Although research on the role of the gut microbiota (GM) in human health has sharply increased in recent years, what a “healthy” gut microbiota is and how it responds to major stressors is still difficult to establish. In particular, anticancer chemotherapy is known to have a drastic impact on the microbiota structure, potentially hampering its recovery with serious long-term consequences for patients’ health. However, the distinguishing features of gut microbiota recovery and non-recovery processes are not yet known. In this narrative review, we first investigated how gut microbiota layouts are affected by anticancer chemotherapy and identified potential gut microbial recovery signatures. Then, we discussed microbiome-based intervention strategies aimed at promoting resilience, i.e., the rapid and complete recovery of a healthy gut microbial network associated with a better prognosis after such high-impact pharmacological treatments.
The human gut is home to trillions of microorganisms that influence several aspects of our health. This dense microbial community targets almost all dietary polysaccharides and releases multiple metabolites, some of which have physiological effects on the host. A healthy equilibrium between members of the gut microbiota, its microbial diversity, and their metabolites is required for intestinal health, promoting regulatory or anti-inflammatory immune responses. In contrast, the loss of this equilibrium due to antibiotics, low fiber intake, or other conditions results in alterations in gut microbiota composition, a term known as gut dysbiosis. This dysbiosis can be characterized by a reduction in health-associated microorganisms, such as butyrate-producing bacteria, enrichment of a small number of opportunistic pathogens, or a reduction in microbial diversity. Bifidobacterium species are key species in the gut microbiome, serving as primary degraders and contributing to a balanced gut environment in various ways. Colonization resistance is a fundamental property of gut microbiota for the prevention and control of infections. This community competes strongly with foreign microorganisms, such as gastrointestinal pathogens, antibiotic-resistant bacteria, or even probiotics. Resistance to colonization is based on microbial interactions such as metabolic cross-feeding, competition for nutrients, or antimicrobial-based inhibition. These interactions are mediated by metabolites and metabolic pathways, representing the inner workings of the gut microbiota, and play a protective role through colonization resistance. This review presents a rationale for how microbial interactions provide resistance to colonization and gut dysbiosis, highlighting the protective role of Bifidobacterium species.
Aim: The “gut-joint” axis is suspected to be involved in the pathophysiology of osteoarthritis (OA). The present study aims at investigating the potential of lipoproteins (Lpps) secreted by Bifidobacterium longum to alleviate OA progression in the rat.
Methods: Experimental OA was induced in rats harbouring Schaedler Flora maintained in SPF conditions. Two weeks post-injection, 20 rats were randomized to water (n = 10) or 0.3 mg/L Lpps solution (n = 10). Weight and food intake were monitored for 6 weeks. At sacrifice, joints were scored using macroscopic and histological criteria. Serum LPS, Schaedler flora as well as selected intestinal bacteria were analyzed.
Results: Lpps intake prevents OA progression. The protected rats showed a significant increase in lactobacilli along the intestine as well as in Mucispirillum schaedleri in the colon and a significant decrease in Parabacteroides goldsteini and Akkermansia in caecum and colon, respectively. There was no significant difference in serum lipopolysaccharide or bacteria translocating in Peyer's patches. Labelled Lpps were not detected in bone marrow of the OA joint. The principal component analysis points out that OA prevention is primarily associated with bacteria involved in the tryptophane degradation pathway and SCFA formation.
Conclusion: In rats deprived of bifidobacteria, intake of B.longum Lpps prevented OA development and modulated the intestinal microbiome with a possible impact on the bacterial end-products. The link between Lpps and the gut microbial metabolome warrants further investigation.
Delirium is a clinical syndrome characterized by an acute change in attention, awareness and cognition with fluctuating course, frequently observed in older patients during hospitalization for acute medical illness or after surgery. Its pathogenesis is multifactorial and still not completely understood, but there is general consensus on the fact that it results from the interaction between an underlying predisposition, such as neurodegenerative diseases, and an acute stressor acting as a trigger, such as infection or anesthesia. Alterations in brain insulin sensitivity and metabolic function, increased blood-brain barrier permeability, neurotransmitter imbalances, abnormal microglial activation and neuroinflammation have all been involved in the pathophysiology of delirium. Interestingly, all these mechanisms can be regulated by the gut microbiota, as demonstrated in experimental studies investigating the microbiota-gut-brain axis in dementia. Aging is also associated with profound changes in gut microbiota composition and functions, which can influence several aspects of disease pathophysiology in the host. This review provides an overview of the emerging evidence linking age-related gut microbiota dysbiosis with delirium, opening new perspectives for the microbiota as a possible target of interventions aimed at delirium prevention and treatment.
Aim: Bifidobacterium longum subsp. infantis uses a glycoside hydrolase (GH) family 42 β-galactosidase (BiBga42A) for hydrolyzing lacto-N-tetraose (LNT), which is the most abundant core structure of human milk oligosaccharides (HMOs). As such, BiBga42A represents one of the pivotal enzymes underpinning the symbiosis between bifidobacteria and breastfed infants. Despite its importance, the structural basis underlying LNT hydrolysis by BiBga42A is not understood. Moreover, no substrate-complexed structures are available to date for GH42 family members.
Methods: X-ray crystallography was used to determine the structures of BiBga42A in the apo- and liganded forms. The roles of the amino acid residues that were presumed to be involved in catalysis and substrate recognition were examined by a mutational study, in which kinetic parameters of each mutant were determined using 4-nitrophenyl-β-D-galactoside, lacto-N-biose I, LNT, and lacto-N-neotetraose (LNnT) as substrates. Conservation of those amino acid residues was examined among structure-determined GH42 β-galactosidases.
Results: Crystal structures of the wild-type enzyme complexed with glycerol, the E160A/E318A double mutant complexed with galactose (Gal), and the E318S mutant complexed with LNT were determined at 1.7, 1.9, and 2.2 Å resolutions, respectively. The LNT molecule (excluding the Gal moiety at subsite +2) bound to the E318S mutant is recognized by an extensive hydrogen bond network and several hydrophobic interactions. The non-reducing end Gal moiety of LNT adopts a slightly distorted conformation and does not overlap well with the Gal molecule bound to the E160A/E318A mutant. Twelve of the sixteen amino acid residues responsible for LNT recognition and catalysis in BiBga42A are conserved among all homologs including β-1,6-1,3-galactosidase (BlGal42A) from Bifidobacterium animalis subsp. lactis.
Conclusion: BlGal42A is active on 3-β-galactobiose similarly to BiBga42A but is inactive on LNT. Interestingly, we found that the entrance of the catalytic pocket of BlGal42A is narrower than that of BiBga42A and seems not easily accessible from the solvent side due to the presence of two bulky amino acid side chains. The specificity difference may reflect the structural difference between the two enzymes.
Aim: To identify novel genera amongst mycobacteriophages (MP) and verify a hypothesised correlation between the taxonomy set by the International Committee on Taxonomy of Viruses (ICTV) and the National Centre for Biotechnology Information (NCBI) with that of the Actinobacteriophage Database, which may help formalise subcluster assignment.
Methods: A dataset of 721 MP genomes was analysed using VIRIDIC, a nucleotide alignment-based software that predicts genus assignments. Potentially novel genera were analysed using Gegenees and VICTOR, respectively. These genera were then compared to the subclusters assigned by the Actinobacteriophage Database to verify a hypothesis that one genus can be assigned to one subcluster (i.e., the genus-subcluster hypothesis).
Results: Initially, when comparing the current genus classifications of the 721 MP dataset to the Actinobacteriophage database subcluster assignments, 83.3% of subclusters supported the genus-subcluster hypothesis. Following the sequential VIRIDIC, Gegenees and VICTOR analyses, a total of 20 novel genera were identified based on a ≥ 70% and ~ 50% similarity threshold for VIRIDIC and Gegenees, respectively, and a monophyletic nature in the VICTOR output. Interestingly, these criteria also appear to support the creation of 13 novel subclusters, which would increase the support for the genus-subcluster hypothesis to 97.6%.
Conclusion: The link between genus and subcluster classifications appears robust, as most subclusters can be assigned a single genus and vice versa. By relating the taxonomic and clustering classification systems, they can be easily kept up to date to best reflect MP diversity, which could aid the rapid selection of related (or diverse) phages for research, therapeutic and diagnostic purposes.
Aim: Dietary fibre is important for shaping gut microbiota. The aim of this pilot study was to investigate the impact of dietary fibres on pathogen performance in the presence of gut microbiota.
Methods: In an ex vivo gut model, pooled faecal samples were spiked with a cocktail of representative gastrointestinal pathogens and fermented with yeast β-glucan for 24 hours, after which 16S rRNA amplicon sequencing and short-chain and branched-chain fatty acid (SCFA and BCFA) analyses were performed. In addition, oat β-glucan, arabinoxylan, yeast β-glucan, and galactooligosaccharides were each tested against individual representative pathogens and pathogen growth was assessed via qPCR. Glucose served as a control carbon source.
Results: Based on 16S rRNA amplicon sequencing, yeast β-glucan selected for higher proportions of Bacteroides (P = 0.0005, ~6 fold) and Clostridia (P = 0.005, ~3.6 fold) while species of Escherichia/Shigella (P = 0.021, ~2.8 fold) and Lactobacillus (P = 0.007, ~ 15.7-fold) were higher in glucose. Pathogen relative abundance did not differ between glucose and yeast β-glucan. In the absence of pathogens, higher production of BCFAs (P = 0.002) and SCFAs (P = 0.002) fatty acids was observed for fibre group(s). For individual pathogens, yeast β-glucan increased growth of Escherichia coli, Salmonella typhimurium, and Listeria monocytogenes (P < 0.05), arabinoxylan increased S. typhimurium (P < 0.05). Tested fibres decreased vancomycin-resistant Enterococcus faecium (P < 0.05), with yeast β-glucan causing a 1-log reduction (P < 0.01), while galactooligosaccharides decreased L. monocytogenes (P < 0.05).
Conclusion: Tested fibres differentially influenced the growth of pathogens, but yeast β-glucan could represent a dietary strategy to help limit vancomycin-resistant enterococci (VRE) expansion in the gut.
Background: At birth, the human intestine is colonized by a complex community of microorganisms known as gut microbiota. These complex microbial communities that inhabit the gut microbiota are thought to play a key role in maintaining host physiological homeostasis. For this reason, correct colonization of the gastrointestinal tract in the early stages of life could be fundamental for human health. Furthermore, alterations of the infant microbiota are correlated with the development of human inflammatory diseases and disorders. In this context, the possible relationships between intestinal microbiota and body composition during infancy are of great interest.
Methods: In this study, we have performed a pilot study based on 16S rRNA gene profiling and metagenomic approaches on repeatedly measured data on time involving a cohort of 41 Italian newborns, which is aimed to investigate the possible correlation between body fat mass percentage (FM%) and the infant gut microbiota composition.
Results and conclusion: The taxonomical analysis of the stool microbiota of each infant included in the cohort allowed the identification of a specific correlation between intestinal bacteria, such as Bifidobacterium and Veillonella, and the increase in FM%. Moreover, the analysis of the infant microbiome’s metabolic capabilities suggested that the intestinal microbiome functionally impacts the human host and its possible influence on host physiology.
The gut microbiome has received a crescendo of attention in recent years due to myriad influences on human pathophysiology, including cancer. Anticancer therapy research is constantly looking for new hints to improve response to therapy while reducing the risk of relapse. In this scenario, Bifidobacterium, which inhabits the gut microbial ecosystem (especially that of children) and is considered a health-associated microbe, has emerged as a key target to assist anticancer treatments for a better prognosis. However, some researchers have recently hypothesized an unfavorable role of Bifidobacterium spp. in anticancer immunochemotherapy, leading to some confusion in the field. This narrative review summarizes the current knowledge on the role of Bifidobacterium spp. in relation to anticancer treatments, discussing the pros and cons of its presence in the gut microbiome of cancer patients. The current intervention strategies based on the administration of probiotic strains of Bifidobacterium are then discussed. Finally, the need to conduct further studies, especially functional ones, is underlined to provide robust experimental evidence, especially on the underlying molecular mechanisms, and thus resolve the controversies on this microbe for the long-term success of immunochemotherapy.