The incidence of inflammatory bowel disease is increasing all over the world, especially in industrialized countries. The aim of the present work was to verify the anti-inflammatory activity of metabolites. In particular, cell-free supernatants of Lactobacillus acidophilus, Lactobacillus casei, Lactococcus lactis, Lactobacillus reuteri, and Saccharomyces boulardii have been investigated. Metabolites produced by these probiotics were able to downregulate the expression of PGE-2 and IL-8 in human colon epithelial HT-29 cells. Moreover, probiotic supernatants can differently modulate IL-1β, IL-6, TNF-α, and IL-10 production by human macrophages, suggesting a peculiar anti-inflammatory activity. Furthermore, supernatants showed a significant dose-dependent radical scavenging activity. This study suggests one of the mechanisms by which probiotics exert their anti-inflammatory activity affecting directly the intestinal epithelial cells and the underlying macrophages. This study provides a further evidence to support the possible use of probiotic metabolites in preventing and downregulating intestinal inflammation as adjuvant in anti-inflammatory therapy.

The gut microbiota is increasingly recognized as an important regulator of host immunity and brain health. The aging process yields dramatic alterations in the microbiota, which is linked to poorer health and frailty in elderly populations. However, there is limited evidence for a mechanistic role of the gut microbiota in brain health and neuroimmunity during aging processes. Therefore, we conducted fecal microbiota transplantation from either young (3-4 months) or old (19-20 months) donor mice into aged recipient mice (19-20 months). Transplant of a microbiota from young donors reversed agingassociated differences in peripheral and brain immunity, as well as the hippocampal metabolome and transcriptome of aging recipient mice. Finally, the young donor-derived microbiota attenuated selective age-associated impairments in cognitive behavior when transplanted into an aged host. Our results reveal that the microbiome may be a suitable therapeutic target to promote healthy aging.Aging triggers metabolic and immune alterations that lead to perturbation of brain function and behavior, including impairments in hippocampal-associated cognitive behavior 1 . Notably, the gut microbiota, encompassing the population of trillions of microorganisms, undergoes a parallel community shift, which has been correlated to changes in host frailty and cognition 2,3 .Animal models have shown specific roles for the microbiota in shaping hallmarks of aging in the gut 4,5 . Moreover, the consequences of an elderly-associated microbiota on a young host involve alterations in host immunity, neurogenesis and cognition [6][7][8][9] . Notably, transferring microbiota from young fish (African turquoise killifish) into middle-aged fish improves lifespan and motor behavior 10 . However, it is completely unknown whether microbiota from young donors can restore aging-associated impairments in mammals.To determine whether fecal microbiota transplantation (FMT) from young mice can ameliorate aging-induced neurocognitive and immune impairments, we collected fecal microbiota from naive young mice (3-4 months) and transplanted this into aged mice ('aged yFMT' , 19-20 months). A separate group of aged mice received fecal microbiota from naive old mice to control for handling during FMT administration ('aged oFMT' ,(19)(20). To allow aging-associated comparisons, naive young mice received the same yFMT mixture ('young yFMT'). We found aging-associated differences in microbiota (Fig. 1 and Supplementary Tables 1 and 2), immunity (Fig. 2 and Extended Data Figs. 2 and 3), hippocampal neurogenesis (Extended Data Fig. 2), hippocampal metabolomics (Fig. 3, Extended Data Fig. 7 and Supplementary Table 3) and transcriptomics (Fig. 2 and Extended Data Fig. 7), and behavior (Fig. 4 and Extended Data Fig. 5); some, but not all, of which were attenuated by microbiota transplantation from a young mouse into an aged host. Our research offers the possibility that a microbiota from a young individual may have beneficial effects when given to an aged host.

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Many studies highlighted that a bidirectional communication between the gut and the central nervous system (CNS) exists. A vigorous immune response to antigens must be avoided, and pathogenic organisms crossing the gut barrier must be detected and killed. For this reason, the immune system developed fine mechanisms able to maintain this delicate balance. The microbiota is beneficial to its host, providing protection against pathogenic bacteria. It is intimately involved in numerous aspects of host physiology, from nutritional status to behavior and stress response. In the last few years, the implication of the gut microbiota and its bioactive microbiota-derived molecules in the progression of multiple diseases, as well as in the development of neurodegenerative disorders, gained increasing attention. The purpose of this review is to provide an overview of the gut microbiota with particular attention toward neurological disorders and mast cells. Relevant roles are played by the mast cells in neuroimmune communication, such as sensors and effectors of cytokines and neurotransmitters. In this context, the intake of beneficial bacterial strains as probiotics could represent a valuable therapeutic approach to adopt in combination with classical therapies. Further studies need to be performed to understand if the gut bacteria are responsible for neurological disorders or if neurological disorders influence the bacterial profile.

Autism spectrum disorders (ASD) is one of the most severe developmental disorders, affecting on average 1 in 150 children worldwide. There are limited treatment options for ASD symptoms and there is therefore a great need for more effective strategies to improve quality of life in ASD subjects. The gut microbiome has recently emerged as a therapeutic target in ASD. A novel modulator of the gut microbiome, the traditionally fermented milk drink kefir, has recently been shown to modulate the microbiota and decrease repetitive behaviour, one of the hallmarks of ASD. As such, we hypothesised that kefir could ameliorate the behavioural phenotype of ASD in the animal model of ASD; the BTBR T + Itpr3 tf /J mouse strain. Adult mice were administered either kefir (UK4) or milk control for 3 weeks as treatment lead-in, after which they were assessed for their behavioural phenotype using a battery of tests. In addition, we assessed systemic immunity by flow cytometry. We found that kefir decreased repetitive behaviour. Furthermore, kefir prolonged stress-induced increases in corticosterone 60 minutes post-stress, which was accompanied by an ameliorated innate immune response as measured by LY6C hi monocyte levels. Furthermore, kefir increased the levels of antiinflammatory Treg cells in mesenteric lymph nodes. Altogether, our data show that kefir modulates peripheral immunity in an anti-inflammatory manner and can ameliorate specific ASD behavioural dysfunctions, indicating that kefir supplementation might prove a viable strategy in improving quality of life in ASD subjects. Background Autism spectrum disorder (ASD) is one of the most severe neurodevelopmental conditions, affecting on average 1 in 150 children worldwide (Lyall et al. 2017). ASD is hallmarked by impaired social communication skills and enhanced engagement in repetitive behaviours, frequently co-occurring with intellectual disability (Association 2013). In addition, there is a growing body of evidence showing that ASD is associated with substantial differences in gut microbiota composition, as well as symptoms of gastrointestinal dysfunction, such as altered bowel habits, bloating, abdominal pain and increased intestinal permeability (D'

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Prevalence of thyroid dysfunction and its impact on cognition in older people has been demonstrated, but many points remain unclarified. In order to study the effect of aging on the thyroid gland, we compared the thyroid gland of very old mice with that of younger ones. We have first investigated the changes of thyroid microstructure and the possibility that molecules involved in thyroid function might be associated with structural changes. Results from this study indicate changes in the height of the thyrocytes and in the amplitude of interfollicular spaces, anomalous expression/localization of thyrotropin, thyrotropin receptor, and thyroglobulin aging. Thyrotropin and thyrotropin receptor are upregulated and are distributed inside the colloid while thyroglobulin fills the interfollicular spaces. In an approach aimed at defining the behavior of molecules that change in different physiopathological conditions of thyroid, such as galectin-3 and sphingomyelinase, we then wondered what was their behavior in the thyroid gland in aging. Importantly, in comparison with the thyroid of young animals, we have found a higher expression of galectin-3 and a delocalization of neutral sphingomyelinase in the thyroid of old animals. A possible relationship between galectin-3, neutral sphingomyelinase, and aging has been discussed.