Shalini Jain

• M.Sc., Ph.D.
• Research Associate at Wake Forest University

The microbiome plays a critical role in both promoting human health and contributing to diseases. Multiple emerging evidence shows that it contributes to aging and cognitive decline; however, the mechanisms are not fully understood. Changes in the microbiome and immune system occur with age, and immune functions are one of the key mechanisms linkin...

Background/Objectives: This study evaluates the potential of electroencephalography (EEG) as a noninvasive tool for distinguishing between healthy individuals (n = 79), those with mild cognitive impairment (MCI; n = 36), and dementia patients (n = 7). Methods: Using a 14-channel Emotiv EPOC-X headset, we analyzed power spectral density during a 2-m...

The microbiome and aging: Unlocking new frontiers in healthy longevity Research conducted by the USF Microbiomes Institute and the MiaGB Consortium is uncovering the significant link between microbial communities and host biology. This understanding could lead to new therapies for age-related conditions. Shalini Jain, Christian Brechot, and Hariom...

Microbiome abnormalities (dysbiosis) significantly contribute to the progression of Alzheimer’s disease (AD). However, the therapeutic efficacy of microbiome modulators in protecting against these ailments remains poorly studied. Herein, we tested a cocktail of unique probiotics, including 5 Lactobacillus and 5 Enterococcus strains isolated from in...

Background The microbiota‐immune‐brain axis is implicated in Alzheimer’s disease. Alterations in gut microbiota and immune functions in mild cognitive impairment (MCI) are inconsistent and remain to be understood. This study aims to investigate immune cell phenotyping and its link with gut microbial composition associated with cognitive function....

Background Emerging studies suggest the interaction of the gut microbiome with physical and cognitive function. However, it remains unknown whether the same microbiome is linked with both functions and/or if they are unique. Method Utilizing data and samples from the Microbiome in Aging Gut and Brain (MiaGB) Consortium cohort, we assessed the whol...

Aging population is increasing, leading to a rise in aging-related conditions, specifically diseases like Alzheimer’s disease and its related dementia (ADRD), which have poor prognosis and lack prevention and treatment strategies. Although we do not fully understand the complex pathology of ADRD, emerging evidence indicates that abnormalities in th...

This study investigates the potential of resting-state electroencephalography (EEG) to differentiate between healthy individuals, those with mild cognitive impairment (MCI), and dementia. Early diagnosis of Alzheimer’s disease (AD) is critical, yet current methods are costly and invasive. EEG, as a non-invasive and portable tool, shows promise for...

Background: It has previously been shown that microbial metabolic pathways are differentially activated in immunotherapy resistance, hence can serve as potential biomarker as well as target for therapeutic intervention. With the advent of Immune Checkpoint Blockers (ICB) in the neoadjuvant (NA) setting of locally advanced (LA) TNBC, we hypothesized...

593 Background: It has previously been shown that microbial metabolic pathways are differentially activated in immunotherapy resistance, hence can serve as potential biomarker as well as target for therapeutic intervention. With the advent of Immune Checkpoint Blockers (ICB) in the neoadjuvant (NA) setting of locally advanced (LA) TNBC, we hypothes...

Despite the development of new and highly effective cancer therapies, emerging evidence suggests that these treatments are associated with long-term side effects, which may contribute to cognitive impairment (CI) or dementia in cancer survivors. Many of these side effects are linked to gut health and a perturbed gut microbiome. However, the role of...

The global population is aging, facing a substantial burden of age-related disorders, including cognitive impairment (CI), Alzheimer's disease (AD), and related dementias (ADRD). The lack of effective strategies for preventing and treating these conditions can be attributed to our incomplete understanding of the biology of aging. Emerging evidence...

Aging-related abnormalities in gut microbiota are associated with cognitive decline, depression, and anxiety, but underlying mechanisms remain unstudied. Here, our study demonstrated that transplanting old gut microbiota to young mice induced inflammation in the gut and brain coupled with cognitive decline, depression, and anxiety. We observed dimi...

Abnormalities in gut microbiome contribute to age-related diseases, causal to unhealthy aging, and early mortality, but mechanisms still remain largely unknown. Our recent research shows that old microbiota lacks the capacity to produce beneficial metabolites like short-chain fatty acids (SCFAs), which in turn promote gut permeability and systemic...

Advancements in oncology research have led to increased survivorship in patients with cancer. However, cancer treatments like chemotherapy cause debilitating side effects including multi-organ dysfunction and increased risk for chronic diseases, which mimic accelerated aging. Abnormalities in the gut microbiome composition (dysbiosis) increase infl...

Alzheimer’s disease (AD) is a detrimental public health problem affecting millions of older adults in the USA alone, with no or limited treatment options. Emerging evidence indicates the pivotal role of gut microbiota in AD pathology, but mechanisms remain largely unknown. Also, microbiome modulators like probiotics are proven beneficial in prevent...

The prevalence of age-related cognitive decline and dementia is increasing in older adults, with limited prevention and therapeutic options, increasing tremendous burden on healthcare system. Alzheimer’s disease (AD) is the most common age-related cognitive disorder, for which no treatment is available when its pathology is fully developed. Althoug...

Significant scientific advancements have resulted in new and effective therapies for patients with cancer. Although this leads to an increased cancer survivor population, there are several long-term side effects of cancer treatments, including a high risk of developing dementia. Emerging evidence shows that the gut microbiota significantly contribu...

Limited studies to-date have evaluated differences in gut microbiota across a global and temporal scale. Herein, we aim to examine the gut microbiota patterns across geography as defined by continent and countries and how gut microbiota vary across age groups within each geographic region. To approach these questions, we designed a large-scale anal...

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease characterized by cognitive and behavioral changes in older adults. Emerging evidence suggests poor oral health is associated with AD, but there is a lack of large-scale clinical studies demonstrating this link. Herein, we used the TriNetX database to generate clinical cohorts an...

Short-chain fatty acids (SCFAs) are key nutrients that play a diverse set of roles in physiological function, including regulating metabolic homeostasis. Generated through the fermentation of dietary fibers in the distal colon by the gut microbiome, SCFAs and their effects are partially mediated by their cognate receptors, including free fatty acid...

Alzheimer's disease (AD) is a progressive, age-related neurodegenerative disorder that affects a large proportion of the elderly population. It currently lacks effective treatments, placing a heavy burden on patients, families, healthcare systems, and society. This is mainly due to our limited comprehension of the pathophysiology of AD progression,...

Aging is associated with cellular and physiological changes, which significantly reduce the quality of life and increase the risk for disease. Geroprotectors improve lifespan and slow the progression of detrimental aging-related changes such as immune system senescence, mitochondrial dysfunction, and dysregulated nutrient sensing and metabolism. Em...

As we age, our organ functions gradually decline. Circulating factors in the blood and the integrity of organ barriers can become dysfunctional, resulting in a condition known as leaky syndrome. This condition involves the unregulated exchange or leakage of components between organs. However, the triggers of leaky syndrome, as well as its role in a...

The prevalence of age-related cognitive disorders/dementia is increasing, and effective prevention and treatment interventions are lacking due to an incomplete understanding of aging neuropathophysiology. Emerging evidence suggests that abnormalities in gut microbiome are linked with age-related cognitive decline and getting acceptance as one of th...

Sleep is a fundamental medicine for cardiac homeostasis, and sleep‐deprived individuals are prone to higher incidences of heart attack. The lipid‐dense diet (obesogenic diet‐OBD) is a cumulative risk factor for chronic inflammation in cardiovascular disease; thus, understanding how sleep fragmentation (SF) in an obesity setting impacts immune and c...

Objective Ample evidence exists for the role of abnormal gut microbiota composition and increased gut permeability (‘leaky gut’) in chronic inflammation that commonly co-occurs in the gut in both obesity and diabetes, yet the detailed mechanisms involved in this process have remained elusive. Design In this study, we substantiate the causal role o...

Disclosure summary Dr. Yadav is Chief Scientific Officer and Co-Founder of Postbiotics Inc and has no conflict of interest with this work. All other authors have no conflicts of interest to disclose. Background Metformin is the only approved first-line oral glucose lowering agent for youth with type 2 diabetes mellitus (Y-T2DM) but often causes ga...

The prevalence of cognitive decline and dementia is increasing in older adults, their prognosis is poor. Multiple emerging evidence shows that early intervention can delay and /or prevent their progression, however, early-detection markers are invasive, expensive, and not easy to routinely measure. Saliva can be an attractive source of early cognit...

The prevalence of age-related cognitive disorders is increasing. Effective prevention and treatment interventions are unavailable due to a poor understanding of aging biology. Multiple emerging evidence indicates that the gut microbiome is linked with age-related disorders; however, their clinical importance in differentiating and predicting the ri...

Chronic inflammation is a key risk factor for age‐related progression of cognitive decline and Alzheimer’s disease (AD); however, its etiology remains elusive. Multiple emerging evidence indicates that abnormalities in the gut microbiome (dysbiosis) contribute to the pathology of cognitive decline and Alzheimer’s disease, by elevating gut permeabil...

Correction for 'Bioactive peptides derived from milk proteins and their health beneficial potentials: an update' by Ravinder Nagpal et al., Food Funct., 2011, 2, 18-27, DOI: 10.1039/C0FO00016G.

6055 Background: Gut microbiome has emerged as an important predictor of response to ICB therapy in various cancers, most notably in melanoma. Due to functional redundancy of microbiota, there has been lack of consistency in gut microbial signature associated with ICB response. Microbial metabolites in addition to taxonomy may play a superior role...

[This corrects the article DOI: 10.1155/2012/902917.].

Human lifestyle and dietary behaviors contribute to disease onset and progression. Neu-rodegenerative diseases (NDDs), considered multifactorial disorders, have been associated with changes in the gut microbiome. NDDs display pathologies that alter brain functions with a tendency to worsen over time. NDDs are a worldwide health problem; in the US a...

Multiple emerging evidence indicates that the gut microbiota contributes to the pathology of Alzheimer’s disease (AD)—a debilitating public health problem in older adults. However, strategies to beneficially modulate gut microbiota and its sensing signaling pathways remain largely unknown. Here, we screened, validated, and established the agonists...

Increased chronic inflammation is one of the key risk factors of aging-related disorders although its precise etiology remains elusive. Here, we demonstrate that aged, but not young, microbiota triggers inflammation by promoting gut permeability (leaky gut) via disruption of mucus barriers. Levels of the beneficial short-chain fatty acid, butyrate,...

Gut microbiota and its metabolites like short chain fatty acids (SCFAs) are linked with pathology of Alzheimer’s disease (AD)- a debilitating public health problem in older adults. However, strategies to beneficially modulate gut microbiota and its sensing signaling pathways remain largely unknown. Here, we screened, validated and established the a...

Decade old studies demonstrated that microbes living in our gut (microbiota) contribute in both maintaining normal metabolic function and pathology of metabolic diseases such as obesity and diabetes. Emerging evidence suggest that gut microbiota influences the personalized effects of diets and drugs, and impact–gut brain axis and leaky gut-inflamma...

Inflammation is a major risk factor of morbidity and mortality in older adults. Although its precise etiology is unknown, low-grade inflammation in older adults is commonly associated with increased intestinal epithelial permeability (leaky gut) and abnormal (dysbiotic) gut microbiota. The increasing older population and lack of treatments to reduc...

Inflammation is a major risk factor of morbidity and mortality in older adults. Although its precise etiology is unknown, low grade inflammation in older adults is commonly associated with increased intestinal epithelial permeability (leaky gut) and abnormal (dysbiotic) gut microbiota. The lack of treatments to reduce aging‐related microbiota dysbi...

Aging-related illnesses are increasing and effective strategies to prevent and/or treat them are lacking. This is because of a poor understanding of therapeutic targets. Low-grade inflammation is often higher in older adults and remains a key risk factor of aging-related morbidities and mortalities. Emerging evidence indicates that abnormal (dysbio...

Increased inflammation associated with leaky gut is a major risk factor for morbidity and mortality in older adults; however, successful preventive and therapeutic strategies against these conditions are not available. In this study, we demonstrate that a human-origin Lactobacillus paracasei D3-5 strain (D3-5), even in the non-viable form, extends...

Increased inflammation associated with leaky gut is a major risk factor for morbidity and mortality in older adults; however, successful preventive and therapeutic strategies are not available to ameliorate these conditions. In this study, we demonstrate that a human-origin Lactobacillus paracasei D3-5 strain (D3-5), even when dead, extended life s...

β-Arrestins are major regulators of G protein-coupled receptor-mediated signaling processes. Their potential roles in regulating adipocyte function in vivo remain unexplored. Here we report the novel finding that mice lacking β-arrestin-2 (barr2) selectively in adipocytes show significantly reduced adiposity and striking metabolic improvements when...

This study aimed to determine the association between non-high-fat diet-induced obesity- (non-DIO-) associated gut microbiome dysbiosis with gut abnormalities like cellular turnover of intestinal cells, tight junctions, and mucin formation that can impact gut permeability. We used leptin-deficient (Lep ob/ob ) mice in comparison to C57BL/6J control...

Supplementary Figure S1: body weight (a), fasting (b), and fed (c) blood glucose levels of Lepob/ob and C57BL/6J mice (n = 8 in each group). Glucose tolerance test (d) and insulin tolerance test (e), as well as area under the curve during GTT (f) and ITT (g), of Lepob/ob and B6 mice. Values presented here are average ± SEM/SD. p values are defined...

Intraperitoneal administration of the melanocortin agonist melanotan II (MTII) to mice causes a profound, transient hypometabolism/hypothermia. It is preserved in mice lacking any one of melanocortin receptors 1, 3, 4, or 5, suggesting a mechanism independent of the canonical melanocortin receptors. Here we show that MTII-induced hypothermia was ab...

Extracellular adenosine is a danger/injury signal that initiates protective physiology, such as hypothermia. Adenosine has been shown to trigger hypothermia via agonism at A1 and A3 adenosine receptors (A1AR, A3AR). Here, we find that adenosine continues to elicit hypothermia in mice null for A1AR and A3AR and investigated the effect of agonism at...

Various commensal enteric and pathogenic bacteria may be involved in the pathogenesis of inflammatory bowel diseases (IBDs), a chronic condition with a pathogenic background that involves both immunogenetic and environmental factors. IBDs comprising of Crohn's disease, and ulcerative colitis, and pauchitis are chronic inflammatory conditions, and k...

Small mammals have the ability to enter torpor, a hypothermic, hypometabolic state, allowing impressive energy conservation. Administration of adenosine or adenosine 5'-monophosphate (AMP) can trigger a hypothermic, torpor-like state. We investigated the mechanisms for hypothermia using telemetric monitoring of body temperature in wild type and rec...

Prevalence of type 2 diabetes and its life threatening complications i.e. cardiovascular diseases (CVDs) and hypertension, is increasing rapidly around the globe. India has largest diabetic population of diabetics in the world, and rapid growth is expected in coming years. Plethora of literature suggest that dietary, factors, physical activity, gen...

Daily diet affects whole body metabolism, and the types of diet we eat contributes to development of our body weight and prevention or progression of metabolic diseases i.e. obesity, diabetes and cardiovascular diseases. Several epidemiological and large scale studies have shown that diet enriched with whole grain improves metabolic function and pr...

Aim: To investigate the presence of total gut viral content in obese mice, and establish correlation with obesity associated metabolic measures and gut microbiome. Methods: Fresh fecal samples were collected from normal and obese (Leptin deficient: Lep(ob/ob)) mice. Total viral DNA and RNA was isolated and quantified for establishing the correla...

Nature Communications 7: Article number: 10268 10.1038/ncomms10268 (2016); Published: January082016; Updated: March032016 The financial support for this article was not fully acknowledged. The Acknowledgements should have included the following: This work was supported by the intramural research program of the NIMH (ZIA-MH-002498-24).

Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including G s -linked GPCRs. At present, the pote...

Supplementary Figures 1-9 and Supplementary Tables 1-3

The aim of this study was to assess whether the concomitant supplementation of certified fermented papaya preparation (FPP, ORI, Gifu, Japan) together with iron supplementation could beneficially affect lipid peroxidation either systemically and at a intraluminal gut level in women with low iron stores. Treatment compliance and iron absorption was...

The term probiotic is derived from Greek and means ‘for life’ as opposed to antibiotics which means ‘against life’. The history of probiotics began with the consumption of fermented foods. Consumption of fermented foods was first observed in ancient Greeks and Romans (Gismondo et al. 1999, Guarner et al. 2005). In 1907, Ellie Metchnikoff, a Nobel P...

Increased hepatic glucose production is a key pathophysiological feature of type 2 diabetes. Like all other cell types, hepatocytes express many G protein-coupled receptors (GPCRs) that are linked to different functional classes of heterotrimeric G proteins. The important physiological functions mediated by Gs-coupled hepatic glucagon receptors are...

The release of insulin from pancreatic β-cells is regulated by a considerable number of G protein-coupled receptors (GPCRs). During the past several years, we have focused on the physiological importance of β-cell M3 muscarinic acetylcholine receptors (M3Rs). At the molecular level, the M3R selectively activates G proteins of the Gq family. Phenoty...

Muscarinic receptor-based designer receptors have emerged as powerful novel tools to study G-protein-coupled receptor (GPCR) signaling and physiology. These new designer GPCRs, which are most frequently referred to as DREADDs (designer receptors exclusively activated by designer drug), are unable to bind acetylcholine, the endogenous muscarinic rec...

The aim of the present study was to test the possible effects of a novel sturgeon-derived compound (LD-1227) on inflammatory markers related to metabolic nuclear receptors in patients with metabolic syndrome. The study population consisted of 76 patients with metabolic syndrome and 30 healthy subjects who were maintained to their current treatments...

Type 2 diabetes (T2D) has emerged as a major threat to human health in most parts of the world. Therapeutic strategies aimed at improving pancreatic β cell function are predicted to prove beneficial for the treatment of T2D. In the present study, we demonstrate that drug-mediated, chronic, and selective activation of β cell Gq signaling greatly imp...

For decades, the hallmark of medical treatment for cancer has been intravenous cytotoxic chemotherapy, where these drugs target rapidly dividing cells, including cancer cells and certain normal tissues. As a result, many patients experience the classic toxicities of alopecia, gastrointestinal symptoms, and myelosuppression. In the past decade, howe...

The incidence of obesity and diabetes has been increased with alarming rate in recent years and became a common problem around the globe including developing as well as in developed countries with incalculable social costs. Obesity and type 2 diabetes are two common co-morbidities occur together. Obesity and diabetes is closely associated with many...

Increasing prevalence of type 2 diabetes and obesity is raising the risk of cardiovascular diseases and cancer. This is because of lack of effective preventive/therapeutic strategies to combat these health ailments. Recently, gut flora has been considered as an important player in regulation of energy homeostasis and has been proposed as a potentia...

Diabetes is a chronic metabolic syndrome due to insulin deficiency and is associated with increased oxidative stress in vivo. Oxidative stress including, increased production of reactive oxygen species (ROS) in vivo, can lead to cellular biomolecule damage. Such damage has been suggested to contribute to the pathogenesis of diabetes mellitus. Genot...

The genotoxic and mutagenic effects of two commonly used organochlorine pesticides, lindane (LND) and endosulfan (ENS), and two commonly used organophosphate pesticides, chlorpyrifos (CPF) and monocrotophos (MCP) was assessed using in vivo mouse bone marrow micronucleus test and in vitro Ames Salmonella/ microsome mutagenicity test. The results sho...

The increasing epidemic of diabetes mellitus around the globe is increasing the risk of various other chronic diseases i.e. coronary artery diseases, myocardial infarction, hypertension, dyslipidemia and number of other complicated disorders. Diabetes mellitus is clinically characterized by a marked increase in blood glucose levels and is associate...

Dietary lipids may affect sperm membrane structure, fluidity and its susceptibility to oxidative phenomena which may lead to altered sperm viability and proper binding to eggs. Given the recently demonstrated beneficial effects of fish oil diets on turkey fertility and embryo viability, the aim of this study was to test a caviar-derived marine prod...

The role of oxidants in viral diseases is fairly complex because it includes metabolic regulation both of host metabolism and viral replication. However, a role for reactive oxygen species (ROS) and reactive nitrogen species (RNS) as mediators of virus-induced lung damage is supported by studies and antioxidants can thus be expected to act at many...

The aim of this study is to test the activity of a marine bioactive compound containing high-purity caviar-derived DNA, collagen elastin and protein extracts from sturgeon (LD-1227, Caviarlieri, Laboratoires Dom, Switzerland) to exert neuroprotective properties in an experimental setting while also being potential triggers of neurogenesis in a sepa...

In the industrialized world, functional foods have become a part of an everyday diet and are demonstrated to offer potential health benefits beyond the widely accepted nutritional effects. Currently, the most important and frequently used functional food compounds are probiotics and prebiotics, or they are collectively known as 'synbiotics'. Moreov...

Cardiovascular diseases are one of the major causes of deaths in adults in the western world. Elevated levels of certain blood lipids have been reported to be the principal cause of cardiovascular disease and other disabilities in developed countries. Several animal and clinical trials have shown a positive association between cholesterol levels an...

The cow and its milk have been held sacred in the world since the dawn of human civilization. Indian ancient Vedic texts describe the virtues of milk and dairy products, as is authenticated by modern scientific principles and proofs. Therefore, milk has been considered as one of the most natural and highly nutritive part of a daily balanced diet. C...

The aim of this study was to evaluate the effect of DTS-phytocompound on oxidant-antioxidant balance and protein damage in the kidneys of rats administered high doses of fructose. Adult male Wistar rats were divided into four groups. Group A received a control diet, whereas groups B and C were fed a high-fructose diet (60 g/100 g), the latter with...

We tested the activity of the marine nutraceutical CL-1222 added with a coenzyme Q10 (CoQ10)-lutein-selenium component (Celergen(®), Laboratoires-Dom, Switzerland) to protect human fibroblasts against ultraviolet A (UVA)-induced photoaging. Cells obtained from 22- to 39-year-old healthy donors were pretreated with CL-1222 before UV irradiation, as...

This study tested the activity of LD-1227, which contains a caviar-derived homogenate added with coenzyme Q(10) (CoQ(10))-selenium component (CaviarLieri(®), Lab-Dom, Switzerland), in aged human skin and its potential role on skin mitochondria function. Human dermal fibroblasts were obtained from healthy donors over 70 years old and treated with LD...

We tested a biofermented nutraceutical (FPP) that has been previously shown to positively modulate nitric oxide (NO). Forty-two healthy middle-aged subjects were given 3 grams of FPP three times a day for 6 weeks, and tests were repeated at 3 and 6 weeks; the control group was given a placebo. Flow-mediated dilation (FMD) was measured together with...

"Functional foods" represent an emerging opportunity and they will certainly play a consistent and important role in future too. Such a new perspective entirely depends on the growing attention paid by nutritionists to the development of new innovating solutions aiming at acting on organic systems as well as on more general topics relating to consu...