Gut microbiota: a crucial player in the combat against tuberculosis

Abstract

The mammalian gastrointestinal tract quickly becomes densely populated with foreign microorganisms shortly after birth, thereby establishing a lifelong presence of a microbial community. These commensal gut microbiota serve various functions, such as providing nutrients, processing ingested compounds, maintaining gut homeostasis, and shaping the intestinal structure in the host. Dysbiosis, which is characterized by an imbalance in the microbial community, is closely linked to numerous human ailments and has recently emerged as a key factor in health prognosis. Tuberculosis (TB), a highly contagious and potentially fatal disease, presents a pressing need for improved methods of prevention, diagnosis, and treatment strategies. Thus, we aim to explore the latest developments on how the host's immune defenses, inflammatory responses, metabolic pathways, and nutritional status collectively impact the host's susceptibility to or resilience against Mycobacterium tuberculosis infection. The review addresses how the fluctuations in the gut microbiota not only affect the equilibrium of these physiological processes but also indirectly influence the host's capacity to resist M. tuberculosis. This work highlights the central role of the gut microbiota in the host-microbe interactions and provides novel insights for the advancement of preventative and therapeutic approaches against tuberculosis.

Keywords: dysbiosis; gut microbiota; gut-lung axis; microecology; tuberculosis.

Figure 1

Interaction between microbiota, pathogens, and host immunity in health and TB-related inflammation. The gut microbiota plays a critical role in the construction of the mucosal barrier by interacting with immune cells, contributing to colonization resistance, and secreting metabolites that help maintain homeostasis. Close contact between luminal microbiota and epithelial cells triggers an immune response that can lead to inflammation and increase the likelihood of attack by opportunistic pathogens. Partial immune evasion by these pathogens can allow them to spread to organs such as the liver, lungs, and brain via the bloodstream or lymphatic circulation. Importantly, the commensal microbiota in both the gut and respiratory tract helps prevent lung infections by stimulating lung dendritic cells. The gut microbiota exhibits great potential as a reflector and modulator of TB. TLR, Toll-like receptors; Treg, regulatory T cell; MHCII, major compatibility complex II; ILC3, group 3 innate lymphoid cell; MAIT cell, mucosal-associated invariant T cell.

Figure 2

Relationships between gut microbiota and distinct TB. Gut microbiota vary across different stages of TB. Intestinal microbes become potential targets for indicating different states of TB and boosting immunity. However, high individual variation poses challenges in utilizing gut microbiota-based approaches for the diagnosis of TB. PTB, pulmonary tuberculosis; LTBI, latent tuberculosis infection; Pre-XDR-TB, pre-extensive drug-resistant tuberculosis; Tregs, regulatory T cells.

Figure 3

A healthy diet and normal gut microorganisms reduce TB susceptibility. A high-fermented food and a high-fiber diet can positively impact the gut microbiota and its metabolism, which can influence TB susceptibility through their effects on host genes. Gut microbiota changes anti-TB immunity by influencing host gene expression. SCFAs, short-chain fatty acids; DCs, dendric cells; TLRs, Toll-like receptors.

Figure 4

Several factors link the gut and the lungs. Alterations in gut microbiota have been observed in TB patients, highlighting the association between the gut microbiota and diseases. Several factors influence the interactions between gut microbiota and TB-infected organs, including genetic predispositions, dietary factors, material factors, antibiotic usage, and microbial transplantation. These factors influence the development and progression of TB.