The gut microbiome: A line of defense against tuberculosis development

Abstract

The tuberculosis (TB) burden remains a significant global public health concern, especially in less developed countries. While pulmonary tuberculosis (PTB) is the most common form of the disease, extrapulmonary tuberculosis, particularly intestinal TB (ITB), which is mostly secondary to PTB, is also a significant issue. With the development of sequencing technologies, recent studies have investigated the potential role of the gut microbiome in TB development. In this review, we summarized studies investigating the gut microbiome in both PTB and ITB patients (secondary to PTB) compared with healthy controls. Both PTB and ITB patients show reduced gut microbiome diversity characterized by reduced Firmicutes and elevated opportunistic pathogens colonization; Bacteroides and Prevotella were reported with opposite alteration in PTB and ITB patients. The alteration reported in TB patients may lead to a disequilibrium in metabolites such as short-chain fatty acid (SCFA) production, which may recast the lung microbiome and immunity via the “gut-lung axis”. These findings may also shed light on the colonization of Mycobacterium tuberculosis in the gastrointestinal tract and the development of ITB in PTB patients. The findings highlight the crucial role of the gut microbiome in TB, particularly in ITB development, and suggest that probiotics and postbiotics might be useful supplements in shaping a balanced gut microbiome during TB treatment.

Study of the Relationship between Mucosal Immunity and Commensal Microbiota: A Bibliometric Analysis

“…Figure 6 A illustrates the top 25 citation bursts, with 15 studies cited highly for a sustained period of five years. The article Induction of intestinal Th17 cells by segmented filamentous bacteria [ 19 ], which has the highest co-citation frequency and the highest citation burst (Strength = 20.38), was published in the journal Cell in 2009. It reports that microbial symbiotic regulatory pathways may offer new opportunities for enhancing mucosal immunity and treating autoimmune diseases, providing strong evidence and a solid foundation for the study of mucosal immunity and commensal microbiota.…”

“…To be exact, the direct communicative actions of the body’s mucosa modulate the commensal microbiota and also exert systemic immunomodulatory effects through signaling pathways. It is widely known that the immune balance of the body could be modified with oral administration or intranasal inhalation of probiotics or prebiotics, or fecal transplantation of intestinal flora, for the treatment of various immune-related diseases throughout the body, such as inflammatory bowel disease [ 12 ], asthma [ 13 ], chronic obstructive pulmonary disease [ 14 , 15 ], influenza [ 16 ], COVID-19 [ 17 ], hepatitis B [ 18 ], tuberculosis [ 19 ], neuroinflammation-related depression, anxiety disorders [ 20 ], etc. Yet, the therapeutic use of prebiotics is limited because they are living organisms.…”

The Interplay between Mycobacterium tuberculosis and Human Microbiome

“…SCFAs are transported into host cells and bind to G-protein coupled receptors (GPCR) on epithelial and immune cells and produce anti-inflammatory cytokines [31,37,58,59]. Butyrate, which can act in the lungs by increasing the phagocytic function of dendritic cells, has been associated with anti-inflammatory properties during Mtb infections by causing a decrease in the proinflammatory cytokines and inhibiting host response to the infection [60][61][62][63]. Butyrate may also be converted to Phenylbutyrate (PBA), which has a synergistic effect with vitamin D to inhibit Mtb growth [64].…”

“…Butyrate may also be converted to Phenylbutyrate (PBA), which has a synergistic effect with vitamin D to inhibit Mtb growth [64]. This synergistic relationship upregulates LL-37, an antimicrobial peptide that increases the autophagy and intracellular killing of Mtb in host macrophages [62,65,66]. A study by Koh et al hypothesizes the important regulatory role of SCFAs in T cell differentiation and function due to the high expression of SCFA receptors in immune cells; however, more research is required to determine the specific mechanism and role of SCFAs in TB therapy [59].…”

Excess fermentation and lactic acidosis as detrimental functions of the gut microbes in treatment-naive TB patients

“…Crucially, the functional impact of the microbiota on host immunity, mediated through microbial metabolic output, is lacking. Thus, based on 16S rRNA sequencing, earlier studies reported gut dysbiosis and discussed the possible impact of the detected taxonomic changes on the host ( Hu et al., 2019 ; Shi et al., 2021 ; S. Wang et al., 2022 ; Yu et al., 2023 ). Such taxonomic descriptions are not enough to understand microbial function.…”