Understanding How Commensal Obligate Anaerobic Bacteria Regulate Immune Functions in the Large Intestine

Abstract

The human gastrointestinal tract is colonised by trillions of commensal bacteria, most of which are obligate anaerobes residing in the large intestine. Appropriate bacterial colonisation is generally known to be critical for human health. In particular, the development and function of the immune system depends on microbial colonisation, and a regulated cross-talk between commensal bacteria, intestinal epithelial cells and immune cells is required to maintain mucosal immune homeostasis. This homeostasis is disturbed in various inflammatory disorders, such as inflammatory bowel diseases. Several in vitro and in vivo studies indicate a role for Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, Bacteroides fragilis, Akkermansia muciniphila and segmented filamentous bacteria in maintaining intestinal immune homeostasis. These obligate anaerobes are abundant in the healthy intestine but reduced in several inflammatory diseases, suggesting an association with protective effects on human health. However, knowledge of the mechanisms underlying the effects of obligate anaerobic intestinal bacteria remains limited, in part due to the difficulty of co-culturing obligate anaerobes together with oxygen-requiring human epithelial cells. By using novel dual-environment co-culture models, it will be possible to investigate the effects of the unstudied majority of intestinal microorganisms on the human epithelia. This knowledge will provide opportunities for improving human health and reducing the risk of inflammatory diseases.

Maternal exposure to a Western‐style diet causes differences in intestinal microbiota composition and gene expression of suckling mouse pups

“…The strong decrease in relative abundance of the Verrucomicrobiaceae member Akkermansia in the offspring of WS diet-fed dams is in line with previous studies in older mice after exposure to a high-fat diet [49]. Akkermansia, residing in the outer mucus layer of the colon, has been proposed as a marker for a healthy intestine due to its reduction in disease but high abundance in the healthy mucosa [50][51][52]. A protective or anti-inflammatory role in the intestinal mucosa has been proposed for this bacterium and reduced abundance of Akkermansia in humans has been previously shown in obese individuals and people with ulcerative colitis and Crohn's disease, underscoring the importance of this bacterium for gut health [52].…”

Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

“…Exchange of bacterial signals between the two strains caused B. thetaiotaomicron to generate more mucosal glycans in the intestine and E. rectale to decrease production of glycan-degrading enzymes and increase butyrate production, which strengthened the intestinal epithelium barrier [65]. This model and our data showing B. thetaiotaomicron and E. rectale as the most enriched taxa in the REF cohort suggest that reciprocal beneficial effects observed in a healthy bacterial ecosystem are hampered in the HBP cohort [66]. …”

Organoids, organs-on-chips and other systems, and microbiota

“…Additionally, in the absence of antibiotic media, some aerobic commensal microbes can be maintained [93]. Although this system holds great promise to study holistically the complex mechanisms that underpin healthy gut functions and disease in a 3D physiologically relevant environment, further work is required to maintain anaerobic microbes that are predominately found within the intestinal environment [94]. In addition to maintaining tissue slices in media, epithelial integrity, neural activity, ion/nutrient/drug transport [95][96][97], and the effect of microbiota and pathogenic bacteria on these processes [98][99][100][101] can be examined using analytical tools, such as the Ussing chamber.…”

“…The progression in generating primary epithelium and organoids from stem cells holds great promise for advancing these techniques to recreate the cellular makeup and environmental conditions prevalent in the human gut, especially in light of the available organoid monolayer Transwell culturing methods that utilises donor-specific tissue and enables co-culture with microbes [42,76,77] and which has the potential to be translated to organ-on-a-chip and HuMiX modelling systems. Secondly, most microfluidic devices have been sufficient only in culturing aerobic microbes, which does not reflect the anaerobic nature of the intestinal lumen [24,94]. The development of the state-of-the-art HuMiX system has provided a platform to culture aerobic-dependent epithelium in the presence of anaerobic microbes, but further refinement of this system is required to decipher the complex interactions between the holistic gut environment (stroma, immune system, diet, microbiome, and metabolome) and the roles they play in maintaining intestinal physiology and initiating and preventing intestinal diseases.…”