Background: Emerging evidence suggests that the maternal microbiome plays a crucial role in shaping fetal neurodevelopment, immune programming, and metabolic health. Dysbiosis during pregnancy—whether gastrointestinal, oral, or vaginal—can significantly influence pregnancy outcomes and long-term child health. Materials and Methods: The search was performed using databases such as PubMed, Scopus, and Google Scholar including research published from January 2000 to January 2025. The keywords used were “Fetal Programming”, “ Maternal Immune Activation”, “Maternal microbiome”, “Microbiota–Gut–Brain Axis”, and “Pregnancy Dysbiosis”. Results: The maternal microbiome undergoes substantial changes during pregnancy, with alterations in microbial diversity and function linked to conditions such as gestational diabetes, obesity, and preeclampsia. Pregnancy-related dysbiosis has been associated with adverse neurodevelopmental outcomes, including an increased risk of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and cognitive impairments in offspring. Conclusions: Understanding the intricate relationship between maternal microbiota and fetal health is essential for developing targeted interventions. Personalized microbiome-based strategies, including dietary modifications and probiotic supplementation, hold promise in optimizing pregnancy outcomes and promoting health in offspring.

Celiac disease (CeD) is an autoimmune disease with a strong association with human leukocyte antigen (HLA), characterized by the production of specific autoantibodies and immune-mediated enterocyte killing. CeD is a unique autoimmune condition, as it is the only one in which the environmental trigger is known: gluten, a storage protein present in wheat, barley, and rye. How and when the loss of tolerance of the intestinal mucosa to gluten occurs is still unknown. This event, through the activation of adaptive immune responses, enhances epithelial cell death, increases the permeability of the epithelial barrier, and induces secretion of pro-inflammatory cytokines, resulting in the transition from genetic predisposition to the actual onset of the disease. While the role of gastrointestinal infections as a possible trigger has been considered on the basis of a possible mechanism of antigen mimicry, a more likely alternative mechanism appears to involve a complex disruption of the gastrointestinal microbiota ecosystem triggered by infections, rather than the specific effect of a single pathogen on intestinal mucosal homeostasis. Several lines of evidence show the existence of intestinal dysbiosis that precedes the onset of CeD in genetically at-risk subjects, characterized by the loss of protective bacterial elements that both epigenetically and functionally can influence the response of the intestinal epithelium leading to the loss of gluten tolerance. We have conducted a literature review in order to summarize the current knowledge about the complex and in part still unraveled dysbiosis that precedes and accompanies CeD and present some exciting new data on how this dysbiosis might be prevented and/or counteracted. The literature search was conducted on PubMed.gov in the time frame 2010 to March 2024 utilizing the terms “celiac disease and microbiota”, “celiac disease and microbiome”, and “celiac disease and probiotics” and restricting the search to the following article types: Clinical Trials, Meta-Analysis, Review, and Systematic Review. A total of 364 papers were identified and reviewed. The main conclusions of this review can be outlined as follows: (1) quantitative and qualitative changes in gut microbiota have been clearly documented in CeD patients; (2) intestinal microbiota’s extensive and variable interactions with enterocytes, viral and bacterial pathogens and even gluten combine to impact the inflammatory immune response to gluten and the loss of gluten tolerance, ultimately affecting the pathogenesis, progression, and clinical expression of CeD; (3) gluten-free diet fails to restore the eubiosis of the digestive tract in CeD patients, and also negatively affects microbial homeostasis; (4) new tools allowing targeted microbiota therapy, such as the use of probiotics (a good example being precision probiotics like the novel strain of B. vulgatus (20220303-A2) begin to show exciting potential applications.

Antibiotics are one of the greatest scientific achievements of modern medicine, but excessive use is creating challenges for the future of medicine. Antibiotic resistance (AR) is thought to cause changes in bowel habits and an increased risk of gastroenteritis, but it may also increase the risk of overweight, obesity, autoimmune and atopic diseases, and a low response to vaccines and cancer, likely mediated by antibiotic-induced gut dysbiosis. Probiotic add-on therapy could partially prevent antibiotic-induced gut dysbiosis, but their antibiotic sensitivity features likely limits this potential. The EFSA (European Food Safety Authority) guidelines consider the use of probiotics whose antibiotic-resistant profile could be transferable an important hazard. Recently, a strain of B. breve (PRL2020) has shown to be resistant to amoxicillin and amoxicillin-clavulanate (AC) by applying the microdilution protocol according EFSA guidelines. After verifying that horizontal gene transfer is unlikely to take place, this feature suggests its concomitant use with these specific antibiotics. The results of our tests demonstrated that the strain PRL2020 is indeed endowed with amoxicillin- and AC-resistant properties and that it is also insensitive to ampicillin. In-depth analysis of the annotated genome sequence of B. breve PRL2020 was employed to query the Comprehensive Antibiotic Resistance Database (CARD) using Resistance Gene Identifier (RGI) software (version 5.2.1). The similarity among the AR determinants found was studied through nucleotide sequence alignment, and it was possible to verify not only the absence of genes explaining these features in the flanking regions but also the presence of genetic sequences (rpoB and erm(X)) putatively responsible for rifampicin and erythromycin resistance. Both features are not phenotypically expressed, and for these antibiotics, the strain is within the EFSA limits. Analysis of the flanking regions of these genes revealed possible mobile elements upstream and downstream only in the case of the erm(X) gene, but the features of the Insertion Sequences (IS) are described as not to cause horizontal transfer. Our findings on strain PRL2020 demonstrate that its AR profile is compatible with antibiotics when taken with the aim of reducing the risk of dysbiosis.

Autism spectrum disorder (ASD) is often associated with several intestinal and/or metabolic disorders as well as neurological manifestations such as epilepsy (ASD-E). Those presenting these neuropathological conditions share common aspects in terms of gut microbiota composition. The use of microbiota intervention strategies may be an approach to consider in the management of these cases. We describe the case of a 17-year-old girl affected by ASD, reduced growth, neurological development delay, mutations in the PGM1 and EEF1A2 genes (in the absence of clinically manifested disease) and, intestinal disorders such as abdominal pain and diarrhea associated with weight loss. As she demonstrated poor responsiveness to the therapies provided, we attempted two specific dietary patterns: a ketogenic diet, followed by a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet, with the aim of improving her neurological, metabolic, and intestinal symptoms through modulation of the gut microbiota’s composition. The ketogenic diet (KD) provided a reduction in Firmicutes, Bacteroidetes, and Proteobacteria. Although her intestinal symptoms improved, KD was poorly tolerated. On the other hand, the passage to a low FODMAPs diet produced a significant improvement in all neurological, intestinal, and metabolic symptoms and was well-tolerated. The following gut microbiota analysis showed reductions in Actinobacteria, Firmicutes, Lactobacilli, and Bifidobacteria. The alpha biodiversity was consistently increased and the Firmicutes/Bacteroidetes ratio decreased, reducing the extent of fermentative dysbiosis. Gut microbiota could be a therapeutic target to improve ASD-related symptoms. Further studies are needed to better understand the correlation between gut microbiota composition and ASD, and its possible involvement in the physiopathology of ASD.

The discovery of immune checkpoints (CTLA-4, PD-1, and PD-L1) and their impact on the prognosis of oncological diseases have paved the way for the development of revolutionary oncological treatments. These treatments do not combat tumors with drugs “against” cancer cells but rather support and enhance the ability of the immune system to respond directly to tumor growth by attacking the cancer cells with lymphocytes. It has now been widely demonstrated that the presence of an adequate immune response, essentially represented by the number of TILs (tumor-infiltrating lymphocytes) present in the tumor mass decisively influences the response to treatments and the prognosis of the disease. Therefore, immunotherapy is based on and cannot be carried out without the ability to increase the presence of lymphocytic cells at the tumor site, thereby limiting and nullifying certain tumor evasion mechanisms, particularly those expressed by the activity (under positive physiological conditions) of checkpoints that restrain the response against transformed cells. Immunotherapy has been in the experimental phase for decades, and its excellent results have made it a cornerstone of treatments for many oncological pathologies, especially when combined with chemotherapy and radiotherapy. Despite these successes, a significant number of patients (approximately 50%) do not respond to treatment or develop resistance early on. The microbiota, its composition, and our ability to modulate it can have a positive impact on oncological treatments, reducing side effects and increasing sensitivity and effectiveness. Numerous studies published in high-ranking journals confirm that a certain microbial balance, particularly the presence of bacteria capable of producing short-chain fatty acids (SCFAs), especially butyrate, is essential not only for reducing the side effects of chemoradiotherapy treatments but also for a better response to immune treatments and, therefore, a better prognosis. This opens up the possibility that favorable modulation of the microbiota could become an essential complementary treatment to standard oncological therapies. This brief review aims to highlight the key aspects of using precision probiotics, such as Clostridium butyricum, that produce butyrate to improve the response to immune checkpoint treatments and, thus, the prognosis of oncological diseases.