Intra-species Genomic and Physiological Variability Impact Stress Resistance in Strains of Probiotic Potential

Abstract

Large-scale microbiome studies have established that most of the diversity contained in the gastrointestinal tract is represented at the strain level; however, exhaustive genomic and physiological characterization of human isolates is still lacking. With increased use of probiotics as interventions for gastrointestinal disorders, genomic and functional characterization of novel microorganisms becomes essential. In this study, we explored the impact of strain-level genomic variability on bacterial physiology of two novel human Lactobacillus rhamnosus strains (AMC143 and AMC010) of probiotic potential in relation to stress resistance. The strains showed differences with known probiotic strains (L. rhamnosus GG, Lc705, and HN001) at the genomic level, including nucleotide polymorphisms, mutations in non-coding regulatory regions, and rearrangements of genomic architecture. Transcriptomics analysis revealed that gene expression profiles differed between strains when exposed to simulated gastrointestinal stresses, suggesting the presence of unique regulatory systems in each strain. In vitro physiological assays to test resistance to conditions mimicking the gut environment (acid, alkali, and bile stress) showed that growth of L. rhamnosus AMC143 was inhibited upon exposure to alkaline pH, while AMC010 and control strain LGG were unaffected. AMC143 also showed a significant survival advantage compared to the other strains upon bile exposure. Reverse transcription qPCR targeting the bile salt hydrolase gene (bsh) revealed that AMC143 expressed bsh poorly (a consequence of a deletion in the bsh promoter and truncation of bsh gene in AMC143), while AMC010 had significantly higher expression levels than AMC143 or LGG. Insertional inactivation of the bsh gene in AMC010 suggested that bsh could be detrimental to bacterial survival during bile stress. Together, these findings show that coupling of classical microbiology with functional genomics methods for the characterization of bacterial strains is critical for the development of novel probiotics, as variability between strains can dramatically alter bacterial physiology and functionality.

Technological characterization of vaginal probiotic lactobacilli: resistance to osmotic stress and strains compatibility

“…Arnold et al . () have recently showed that intra‐species genomic and physiological variability impacts stress resistance in strains of probiotic potential, but, there are no studies describing which mechanisms are related to the stress resistance in strains isolated from the urogenital tract, and this aspect supports the originality of our results.…”

“…Senan et al (2014) have shown different stress-responsive gene sets in L. helveticus that are required to adapt to gut and dairy niches, indicating a niche adaptation. Arnold et al (2018) have recently showed that intra-species genomic and physiological variability impacts stress resistance in strains of probiotic potential, but, there are no studies describing which mechanisms are related to the stress resistance in strains isolated from the urogenital tract, and this aspect supports the originality of our results.…”

Prebiotics for Lactose Intolerance: Variability in Galacto-Oligosaccharide Utilization by Intestinal Lactobacillus rhamnosus

“…The impact that probiotics have on their host is directly related to their physiology, often highly variable between strains. In order for a microorganism to act as a probiotic, it must first survive the stresses associated with the gastrointestinal tract [ 30 ], a capability that is highly variable between strains [ 31 , 32 , 33 ]. Similarly, the mechanisms by which probiotics provide a benefit vary between strains, including carbohydrate fermentation [ 9 ], an important feature of probiotics [ 34 ].…”

“…Research studies have determined that the majority of the intestinal diversity is present at the species and strain levels [ 33 , 35 , 36 ]. In the gastrointestinal tract, GOS are metabolized by bacterial β-galactosidases and β-glucosidases, though mechanisms for GOS transport and utilization vary between species and strains [ 37 ].…”

Antibacterial Effect of Zinc Oxide-Based Nanomaterials on Environmental Biodeteriogens Affecting Historical Buildings

“…Surprisingly, A. spanius TC1 and A. spanius TC7 showed different behavior when treated with ZnO-NRs, highlighting the presence of intra-species differences between the two strains. Indeed, as reported in biodiversity studies of several bacterial species, intra-species analysis revealed extensive variation between isolates, both at the genotypic and phenotypic level [41,42].…”