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It is well established that host-associated microbial communities can interfere with the colonization and establishment of microbes of foreign origins, a phenomenon often referred to as bacterial interference or colonization resistance. However, due to the complexity of the indigenous microbiota, it has been extremely difficult to elucidate the community colonization resistance mechanisms and identify the bacterial species involved. In a recent study, we have established an in vitro mice oral microbial community (O-mix) and demonstrated its colonization resistance against an Escherichia coli strain of mice gut origin. In this study, we further analyzed the community structure of the O-mix by using a dilution/regrowth approach and identified the bacterial species involved in colonization resistance against E. coli. Our results revealed that, within the O-mix there were three different types of bacterial species forming unique social structure. They act as 'Sensor', 'Mediator' and 'Killer', respectively, and have coordinated roles in initiating the antagonistic action and preventing the integration of E. coli. The functional role of each identified bacterial species was further confirmed by E. coli-specific responsiveness of the synthetic communities composed of different combination of the identified players. The study reveals for the first time the sophisticated structural and functional organization of a colonization resistance pathway within a microbial community. Furthermore, our results emphasize the importance of 'Facilitation' or positive interactions in the development of community-level functions, such as colonization resistance.

The gastrointestinal (GI) tract is home to trillions of microbes. Within the same GI tract, substantial differences in the bacterial species that inhabit the oral cavity and intestinal tract have been noted. While the influence of host environments and nutritional availability in shaping different microbial communities is widely accepted, we hypothesize that the existing microbial flora also plays a role in selecting the bacterial species that are being integrated into the community. In this study, we used cultivable microbial communities isolated from different parts of the GI tract of mice (oral cavity and intestines) as a model system to examine this hypothesis. Microbes from these two areas were harvested and cultured using the same nutritional conditions, which led to two distinct microbial communities, each with about 20 different species as revealed by PCR-based denaturing gradient gel electrophoresis analysis. In vitro community competition assays showed that the two microbial floras exhibited antagonistic interactions toward each other. More interestingly, all the original isolates tested and their closely related species displayed striking community preferences: They persisted when introduced into the bacterial community of the same origin, while their viable count declined more than three orders of magnitude after 4 days of coincubation with the microbial flora of foreign origin. These results suggest that an existing microbial community might impose a selective pressure on incoming foreign bacterial species independent of host selection. The observed inter-flora interactions could contribute to the protective effect of established microbial communities against the integration of foreign bacteria to maintain the stability of the existing communities.

Within the same human gastrointestinal tract, substantial differences in the bacterial species that inhabit oral cavity and intestinal tract have been noted. Previous research primarily attributed the differences to the influences of host environments and nutritional availabilities ("host habitat" effect). Our recent study indicated that, other than the host habitat effect, an existing microbial community could impose a selective pressure on incoming foreign bacterial species independent of host-mediated selection ("community selection" effect). In this study, we employed in vitro microbial floras representing microorganisms that inhabit the oral cavities and intestinal tract of mice in combination with Escherichia coli as a model intestinal bacterium and demonstrated that E. coli displays a striking community preference. It thrived when introduced into the intestinal microbial community and survived poorly in the microbial flora of foreign origin (oral community). A more detailed examination of this phenomenon showed that the oral community produced oxygen-free radicals in the presence of wild-type E. coli while mutants deficient in lipopolysaccharides (LPS) did not trigger significant production of these cell-damaging agents. Furthermore, mutants of E. coli defective in the oxidative stress response experienced a more drastic reduction in viability when cocultivated with the oral flora, while the exogenous addition of the antioxidant vitamin C was able to rescue it. We concluded that the oral-derived microbial community senses the E. coli LPS and kills the bacterium with oxygen-free radicals. This study reveals a new mechanism of community invasion resistance employed by established microflora to defend their domains.

One major challenge to studying human microbiome and its associated diseases is the lack of effective tools to achieve targeted modulation of individual species and study its ecological function within multispecies communities. Here, we show that C16G2, a specifically targeted antimicrobial peptide, was able to selectively kill cariogenic pathogen Streptococcus mutans with high efficacy within a human saliva-derived in vitro oral multispecies community. Importantly, a significant shift in the overall microbial structure of the C16G2-treated community was revealed after a 24-h recovery period: several bacterial species with metabolic dependency or physical interactions with S. mutans suffered drastic reduction in their abundance, whereas S. mutans' natural competitors, including health-associated Streptococci, became dominant. This study demonstrates the use of targeted antimicrobials to modulate the microbiome structure allowing insights into the key community role of specific bacterial species and also indicates the therapeutic potential of C16G2 to achieve a healthy oral microbiome.

Mouth breathing induces a series of diseases, while the influence on microbiota of oral cavity and salivary proteins remains unknown. In this study, for the first time, profiles of oral–nasal–pharyngeal microbiota among mouth-breathing children (MB group, n = 10) were compared with paired nose-breathing children (NB group, n = 10) using 16S ribosomal DNA (rDNA) (V3–V4 region) high-throughput sequencing. The differentially expressed salivary proteins were revealed using label-free quantification (LFQ) method, and their associations with bacterial abundance were measured by canonical correspondence analysis (CCA). The overall bacterial profiles differed between the two groups, and the differences were related to the duration of mouth breathing. The diversity of oral–pharyngeal microbiota was significantly higher, and the nasal–pharyngeal species tended to be consistent (unweighted UniFrac, p = 0.38) in the MB group. Opportunistic pathogens were higher in relative abundance as follows: Acinetobacter in the anterior supragingival plaque, Neisseria in unstimulated saliva, Streptococcus pneumoniae in the pharynx, and Stenotrophomonas in the nostrils. The expression level of oxidative-stress-related salivary proteins (lactoylglutathione lyase and peroxiredoxin-5) were upregulated, while immune-related proteins (integrin alpha-M and proteasome subunit alpha type-1) were downregulated in MB group. The differentially expressed proteins were associated with specific bacteria, indicating their potentials as candidate biomarkers for the diagnosis, putatively early intervention, and therapeutic target of mouth breathing. This study showed that mouth breathing influences the oral–nasal–pharyngeal microbiota and enriches certain pathogens, accompanied with the alterations in the salivary environment. Further research on the pathological mechanisms and dynamic changes in longitudinal studies are warranted. [ABSTRACT FROM AUTHOR]

Streptococcus mutans is an oral species closely associated with dental caries. As an early oral colonizer, S. mutans utilizes interspecies coaggregation to promote the colonization of subsequent species and affect polymicrobial pathogenesis. Previous studies have confirmed several adhering partner species of S. mutans , including Candida albicans and Fusobacterium nucleatum. In this study, we discovered new intergeneric co-adherence between S. mutans and the saliva isolate Streptococcus agalactiae (GBS-SI101). Research shows that GBS typically colonizes the human gastrointestinal and vaginal tracts. It is responsible for adverse pregnancy outcomes and life-threatening infections in neonates and immunocompromised people. Our results revealed that GtfB and GtfC of S. mutans , which contributed to extracellular polysaccharide synthesis, promoted coaggregation of S. mutans with GBS-SI101. In addition, oral streptococci, including Streptococcus sanguinis, Streptococcus gordonii and S. mutans , barely inhibited the growth of GBS-SI101. This study indicated that S. mutans could help GBS integrate into the Streptococcus- associated oral polymicrobial community and become a resident species in the oral cavity, increasing the risk of oral infections. [ABSTRACT FROM AUTHOR]