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.

Background/Objectives: There is growing interest in the benefits of probiotic supplementation during pregnancy and lactation, but evidence supporting the beneficial effects for mother–infant dyads remains scarce. This study assessed the effects of probiotic supplementation on infection frequency and immunity in pregnant women and infants, and on microbiome establishment during the first month of life. Methods: At 28 weeks of gestation, 180 healthy pregnant women were randomized to receive either a placebo (n = 90) or a probiotic supplement (n = 90), Prenatis™, containing 5 billion CFU/day of Lacticaseibacillus rhamnosus Rosell®-11 and Bifidobacterium bifidum HA-132. Results: There was a significantly lower number of women with one or more infections during the study in the probiotics group (8 vs. 18, p = 0.05) and a trend for a lower number of infections during pregnancy (primary outcome) in the probiotics group (p = 0.07). Regarding infants, a lower number of days with infections during the first month of life was observed in the probiotics group (4.7 days on average vs. 10.5 days, p = 0.03). The vaginal microbiota composition during pregnancy and after childbirth showed no significant differences between groups while the infants’ gut microbiome demonstrated a significantly higher abundance/prevalence of beneficial taxa in the probiotics group. The benefits conferred by probiotics were especially notable when considering birth by C-section. Probiotics promoted the vertical transmission of beneficial species and the induction of a highly interconnected microbiota, structured around key species. Conclusions: Probiotic supplementation during the third trimester of pregnancy and lactation is a valid strategy for conferring benefits to mothers and infants.

The microbiota-gut-brain axis (MGBA) has recently emerged as a useful model for the understanding of the onset and progression of neurodegenerative diseases (NDDs). Microbiome-based interventions using biotic supplements (probiotics, prebiotics, synbiotics, postbiotics) can modulate the MGBA and constitute relevant solutions to help reduce the risk of neurological changes associated with NDDs and manage symptoms. This narrative review provides a summary of the functioning of the MGBA and of its interactions with disease processes involved in the onset and progression of NDDs. Microbiome-based interventions and their mechanisms of action are reviewed, and important considerations for the design of interventions are discussed. Next, preclinical and clinical studies on the potential of microbiome-based interventions in Alzheimer’s disease (AD), Parkinson’s disease (PD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and Huntington’s disease (HD) are reviewed. Evidence related to biomarkers of pathology (e.g., beta-amyloid or alpha-synuclein protein depositions), neuroinflammation, and metabolic activity is summarized, along with emerging evidence for the improvement of clinical symptoms and disease trajectories. Overall, preclinical studies show that microbiome-based supplements have significant positive effects on mechanisms and pathways involved in the pathophysiology of NDDs. Clinical studies show that these interventions provide important benefits both in terms of biomarkers and clinical symptoms. However, evidence is limited in some key clinical areas, such as mental wellbeing in AD and cognition in PD, and for the management of clinical symptoms in ALS and HD overall. Gaps in knowledge and open questions as well as perspectives for future research are discussed.

Background: Recent advances linking gut dysbiosis with neurocognitive disorders such as Alzheimer’s disease (AD) suggest that the microbiota-gut-brain axis could be targeted for AD prevention, management, or treatment. Objective: We sought to identify probiotics that can delay Aβ-induced paralysis. Methods: Using C. elegans expressing human amyloid-β (Aβ) _1–42 in body wall muscles (GMC101), we assessed the effects of several probiotic strains on paralysis. Results: We found that Lacticaseibacillus rhamnosus HA-114 and Bacillus subtilis R0179, but not their supernatants or heat-treated forms, delayed paralysis and prolonged lifespan without affecting the levels of amyloid-β aggregates. To uncover the mechanism involved, we explored the role of two known pathways involved in neurogenerative diseases, namely mitophagy, via deletion of the mitophagy factor PINK-1, and fatty acid desaturation, via deletion of the Δ9 desaturase FAT-5. Pink-1 deletion in GMC101 worms did not modify the life-prolonging and anti-paralysis effects of HA-114 but reduced the protective effect of R0179 against paralysis without affecting its life-prolonging effect. Upon fat5 deletion in GMC101 worms, the monounsaturated C14:1 and C16:1 FAs conserved their beneficial effect while the saturated C14:0 and C16:0 FAs did not. The beneficial effects of R0179 on both lifespan and paralysis remained unaffected by fat-5 deletion, while the beneficial effect of HA-114 on paralysis and lifespan was significantly reduced. Conclusions: Collectively with clinical and preclinical evidence in other models, our results suggest that HA-114 or R0179 could be studied as potential therapeutical adjuncts in neurodegenerative diseases such as AD.

Helicobacter pylori (H. pylori) is a bacterial pathogen that infects half of the world population. While standard treatment was initially effective, eradication rates have declined over the last 20 to 30 years, and the use of adjuvants, such as probiotic supplements, has been suggested to improve efficacy. This review presents evidence supporting the use of Lacidofil^®, an established blend of two thoroughly characterized probiotic strains, as an adjuvant to standard therapy for H. pylori eradication. The microbiology and epidemiology of H. pylori infection as well as current approaches to diagnosis and treatment are summarized, and the roles of probiotics to support standard H. pylori treatment are outlined. Lacidofil^® and its component strains are described, and evidence from eight clinical trials supporting its efficacy is presented. H. pylori eradication rates were increased in participants receiving Lacidofil^® (90–100%) compared to controls (70–86.7%), and the incidence of side effects was decreased (e.g., antibiotic-associated diarrhea—Lacidofil^®: 0–13.6%; controls: 20–40.9%). Published summaries, including systematic reviews with meta-analysis and an umbrella review, are discussed. To expand on the discussion of clinical studies, in vivo and in vitro studies are reviewed, including studies using state-of-the-art molecular methods. They characterize Lacidofil^®’s mechanism of action and further support its efficacy as an adjuvant strategy for H. pylori eradication, side effect reduction, and return to gut microbiota homeostasis.

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.