Oral microbiota of patients with phenylketonuria: A nation-based cross-sectional study.

AIM: The oral microenvironment contributes to microbial composition and immune equilibrium. It is considered to be influenced by dietary habits. Phenylketonuria (PKU) patients, who follow a lifelong low-protein diet, exhibit higher prevalence of oral diseases such as periodontitis, offering a suitable model to explore the interplay between diet, oral microbiota and oral health. MATERIALS AND METHODS: We conducted 16S rDNA sequencing on saliva and subgingival plaque from 109 PKU patients (ages 6-68 years) and 114 age-matched controls and correlated oral microbial composition and dental health. RESULTS: PKU patients exhibited worse dental health, reduced oral microbial diversity and a difference in the abundance of specific taxa, especially Actinobacteriota species, compared to controls. PKU patients with poor periodontal health exhibited higher alpha diversity than the orally healthy ones, marked by high abundance of the genus Tannerella. Notably, the observed taxonomic differences in PKU patients with normal indices of decayed/missing/filled teeth, plaque control record, gingival bleeding index and periodontal screening and recording index generally differed from microbial signatures of periodontitis. CONCLUSIONS: PKU patients' reduced microbial diversity may be due to their diet's metabolic challenges disrupting microbial and immune balance, thus increasing oral inflammation. Higher alpha diversity in PKU patients with oral inflammation is likely related to expanded microbial niches.

Effects of Recombinant IL-13 Treatment on Gut Microbiota Composition and Functional Recovery after Hemisection Spinal Cord Injury in Mice.

In recent years, the gut-central nervous system axis has emerged as a key factor in the pathophysiology of spinal cord injury (SCI). Interleukin-13 (IL-13) has been shown to have anti-inflammatory and neuroprotective effects in SCI. The aim of this study was to investigate the changes in microbiota composition after hemisection injury and to determine whether systemic recombinant (r)IL-13 treatment could alter the gut microbiome, indirectly promoting functional recovery. The gut microbiota composition was determined by 16S rRNA gene sequencing, and correlations between gut microbiota alterations and functional recovery were assessed. Our results showed that there were no changes in alpha diversity between the groups before and after SCI, while PERMANOVA analysis for beta diversity showed significant differences in fecal microbial communities. Phylogenetic classification of bacterial families revealed a lower abundance of the Bacteroidales S24-7 group and a higher abundance of Lachnospiraceae and Lactobacillaceae in the post-SCI group. Systemic rIL-13 treatment improved functional recovery 28 days post-injury and microbiota analysis revealed increased relative abundance of Clostridiales vadin BB60 and Acetitomaculum and decreased Anaeroplasma, Ruminiclostridium_6, and Ruminococcus compared to controls. Functional assessment with PICRUSt showed that genes related to glyoxylate cycle and palmitoleate biosynthesis-I were the predominant signatures in the rIL-13-treated group, whereas sulfolactate degradation super pathway and formaldehyde assimilation-I were enriched in controls. In conclusion, our results indicate that rIL-13 treatment promotes changes in gut microbial communities and may thereby contribute indirectly to the improvement of functional recovery in mice, possibly having important implications for the development of novel treatment options for SCI.

Impact of High Salt-Intake on a Natural Gut Ecosystem in Wildling Mice.

The mammalian holobiont harbors a complex and interdependent mutualistic gut bacterial community. Shifts in the composition of this bacterial consortium are known to be a key element in host health, immunity and disease. Among many others, dietary habits are impactful drivers for a potential disruption of the bacteria-host mutualistic interaction. In this context, we previously demonstrated that a high-salt diet (HSD) leads to a dysbiotic condition of murine gut microbiota, characterized by a decrease or depletion of well-known health-promoting gut bacteria. However, due to a controlled and sanitized environment, conventional laboratory mice (CLM) possess a less diverse gut microbiota compared to wild mice, leading to poor translational outcome for gut microbiome studies, since a reduced gut microbiota diversity could fail to depict the complex interdependent networks of the microbiome. Here, we evaluated the HSD effect on gut microbiota in CLM in comparison to wildling mice, which harbor a natural gut ecosystem more closely mimicking the situation in humans. Mice were treated with either control food or HSD and gut microbiota were profiled using amplicon-based methods targeting the 16S ribosomal gene. In line with previous findings, our results revealed that HSD induced significant loss of alpha diversity and extensive modulation of gut microbiota composition in CLM, characterized by the decrease in potentially beneficial bacteria from Firmicutes phylum such as the genera Lactobacillus, Roseburia, Tuzzerella, Anaerovorax and increase in Akkermansia and Parasutterella. However, HSD-treated wildling mice did not show the same changes in terms of alpha diversity and loss of Firmicutes bacteria as CLM, and more generally, wildlings exhibited only minor shifts in the gut microbiota composition upon HSD. In line with this, 16S-based functional analysis suggested only major shifts of gut microbiota ecological functions in CLM compared to wildling mice upon HSD. Our findings indicate that richer and wild-derived gut microbiota is more resistant to dietary interventions such as HSD, compared to gut microbiota of CLM, which may have important implications for future translational microbiome research.

High-Salt Diet Induces Depletion of Lactic Acid-Producing Bacteria in Murine Gut.

Dietary habits are amongst the main factors that influence the gut microbiome. Accumulating evidence points to the impact of a high-salt diet (HSD) on the composition and function of the intestinal microbiota, immune system and disease. In the present study, we thus investigated the effects of different NaCl content in the food (0.03%/sodium deficient, 0.5%/control, 4% and 10% NaCl) on the gut microbiome composition in mice. The bacterial composition was profiled using the 16S ribosomal RNA (rRNA) gene amplicon sequencing. Our results revealed that HSD led to distinct gut microbiome compositions compared to sodium-deficient or control diets. We also observed significant reduction in relative abundances of bacteria associated with immuno-competent short-chain fatty acid (SCFA) production (Bifidobacterium, Faecalibaculum, Blautia and Lactobacillus) in HSD-fed mice along with significant enrichment of Clostridia, Alistipes and Akkermansia depending on the sodium content in food. Furthermore, the predictive functional profiling of microbial communities indicated that the gut microbiota found in each category presents differences in metabolic pathways related to carbohydrate, lipid and amino acid metabolism. The presented data show that HSD cause disturbances in the ecological balance of the gastrointestinal microflora primarily through depletion of lactic acid-producing bacteria in a dose-dependent manner. These findings may have important implications for salt-sensitive inflammatory diseases.

Guts within guts: the microbiome of the intestinal helminth parasite Ascaris suum is derived but distinct from its host.

BACKGROUND: Intestinal helminths are extremely prevalent among humans and animals. In particular, intestinal roundworms affect more than 1 billion people around the globe and are a major issue in animal husbandry. These pathogens live in intimate contact with the host gut microbiota and harbor bacteria within their own intestines. Knowledge of the bacterial host microbiome at the site of infection is limited, and data on the parasite microbiome is, to the best of our knowledge, non-existent. RESULTS: The intestinal microbiome of the natural parasite and zoonotic macropathogen, Ascaris suum was analyzed in contrast to the diversity and composition of the infected host gut. 16S sequencing of the parasite intestine and host intestinal compartments showed that the parasite gut has a significantly less diverse microbiome than its host, and the host gut exhibits a reduced microbiome diversity at the site of parasite infection in the jejunum. While the host's microbiome composition at the site of infection significantly determines the microbiome composition of its parasite, microbial signatures differentiate the nematodes from their hosts as the Ascaris intestine supports the growth of microbes that are otherwise under-represented in the host gut. CONCLUSION: Our data clearly indicate that a nematode infection reduces the microbiome diversity of the host gut, and that the nematode gut represents a selective bacterial niche harboring bacteria that are derived but distinct from the host gut. Video Abstract.