In order to ensure precision in the use of probiotics, it is crucial to address the inherent heterogeneity present in probiotic strains, hosts, and their microbiomes. This comprehensive review aims ...to discuss the strategies necessary to mechanistically identify the most suitable probiotic strain of Bifidobacterium and/or Lactobacillus for targeting specific pathologies and comorbidities in individual patients. These strategies take into account the genetic and phenotypic characteristics of the strain, allowing for a personalized approach to probiotic selection.
The integration of multi-omics approaches, such as genomics, transcriptomics, metabolomics, and proteomics, plays a vital role in elucidating the intricate metabolic and intermicrobial interactions associated with individual probiotic strains. By employing these techniques, it becomes possible to reconstruct metabolic networks and study the cross-feeding and production of molecular effectors by probiotics. These findings hold significant potential in modulating the ecological balance of metabolic networks within the host's microbial consortia.
Specifically, this review will focus on the crucial role of Bifidobacteria and Lactobacillus as integral members of the human microbiota. It will delve into their potential as precision probiotics, aimed at preventing and treating various diseases.
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
(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
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 (
and
) 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
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.
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.
Weight gain is a well-known unwanted effect of valproic acid (VPA) therapy. Studies on VPA-associated changes of homeostatic hormones remain limited and controversial. Allopregnanolone (AP) is a ...circulating neuroactive steroid involved in modulation of behavioral activities whose serum levels are increased in obese children. The aim of the present study was to determine whether VPA therapy affects leptin and AP circulating levels in prepubertal girls with epilepsy. One-hundred and one patients were divided into four groups: epileptic patients with VPA-associated obesity (n = 21); lean epileptic patients under VPA therapy (n = 35); healthy obese children (n = 23), and healthy lean children (n = 22). Patients with VPA-associated obesity had significantly enhanced blood concentrations of AP (p = 0.001) and leptin (p = 0.007) than lean subjects. There were no differences in leptin and AP plasma levels between patients with VPA-associated obesity and obese controls (p = 0.45 and p = 0.10, respectively), as there were no differences between lean patients under VPA therapy and lean healthy controls (p = 0.06). In patients under VPA therapy, both plasma leptin and AP levels were significantly correlated with BMI (r = 0.074, p = 0.02, and r = 0.084, p = 0.01, respectively). Plasma leptin concentrations were not correlated with AP levels (r = 0.023, p = 0.13). In conclusion, a correlation between obesity and neuroactive steroids was shown. It remains to be established whether the increased circulating level of AP is a secondary effect of anxiolytic-sedative processes occurring in subjects with obesity-related emotional and behavioral anomalies, or plays a central role in determining abnormal eating behaviors.
