Microbial Neuro-Immune Interactions and the Pathophysiology of IBD

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a group of debilitating disorders affecting patient’s quality of life and with unknown aetiology. The collected evidence indicates that individuals can develop IBD as a result of genetic susceptibility, a dysregulated immune response and the influence of certain environmental factors. Common symptomatology includes abdominal pain, fever and bowel diarrhoea with blood and/or mucus excretion. The location and extent of disease differ between UC and CD, affecting the mucosal layer in the colon in UC patients, whereas in CD patients, a transmural inflammation is found anywhere in the gastrointestinal tract. Factors associated with IBD pathophysiology include alterations in immune responses, characterized by an atypically T helper (Th)-2 profile in UC, and a Th1/Th17 profile in CD, modifications in epithelial barrier function and alterations in the commensal microbiota composition with blooming of specific pathobionts, for example, adherent-invasive Escherichia coli (AIEC), and with diet. Recent research has uncovered that inflammation, per se, can activate the enteric nervous system inducing neurogenic inflammation and increasing visceral sensitivity, leading to pain. Similarly, alterations in the commensal microbiota composition/ligands have also led to modifications in intestinal nociceptive markers and in visceral pain. In this chapter, we aim to review the mechanisms implicated in microbial neuro-immune axis and its potential contribution to IBD pathophysiology and symptomatology. We focus on the findings identified in animal models and in IBD patients and on the prospective translation of targeting the microbial neuro-immune axis as future therapeutic treatment for intestinal inflammatory conditions

Crop fertility conditions in North-Eastern Gaul during the La Tène and Roman periods: a combined stable isotope analysis of archaeobotanical and archaeozoological remains.

Considerable archaeobotanical datasets describe cereal cultivation in north-eastern France, from the Iron Age to the Roman period. This study aims to complement these by using stable isotope analysis on charred cereal grains. Soil fertility was investigated through d15N and d13C analyses of 1480 charred cereal grains, dated from the Late La Tène to the Late Antiquity periods. In the Île-de-France, charred grain D13C values suggested good hydric conditions, with drier episodes in the 1st and 3rd century AD; while in Champagne, the lower D13C values for spelt reflect the lower water holding capacity of the chalky soils. A wide range of cereal d15N values (0.8 - 8.7 ¿) implies a wide range of soil fertility conditions. Jouars-Pontchartrain and Palaiseau (Île-de-France) yielded the highest cereal d15N values, whereas Acy-Romance (Champagne) delivered among the lowest. From these three sites, the d15N values of red deer bone collagen were used to estimate the reference d15N values for unmanured plants. Unlike in Acy-Romance, there were significant differences in Palaiseau and Jouars-Pontchartrain, indicating that the cultivated cereals inherited their high d15N values from manured soil. At Jouars-Pontchartrain, the d15N value (almost 9¿) suggested a high trophic level manuring source, possibly from pig and/or human faeces

The impact of western diet and nutrients on the microbiota and immune response at mucosal interfaces

Recent findings point toward diet having a major impact on human health. Diets can either affect the gut microbiota resulting in alterations in the host's physiological responses or by directly targeting the host response. The microbial community in the mammalian gut is a complex and dynamic system crucial for the development and maturation of both systemic and mucosal immune responses. Therefore, the complex interaction between available nutrients, the microbiota, and the immune system are central regulators in maintaining homeostasis and fighting against invading pathogens at mucosal sites. Westernized diet, defined as high dietary intake of saturated fats and sucrose and low intake of fiber, represent a growing health risk contributing to the increased occurrence of metabolic diseases, e.g., diabetes and obesity in countries adapting a westernized lifestyle. Inflammatory bowel diseases (IBD) and asthma are chronic mucosal inflammatory conditions of unknown etiology with increasing prevalence worldwide. These conditions have a multifactorial etiology including genetic factors, environmental factors, and dysregulated immune responses. Their increased prevalence cannot solely be attributed to genetic considerations implying that other factors such as diet can be a major contributor. Recent reports indicate that the gut microbiota and modifications thereof, due to a consumption of a diet high in saturated fats and low in fibers, can trigger factors regulating the development and/or progression of both conditions. While asthma is a disease of the airways, increasing evidence indicates a link between the gut and airways in disease development. Herein, we provide a comprehensive review on the impact of westernized diet and associated nutrients on immune cell responses and the microbiota and how these can influence the pathology of IBD and asthma

Suppression of glycogen synthesis as a treatment for Lafora disease: Establishing the window of opportunity

Lafora disease (LD) is a fatal adolescence-onset neurodegenerative condition. The hallmark of LD is the accumulation of aberrant glycogen aggregates called Lafora bodies (LBs) in the brain and other tissues. Impeding glycogen synthesis from early embryonic stages by genetic suppression of glycogen synthase (MGS) in an animal model of LD prevents LB formation and ultimately the pathological manifestations of LD thereby indicating that LBs are responsible for the pathophysiology of the disease. However, it is not clear whether eliminating glycogen synthesis in an adult animal after LBs have already formed would halt or reverse the progression of LD. Herein we generated a mouse model of LD with inducible MGS suppression. We evaluated the effect of MGS suppression at different time points on LB accumulation as well as on the appearance of neuroinflammation, a pathologic trait of LD models. In the skeletal muscle, MGS suppression in adult LD mice blocked the formation of new LBs and reduced the number of glycogen aggregates. In the brain, early but not late MGS suppression halted the accumulation of LBs. However, the neuroinflammatory response was still present, as shown by the levels of reactive astrocytes, microglia and inflammatory cytokines. Our results confirm that MGS as a promising therapeutic target for LD and highlight the importance of an early diagnosis for effective treatment of the disease

Agronomic conditions and crop evolution in ancient Near East agriculture

The appearance of agriculture in the Fertile Crescent propelled the development of Western civilization. Here we investigate the evolution of agronomic conditions in this region by reconstructing cereal kernel weight and using stable carbon and nitrogen isotope signatures of kernels and charcoal from a set of 11 Upper Mesopotamia archaeological sites, with chronologies spanning from the onset of agriculture to the turn of the era. We show that water availability for crops, inferred from carbon isotope discrimination (Δ13C), was two- to fourfold higher in the past than at present, with a maximum between 10,000 and 8,000 cal BP. Nitrogen isotope composition (δ15N) decreased over time, which suggests cultivation occurring under gradually less-fertile soil conditions. Domesticated cereals showed a progressive increase in kernel weight over several millennia following domestication. Our results provide a first comprehensive view of agricultural evolution in the Near East inferred directly from archaeobotanical remains