Shared and unique transcriptomic signatures of antidepressant and probiotics action in the mammalian brain.

Understanding the shared and divergent mechanisms across antidepressant (AD) classes and probiotics is critical for improving treatment for mood disorders. Here we examine the transcriptomic effects of bupropion (NDRI), desipramine (SNRI), fluoxetine (SSRI) and a probiotic formulation (Lacidofil®) on 10 regions across the mammalian brain. These treatments massively alter gene expression (on average, 2211 differentially expressed genes (DEGs) per region-treatment combination), highlighting the biological complexity of AD and probiotic action. Intersection of DEG sets against neuropsychiatric GWAS loci, sex-specific transcriptomic portraits of major depressive disorder (MDD), and mouse models of stress and depression reveals significant similarities and differences across treatments. Interestingly, molecular responses in the infralimbic cortex, basolateral amygdala and locus coeruleus are region-specific and highly similar across treatments, whilst responses in the Raphe, medial preoptic area, cingulate cortex, prelimbic cortex and ventral dentate gyrus are predominantly treatment-specific. Mechanistically, ADs concordantly downregulate immune pathways in the amygdala and ventral dentate gyrus. In contrast, protein synthesis, metabolism and synaptic signaling pathways are axes of variability among treatments. We use spatial transcriptomics to further delineate layer-specific molecular pathways and DEGs within the prefrontal cortex. Our study reveals complex AD and probiotics action on the mammalian brain and identifies treatment-specific cellular processes and gene targets associated with mood disorders.

Psychobiotics and the Microbiota-Gut-Brain Axis: Where Do We Go from Here?

The bidirectional relationship between the gut microbiota and the nervous system is known as the microbiota-gut-brain axis (MGBA). The MGBA controls the complex interactions between the brain, the enteric nervous system, the gut-associated immune system, and the enteric neuroendocrine systems, regulating key physiological functions such as the immune response, sleep, emotions and mood, food intake, and intestinal functions. Psychobiotics are considered tools with the potential to modulate the MGBA through preventive, adjunctive, or curative approaches, but their specific mechanisms of action on many aspects of health are yet to be characterized. This narrative review and perspectives article highlights the key paradigms needing attention as the scope of potential probiotics applications in human health increases, with a growing body of evidence supporting their systemic beneficial effects. However, there are many limitations to overcome before establishing the extent to which we can incorporate probiotics in the management of neuropsychiatric disorders. Although this article uses the term probiotics in a general manner, it remains important to study probiotics at the strain level in most cases.

Review and Perspectives on Bifidobacterium lactis for Infants' and Children's Health.

The influence of microbiota dysbiosis in early life is increasingly recognized as a risk factor for the development of several chronic diseases later in life, including an increased risk of asthma, eczema, allergies, obesity, and neurodevelopmental disorders. The question whether the potential lifelong consequences of early life dysbiosis could be mitigated by restoring microbiota composition remains unresolved. However, the current evidence base suggests that protecting the normal development of the microbiome during this critical developmental window could represent a valuable public health strategy to curb the incidence of chronic and lifestyle-related diseases. Probiotic Bifidobacteria are likely candidates for this purpose in newborns and infants considering the natural dominance of this genus on microbiota composition in early life. Moreover, the most frequently reported microbiota composition alteration in association with newborn and infant diseases, including necrotizing enterocolitis and diarrhea, is a reduction in Bifidobacteria levels. Several studies have assessed the effects of B. animalis subsp. lactis strains in newborns and infants, but recent expert opinions recommend analyzing their efficacy at the strain-specific level. Hence, using the B94 strain as an example, this review summarizes the clinical evidence available in infants and children in various indications, discussing the safety and potential modes of actions while providing perspectives on the concept of "non-infant-type" probiotics for infants' health.

An Isolate of Streptococcus mitis Displayed In Vitro Antimicrobial Activity and Deleterious Effect in a Preclinical Model of Lung Infection.

Microbiota studies have dramatically increased over these last two decades, and the repertoire of microorganisms with potential health benefits has been considerably enlarged. The development of next generation probiotics from new bacterial candidates is a long-term strategy that may be more efficient and rapid with discriminative in vitro tests. Streptococcus strains have received attention regarding their antimicrobial potential against pathogens of the upper and, more recently, the lower respiratory tracts. Pathogenic bacterial strains, such as non-typable Haemophilus influenzae (NTHi), Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus), are commonly associated with acute and chronic respiratory diseases, and it could be interesting to fight against pathogens with probiotics. In this study, we show that a Streptococcus mitis (S. mitis) EM-371 strain, isolated from the buccal cavity of a human newborn and previously selected for promising anti-inflammatory effects, displayed in vitro antimicrobial activity against NTHi, P. aeruginosa or S. aureus. However, the anti-pathogenic in vitro activity was not sufficient to predict an efficient protective effect in a preclinical model. Two weeks of treatment with S. mitis EM-371 did not protect against, and even exacerbated, NTHi lung infection.

Comparing technology and regulatory landscape of probiotics as food, dietary supplements and live biotherapeutics.

Application of beneficial microorganisms as probiotics targets a broad range of intended uses, from maintaining health and supporting normal bodily functions to curing and preventing diseases. Currently, three main regulatory fields of probiotic products can be defined depending on their intended use: the more similar probiotic foods and probiotic dietary supplements, and live biotherapeutic products. However, it is not always straightforward to classify a probiotic product into one of these categories. The regulatory nuances of developing, manufacturing, investigating and applying each category of probiotic products are not universal, and not always apparent to those unfamiliar with the various global probiotic regulatory guidelines. Various global markets can be significantly different regarding legislation, possible claims, market value and quality requirements for the development and commercialization of probiotic products. Furthermore, different probiotic product categories are also linked with variable costs at different stages of product development. This review outlines the current landscape comparing probiotic foods, probiotic dietary supplements, and live biotherapeutics as probiotic products from a regulatory lens, focusing on product development, manufacturing and production, and clinical research agenda. The aim is to inform and promote a better understanding among stakeholders by outlining the expectations and performance for each probiotic product category, depending on their intended use and targeted geographical region.

Criteria to Qualify Microorganisms as "Probiotic" in Foods and Dietary Supplements.

Still relevant after 19 years, the FAO/WHO definition of probiotics can be translated into four simple and pragmatic criteria allowing one to conclude if specific strains of microorganisms qualify as a probiotic for use in foods and dietary supplements. Probiotic strains must be (i) sufficiently characterized; (ii) safe for the intended use; (iii) supported by at least one positive human clinical trial conducted according to generally accepted scientific standards or as per recommendations and provisions of local/national authorities when applicable; and (iv) alive in the product at an efficacious dose throughout shelf life. We provide clarity and detail how each of these four criteria can be assessed. The wide adoption of these criteria is necessary to ensure the proper use of the word probiotic in scientific publications, on product labels, and in communications with regulators and the general public.

Viral Infections, the Microbiome, and Probiotics.

Viral infections continue to cause considerable morbidity and mortality around the world. Recent rises in these infections are likely due to complex and multifactorial external drivers, including climate change, the increased mobility of people and goods and rapid demographic change to name but a few. In parallel with these external factors, we are gaining a better understanding of the internal factors associated with viral immunity. Increasingly the gastrointestinal (GI) microbiome has been shown to be a significant player in the host immune system, acting as a key regulator of immunity and host defense mechanisms. An increasing body of evidence indicates that disruption of the homeostasis between the GI microbiome and the host immune system can adversely impact viral immunity. This review aims to shed light on our understanding of how host-microbiota interactions shape the immune system, including early life factors, antibiotic exposure, immunosenescence, diet and inflammatory diseases. We also discuss the evidence base for how host commensal organisms and microbiome therapeutics can impact the prevention and/or treatment of viral infections, such as viral gastroenteritis, viral hepatitis, human immunodeficiency virus (HIV), human papilloma virus (HPV), viral upper respiratory tract infections (URTI), influenza and SARS CoV-2. The interplay between the gastrointestinal microbiome, invasive viruses and host physiology is complex and yet to be fully characterized, but increasingly the evidence shows that the microbiome can have an impact on viral disease outcomes. While the current evidence base is informative, further well designed human clinical trials will be needed to fully understand the array of immunological mechanisms underlying this intricate relationship.

Understanding mode of action can drive the translational pipeline towards more reliable health benefits for probiotics.

The different levels of knowledge described in a translational pipeline (the connection of molecular mechanisms with pre-clinical physiological and human health effects) are not complete for many probiotics. At present, we are not in a position to fully understand the mechanistic basis of many well established probiotic health benefits which, in turn, limits our ability to use mechanisms to predict which probiotics are likely to be effective in any given population. Here we suggest that this concept of a translation pipeline connecting mechanistic insights to probiotic efficacy can support the selection and production of improved probiotic products. Such a conceptual pipeline would also provide a framework for the design of clinical trials to convincingly demonstrate the benefit of probiotics to human health in well-defined subpopulations.

Health benefits of fermented foods: microbiota and beyond.

Fermented foods and beverages were among the first processed food products consumed by humans. The production of foods such as yogurt and cultured milk, wine and beer, sauerkraut and kimchi, and fermented sausage were initially valued because of their improved shelf life, safety, and organoleptic properties. It is increasingly understood that fermented foods can also have enhanced nutritional and functional properties due to transformation of substrates and formation of bioactive or bioavailable end-products. Many fermented foods also contain living microorganisms of which some are genetically similar to strains used as probiotics. Although only a limited number of clinical studies on fermented foods have been performed, there is evidence that these foods provide health benefits well-beyond the starting food materials.