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Page 6 of 13 Martin et al. Microbiome Res Rep 2023;2:17 https://dx.doi.org/10.20517/mrr.2023.10

[37]
butyrate . Several Bifidobacterium species have been shown to promote BPB growth and butyrate
production. This process is both strain- and substrate-dependent. For example, Faecalibacterium
prausnitzii, a dominant BPB, can cross-feed with Bifidobacterium adolescentis and Bifidobacterium
[100]
catenulatum when using inulin as a substrate, both in vitro and in vivo . In addition, during HMO
utilization, B. infantis enhanced Anaerostipes caccae growth via HMO degradation products, as well as
acetate and lactate production .
[44]
However, cross-feeding is not always positive. Some degradation products can be used for other
commensals and opportunistic pathogens sharing similar nutritional preferences . Another example is
[103]
dietary deprivation, which is known to turn the microbiota’s metabolic activity toward utilizing host-
derived glycans like mucins. Mucin glycans are rich in fucose and sialic acid, which are also used as cross-
[104]
feeding metabolites . This degradation results in microbiome-mediated erosion of the mucosal barrier
and disruption of the barrier function . This disruption permits lethal colonization of Citrobacter
[104]
[104]
rodentium in mice, which under normal conditions does not cause a major infection . These findings
highlight the importance of diet in dysbiosis .
[104]
Exploitative competition: Some gut microbes, especially those that are taxonomically related, share similar
niche preferences and therefore engage in competition . Exploitative competition is a negative microbial
[29]
[105]
interaction defined by limited resources resulting in reduced microbial growth . Many gut microbes use
simple saccharides, which are highly demanded, resulting in competition. Competition for limited nutrients
results in pathogen starvation [72,106] . The intestinal lumen is an anaerobic environment, but oxygen diffusion
near the epithelium results in microaerophilic conditions . Pathogenic enterobacteria, such as Shigella
[27]
flexneri, face strong competition from commensal microbes for oxygen, which is critical for their
expansion [78,107] .

Gut commensals promote balanced immune responses and have a large arsenal of molecules that control
pathogenic growth . In contrast, pathogens such as S. typhimurium take advantage of a disrupted
[72]
microbiota to temporally colonize the host . Its infection causes mild intestinal inflammation that results
[108]
in macrophage activation and the production of radical oxygen species (ROS) and AMPs, disturbing the
[72]
stability of the microbiota and reducing the commensal population . Some ROS, such as tetrathionate and
thiosulfate, provide a competitive advantage to this pathogen by using them as alternative electron acceptors
in anaerobic respiration [109,110] . Therefore, inflammation is a mechanism by which some pathogens disrupt
colonization resistance. Salmonella-induced inflammation increases epithelial oxygenation by depleting
[111]
BPB . Antibiotic treatment also depletes commensal BPB, decreasing luminal butyrate concentrations .
[107]
The loss of BPB caused by antibiotics or dysbiosis explains the reduced butyrate absorption and increased
epithelial oxygenation. Higher intestinal oxygen concentrations favor the expansion of facultative anaerobes
in the gut, such as S. typhimurium .
[111]

Interference competition: It occurs when one or more microbes display antimicrobial activity against others.
Genes participating in this process are abundant in the genomes of gut microbes , and the gut microbiome
[24]
has been described as a warzone . Microcins are produced by Gram-negative bacteria, and lantibiotics or
[78]
bacteriocins are characteristic of Gram-positive bacteria. Microcins are found in 34% of sequenced
Escherichia coli strains, which might contribute to their establishment in the gut microbiota . Some
[112]
bacteriocins have practical applications in food safety , and some have inhibitory activity against
[113]
important pathogens such as C. difficile [114,115] .