-so-well-equipped laboratory, and the reagents are not expensive. The yield and quality of the DNA are also better than those obtained by the readily available kit-based methods.Additionally, we modified the kit-based method of RNA isolation from the colon tissue sample of the mouse for better yield. Churning the tissue with liquid nitrogen at the beginning of the procedure improves RNA quality and quantity.Graphical abstract:

Obesity is a complex health condition that increases the susceptibility to developing cardiovascular diseases, diabetes, and numerous other metabolic health issues. The effect of obesity is not just limited to the conditions mentioned above; it is also seen to have a profound impact on the patient’s mental state, leading to the onset of various mental disorders, particularly mood disorders. Therefore, it is necessary to understand the mechanism underlying the crosstalk between obesity and mental disorders. The gut microbiota is vital in regulating and maintaining host physiology, including metabolism and neuronal circuits. Because of this newly developed understanding of gut microbiota role, here we evaluated the published diverse information to summarize the achievement in the field. In this review, we gave an overview of the association between obesity, mental disorders, and the role of gut microbiota there. Further new guidelines and experimental tools are necessary to understand the microbial contribution to regulate a balanced healthy life.

The health and economic burden of colitis is increasing globally. Understanding the role of host genetics and metagenomics is essential to establish the molecular basis of colitis pathogenesis. In the present study, we have used a common composite dose of DSS to compare the differential disease severity response in C57BL/6 (Th1 biased) and BALB/c (Th2 biased) mice with zero mortality rates. We employed multi-omics approaches and developed a newer vector analysis approach to understand the molecular basis of the disease pathogenesis. In the current report, comparative transcriptomics, metabonomics, and metagenomics analyses revealed that the Th1 background of C57BL/6 induced intense inflammatory responses throughout the treatment period. On the contrary, the Th2 background of BALB/c resisted severe inflammatory responses by modulating the host’s inflammatory, metabolic, and gut microbial profile. The multi-omics approach also helped us discover some unique metabolic and microbial markers associated with the disease severity. These biomarkers could be used in diagnostics.

Probiotics are functional foods and are becoming more evident with time that probiotics can have prophylactic and therapeutic roles. Current report revealed that an established probiotic cocktail of Lactobacillus delbruckei sp. bulgaricus DWT1 and Streptococcus thermophilus DWT4, could inhibit tumor growth. This probiotic cocktail is already marketed in various forms of food supplement. Present report reveals the transition of M2 to M1 like state of macrophage cells of mouse origin in vitro, ex vivo and in vivo following treatment with the established probiotic cocktail. Current study for the first time suggests the ability of a probiotic formulation to polarize macrophages from M2 to M1 state with potentials of developing newer intervention strategies for tumor growth. As a validation of our claim, we have established a novel and significant way of tumor inhibition in mouse model by the probiotic formulation that is capable of polarizing macrophages from M2 to M1.

Abstract Background Antimicrobial peptides (AMPs) have the potential to serve as an alternative to antibiotic. AMPs usually exert bactericidal activity via direct killing of microbial pathogens. Reports have proposed that by harnessing innate immune activation, AMPs can regulate pathogen invasion and may control infection. It has been reported that AMPs could be utilized to activate the innate mucosal immune response in order to eliminate pathogenic infections. This way of controlling pathogen infection, by activating host immunity, confers the potential to the select AMPs to alleviate the problem of antibiotic resistance. Among various AMPs tested LL-37 and indolicidin, showed promise to be potential candidates for eliciting enhanced host innate immune responses. LL-37 and indolicidin had exhibited substantial innate immune activation in both human and murine macrophages. Dosage for each of the AMPs, however, was high with adverse side effects. Results In this study, we reported that upon conjugation with carbon nanotubes (CNT), each AMP remained biologically functional at a concentration that was 1000-fold less than the dosage required for free AMP to remain active in the cells. Conclusions Current study also revealed that while indolicidin induced signalling events mediated through the TNFRSF1A pathway in THP1 cells, followed by activation of NFκB and c-JUN pathways, treatment of cells with LL-37 induced signalling events by activating IL1R, with subsequent activation of NFκB and NFAT2. Thp1 cells, primed with CNT conjugated LL-37 or indolicidin, are protected against Salmonella typhimurium infection at 16 h post challenge.

Regulation of adipogenesis, the root cause for obesity, is very poorly understood. However, studies have presented evidence of immuno-metabolic regulation of adipose tissue during periods of chronic psychological stress, leading to adverse conditions related to stress manifestation, including visceral obesity and atherosclerosis. Despite pronounced association of hormonal markers of stress with dys-regulated metabolic states, the contributing signalling events are yet to be established. It is apparent that to understand contributing signalling events we need a model. Although an in vivo model is preferred, it is difficult to establish. The current report, therefore, presents an in vitro model system for the simulation of adipose tissue in a chronic stress micro-environment by growing pre-adipocytes with macrophages in the presence and absence of stress hormones. In this report, effects of cortisol and serotonin on the kinetics of immune and metabolic changes in adipocytes and macrophage (alone and co-cultured) was studied through whole genome transcriptome profiling. A transition from pro- to anti-inflammatory response in the immune profile of pre-adipocytes, with increasing time in co-culture with macrophages, was observed. This transition was reversed by stress hormones cortisol and/or serotonin.

Palok Aich, Andrew A Potter, Philip J GriebelVaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, CanadaAbstract: Studies in animals and humans link both physical and psychological stress with an increased incidence and severity of respiratory infections. For this manuscript we define stress as the physiological responses an individual undergoes while adjusting to a continually changing environment. It is known that stressors of various types (psychological/physical) can alter the physiological levels of certain hormones, chemokines and cytokines. These alterations send information to the central nervous system to take necessary action which then sends messages to appropriate organs/tissues/cells to respond. These messages can either activate or suppress the immune system as needed and failure to compensate for this by the body can lead to serious health-related problems. Little is known how stress affects disease susceptibility, yet understanding this mechanism is important for developing effective treatments, and for improving health and food quality. The current review focuses on (a) the effects of psychological stressors in humans and animals, (b) various methodologies employed to understand stress responses and their outcomes, and (c) the current status of the attempts to correlate stress and disease with respiratory disease as model system. The methodologies included in this review span traditional epidemiological, behavioral and immunological studies to current high throughput genomic, proteomic, metabolomic/metabonomic approaches. With the advent of various newer omics and bioinformatics methodologies we postulate that it will become feasible to understand the mechanisms through which stress can influence disease onset. Although the literature in this area is limited because of the infancy of this research area, the objective of this review is to illustrate the power of new approaches to address complex biological questions. These new approaches will also aid in our understanding how these processes are related to the dynamics and kinetics of changes in expression of multiple genes at various levels.Keywords: stress, disease, biomarker discovery, systems biology, omics, respiratory disease

Antibiotic resistance is concern of today's world. Search for alternative molecules, for treatment and immune stimulation, remains at the forefront. One such group of biomolecules with promise, along the line of immune stimulation or therapy, is host defense peptide (HDP). These molecules, however, are required at a higher dose to be effective which leads to high cost. To alleviate such problems, an aid can be used to achieve similar efficacy but at a smaller effective dose of the immune stimulant. We hypothesised that by conjugating HDPs with carbon nanotubes and/or gold nanoparticles, it would be possible to stimulate a protective immune response in host system at a lower dosage of HDP. In this report, we characterized, using biophysical methodologies, conjugation of Indolicidin, as a representative of HDP. We further established efficacy of peptide-nanomaterial conjugates in activating innate immunity and protecting against pathogen infection in vitro at a significantly small dose.

Stress has long been known to increase susceptibility to health disorders. In 2009, American Psychological Association further established association of stress to serious health problems. However, a quantitative and accurate way to evaluate and estimate stress status of individuals is still a big challenge. It has been shown, in large animal models using cattle, that psychological stress can be quantified as well as disease susceptibility could be predicted through biomarker discovery. Taking cue from those studies, we have evaluated and estimated psychological stress level of individuals theoretically and validated experimentally. Various biomarkers have also been identified which can be associated to psychological stress to predict stress status of unknown individuals.

Stress is perhaps easiest to conceptualize as a process which allows an organism to accommodate for the demands of its environment such that it can adapt to the prevailing set of conditions. Psychological stress is an important component with the potential to affect physiology adversely as has become evident from various studies in the area. Although these studies have established numerous effects of psychological stress on physiology, a global strategy for the correlation of these effects has yet to begin. Our comparative and systematic analysis of the published literature has unraveled certain interesting molecular mechanisms as clues to account for some of the observed effects of psychological stress on human physiology. In this study, we attempt to understand initial phase of the physiological response to psychological stress by analyzing interactions between innate immunity and metabolism at systems level by analyzing the data available in the literature. In light of our gene association-networks and enrichment analysis we have identified candidate genes and molecular systems which might have some associative role in affecting psychological stress response system or even producing some of the observed terminal effects (such as the associated physiological disorders). In addition to the already accepted role of psychological stress as a perturbation that can disrupt physiological homeostasis, we speculate that it is potentially capable of causing deviation of certain biological processes from their basal level activity after which they can return back to their basal tones once the effects of stress diminish. Based on the derived inferences of our comparative analysis, we have proposed a probabilistic mechanism for how psychological stress could affect physiology such that these adaptive deviations are sometimes not able to bounce back to their original basal tones, and thus increase physiological susceptibility to metabolic and immune imbalance.

AbstractFatal bovine respiratory disease (BRD) is frequently the result of a primary viral and a secondary bacterial respiratory infection. In cattle, BRD causes more than half of feedlot deaths and has a major impact on financial losses in the cattle industry in North America. It is, therefore, very important to understand the mechanism of this complex disease process as well to predict and identify BRD susceptible cattle to enhance treatment efficacy. We recently established the value of using combinatorial omics approaches to identify candidate biomarkers associated with stress responses, a factor that can increase the severity of BRD. The objective of the present investigation was to experimentally recreate fatal BRD and to use a combinatorial analysis of proteomic, metabonomic, and elemental profiles in serum samples to determine if multimethod analysis of these biomarkers could predict disease outcome. The proteomic studies revealed that changes in the serum proteome were significant on day 4 postviral infection when compared to preinfection (day 0) serum samples. Proteomic studies identified a group of acute phase proteins (haptoglobin and apolipoprotein AI), which could be linked to a primary viral respiratory infection, but there was no significant association observed with fatal BRD. In contrast, metabonomic and elemental analyses identified candidate biomarkers for viral infection (glucose, LDL, valine, phosphorous, and iron) and disease outcome (lactate, glucose, iron). While multivariate analysis of proteomic and metabolite profiles did not discriminate between animals that survived or died postsynergic viral–bacterial infection by analyzing preinfection (day 0) serum samples, analysis of serum elemental profiles prior to infection was, however, predictive of BRD outcome. Furthermore, discriminant analyses of all three methodologies used to profile serum (collected on day 4 postviral but prior to bacterial infection) revealed differential trends between animals that survived or died following synergic viral–bacterial infection. Thus, a combinatorial approach using proteomic, metabonomic, and elemental analyses of serum samples revealed that multimethod analysis could discriminate between the complex biological responses to secondary bacterial respiratory infection and predict disease outcome. [ABSTRACT FROM AUTHOR]

Fatal bovine respiratory disease (BRD) is a major cause of financial losses in the cattle industry. A variety of stressors have been implicated as contributing to disease severity. However, it has proven difficult to determine the role these individual factors may play in the final outcome of this disease complex. The objective of the present investigation was to obtain proteomic, metabonomic, and elemental profiles of bovine serum samples from stressed and control animals before and after a primary viral infection to determine if these profiles could distinguish between responses to stressors and viral infection. Multivariate analysis revealed distinct differential trends in the distribution profile of proteins, metabolites, and elements following a stress response both before and after primary viral infection. A group of acute phase proteins, metabolites, and elements could be specifically linked to either a stress response (decreased serum amyloid A and Cu, increased apolipoprotein CIII, amino acids, LDL, P, and Mo) or a primary viral respiratory infection (increased apolipoprotein A1, haptoglobin, glucose, amino acids, LDL and Cu, decreased Lipid, and P). Thus, combined OMICS analysis of serum samples revealed that multimethod analysis could be used to discriminate between the complex biological responses to stress and viral infection. [ABSTRACT FROM AUTHOR]