Sanjoy Ghosh

Systemic inflammatory diseases can be influenced by dietary intake, with gastrointestinal dysfunction driving both metabolic and behavioural changes mirroring the altered inflammatory profile. Additionally, the use of live biotherapeutic products (LBPs) shows promise for treating metabolic and inflammatory diseases, but their efficacy is limited by poor persistence in inflamed gut environments. Designed to utilize inflammatory byproducts, the LBP EcN:: ttr has proven efficacy in the treatment of acute and chronic colitis, however its effects on the metabolic and behavioural patterns remain uncharacterized. We evaluated the effects of EcN:: ttr on mice fed a proinflammatory omega-6 PUFA-rich diet. EcN:: ttr -treated mice exhibited notable changes in the gut, including an improved expression of tight junction protein occludin, accompanied by reduced serum lipopolysaccharide (LPS) - binding protein, indicating protection against endotoxemia. EcN:: ttr improved insulin sensitivity compared to the parental strain, associated with increased hepatic insulin receptor expression and reduced GSK3β activation and endoplasmic reticulum stress. Secondary bile acids in mice treated with EcN:: ttr were more abundant, with increases in those associated with resolving diarrhea and bile acid detoxification. Behavioural assessment highlighted a normalization of long-term memory along with a reduction of stress management behaviours. Altogether, EcN:: ttr restores gut–liver–brain axis function through coordinated modulation of inflammation, barrier integrity, and bile acid metabolism. Highlights: Live Biotherapeutic Product EcN:: ttr , designed with a fitness advantage to survive inflammation, and provides protection against a proinflammatory omega 6-rich diet Administration of EcN:: ttr improved metabolic outcomes including increasing insulin sensitivity EcN:: ttr increased the abundance of secondary bile acids including those that modulate bile acid detoxification Behavioural parameters were normalized in mice given EcN:: ttr EcN:: ttr partially normalizes gut-liver-brain axis through restoring barrier integrity, modulating inflammation and improving secondary bile acid metabolism

Glyphosate, a widely used herbicide in North America, has become prevalent in the food supply, raising concerns about potential health impacts. In this exploratory study, male and female F0 mice were exposed to glyphosate through drinking water during mating and gestation. We investigated whether prenatal exposure at dietary-relevant levels (0.01 mg/kg/day, Average American Diet, [AAD]) or the U.S. EPA’s acceptable daily intake (1.75 mg/kg/day, [EPA upper limit]) altered gut, metabolic, and behavioral outcomes across two generations in mice with or without genetic susceptibility to colitis ( Muc2 ^+/- and Muc2 ^-/- , respectively). Healthy ( Muc2 ^+/- ) offspring of glyphosate-exposed mice exhibited colonic goblet cell depletion, reduced mucin-2 expression, and pro-inflammatory cytokine profiles in both F1 and F2 generations. These healthy ( Muc2 ^+/- ) offspring also developed metabolic dysfunction, including impaired glucose tolerance, insulin resistance, and reduced GLP-1 in serum. Behavioral deficits were also observed in healthy ( Muc ^+/- ) mice including reduced locomotion and working memory, and these changes were associated with altered microbiome composition and gut-brain mediators. These findings suggest that prenatal glyphosate exposure, even below regulatory thresholds, may disrupt multiple physiological systems across generations, highlighting the need for further research and regulatory consideration.

There is a growing appreciation that the interaction between diet, the gut microbiota and the immune system contribute to the development and progression of inflammatory bowel disease (IBD). A mounting body of scientific evidence suggests that high-fat diets exacerbate IBD; however, there is a lack of information on how specific types of fat impact colitis. The Mediterranean diet (MD) is considered a health-promoting diet containing approximately 40% total fat. It is not known if the blend of fats found in the MD contributes to its beneficial protective effects. Mice deficient in the mucin 2 gene (Muc 2^−/−) were weaned to 40% fat, isocaloric, isonitrogenous diets. We compared the MD fat blend (high monounsaturated, 2:1 n-6:n-3 polyunsaturated and moderate saturated fat) to diets composed of corn oil (CO, n-6 polyunsaturated-rich), olive oil (monounsaturated-rich) or milk fat (MF, saturated-rich) on spontaneous colitis development in Muc2^−/− mice. The MD resulted in lower clinical and histopathological scores and induced tolerogenic CD103+ CD11b+ dendritic, Th22 and IL-17+ IL-22+ cells necessary for intestinal barrier repair. The MD was associated with beneficial microbes and associated with higher cecal acetic acid levels negatively correlated with colitogenic microbes like Akkermansia muciniphila. In contrast, CO showed a higher prevalence of mucin-degraders including A. muciniphila and Enterobacteriaceae, which have been associated with colitis. A dietary blend of fats mimicking the MD, reduces disease activity, inflammation-related biomarkers and improves metabolic parameters in the Muc2^−/− mouse model. Our findings suggest that the MD fat blend could be incorporated into a maintenance diet for colitis. Graphical abstract

The role of the microbiome in health and disease has gained considerable attention and shed light on the etiology of complex diseases like inflammatory bowel disease (IBD) and metabolic syndrome (MetS). Since the microorganisms inhabiting the gut can confer either protective or harmful signals, understanding the functional network between the gut microbes and the host provides a comprehensive picture of health and disease status. In IBD, disruption of the gut barrier enhances microbe infiltration into the submucosae, which enhances the probability that gut-derived metabolites are translocated from the gut to the liver and pancreas. Considering inflammation and the gut microbiome can trigger intestinal barrier dysfunction, risk factors of metabolic diseases such as insulin resistance may have common roots with IBD. In this review, we focus on the overlap between IBD and MetS, and we explore the role of common metabolites in each disease in an attempt to connect a common origin, the gut microbiome and derived metabolites that affect the gut, liver and pancreas.

Omega-3 PUFA vs. NSAIDs for Preventing Cardiac Inflammation

Chronic inflammatory diseases like diabetes are on a rise in the Western world. Based on the tsunami of new cases every year, new therapeutic measures must be considered. A promising avenue might involve the attenuation of underlying inflammation through natural health products (NHPs). This is because most NHPs have a rich history in traditional medicine and might be considered safer under appropriate doses and conditions. However, the biggest impediment in NHP research is that rarely do these products come with verified health benefits or dosing schedules established through modern scientific research. Fulvic acid (FvA), one such NHP, comes from humic substances produced by microorganisms in soil. Traditional medicine and modern research claim FvA can modulate the immune system, influence the oxidative state of cells, and improve gastrointestinal function; all of which are hallmarks of diabetes. This minireview outlines the available peer-reviewed research on FvA and examines its anecdotal health claims. We show that although available research has been minimal, there is substantial evidence to pursue FvA research in preventing chronic inflammatory diseases, including diabetes.

In recent years, dietary polyunsaturated fatty acids (PUFA) have increased in parallel to sedentary behavior and diabetes across the world. To test any putative association between dietary PUFA and sedentary behavior or diabetes in females, we obtained country-specific, cross-sectional data on sedentary activity and diabetes prevalence from European Cardiovascular Statistics 2012. Age and gender-specific, nutritional data from each country were obtained from nutritional surveys as well. Socioeconomic (GDP), physical environment (urbanization index) and climatic confounders were accounted for each country. Upon analysis, we found a strong, positive association between sedentary lifestyle in 11-yr old girls (> = 2 hours of TV/ weekday) and dietary PUFA across 21 European countries. Further, a weak association of dietary PUFA and a strong relationship of per-capita GDP was established with elevated fasting blood glucose [(> = 7.0 mmol/L; or on medication] among 25+ year old adult females across 23 countries in Europe. In summary, we present novel ecological evidence that dietary PUFA is strongly associated with sedentary behavior among pre-teen girls and weakly associated with diabetes among adult women across Europe. In the latter group, per-capita GDP was a significant predictor for diabetes as well. Therefore, we recommend that prospective randomized controlled trials (RCTs) be implemented to evaluate if ubiquitous presence of dietary PUFA and low socioeconomic status are possible confounders when intervening to treat/prevent sedentary lifestyle or diabetes in female subjects in Western nations.

Anecdotal evidence suggests that the incorporation of n-6 polyunsaturated fatty acid (n-6 PUFA) containing oilseeds in dairy feeds depletes saturated fatty acids (SFA) in dairy fats such as butter. However, due to the lack of chemical evidence, the current status of n-6 PUFA or SFA in butter is unknown. We hypothesized that n-6 PUFA levels in commercial butter were inversely proportional to its SFA content and directly proportional to the extent of n-6 PUFA-rich oilseed production of its country of origin. We analyzed grass-fed and commercial butters from Australia, Belarus, Canada, China, England, France, Germany, Iceland, India, Israel, Japan, the Netherlands, New Zealand, Russia, and the United States via gas chromatography. Extent of n-6 PUFA containing oilseed production for countries was obtained from the FAOStat 2015 database. Globally, SFA from commercial butters had a strong negative correlation (Spearman r = −0.53, p = 0.025) with its n-6 PUFA content, with U.S. and Canadian butter demonstrating the highest n-6 PUFA as well as n-6/n-3 PUFA ratios. As predicted, we show that countries with >5% of its agricultural land dedicated to n-6 PUFA oilseed production demonstrate a “spillover” increase of n-6 PUFA in their commercial butters (Spearman r = 0.85, p = 0.0054). The overall significance of this study is that it presents novel evidence of the global impact of rising n-6 PUFA production on commercial butter fat composition. We hope these data will lead to inclusion of actual biochemical analyses of dairy fats in future clinical trials. We believe that this inclusion of analyses will better explain the differential health outcomes among different countries for such interventions.