A recent Cell Death Discovery study discusses the role of Lactobacillus in treating inflammatory bowel disease (IBD).
Study: The role of Lactobacillus in inflammatory bowel disease: From actualities to prospects. Image Credit: ART-ur / Shutterstock.com
What is IBD?
IBD involves chronic inflammation of the intestine that causes diarrhea, abdominal pain, and bloody stools. IBD comprises Crohn’s disease (CD) and ulcerative colitis (UC), both of which prevail commonly across the world.
UC is associated with a series of superficial ulcers with intestinal crypt abscesses in the lamina propria. Comparatively, CD causes segmentally distributed deep ulcers with non-caseating granulomas in all layers of the intestinal wall.
Conventional treatment of IBD includes immunosuppressants, amino-salicylic acid, glucocorticoids, infliximab, and adalimumab. However, these treatments are associated with frequent relapse, which subsequently increases the disease burden in healthcare sectors. Thus, there remains an urgent need for an alternative treatment that will prevent and cure IBD.
Lactobacillus and IBD manifestations
The human gastrointestinal (GI) tract comprises various microorganisms, including bacteria, fungi, viruses, archaea, and parasites. These microbes are closely linked with the development and prognosis of intestinal diseases.
Some of these microorganisms, particularly bacteria like Firmicutes, Proteobacteria, Cyanobacteria, Bacteroidetes, Fusobacteria, Actinobacteria, and Verrucomicrobia, are associated with many physiological processes of the body.
The colitis mouse model has demonstrated the importance of Lactobacillus, a prominent member of Firmicutes, in IBD manifestation. Lactobacillus is an anaerobic, gram-positive bacteria that can break down glucose and other sugars into lactic acid.
A previous genomic study indicated that Lactobacillus accounts for 0.3% of the total bacterial population in the human colon and 6% of the human duodenum. This genus has many subspecies, including L. acidophilus, L. plantarum, L. casei, and L. salivarius.
Most Lactobacillus subspecies are beneficial to intestinal health, as demonstrated by their support in restoring the intestinal lining after excessive inflammation. Only a few Lactobacillus species, including Lactobacillus delbrueckii, can cause adverse effects, such as apoptosis and necrosis, in hosts.
Therapeutic effect of Lactobacillus in IBD
Patients with UC or CD exhibit higher neutrophil-to-lymphocyte ratio (NLR) in peripheral blood as compared to healthy individuals. The immune microenvironment of an inflamed colonic tissue is characterized by an abundance of activated dendritic cells (DCs), M1-like macrophages, monocytes, and plasmacytoid DCs. Therefore, reversing hyperactive pro-inflammatory cells could be a potential therapeutic target for IBD.
Several studies have indicated that many Lactobacillus species, such as L. reuteri and L. rhamnosus, can restore altered immune cell proportions. For example, L. reuteri increases the concentration of Tregs in mesenteric lymph nodes and prevents expansion of DCs and recruitment of neutrophils.
Mouse colitis models have demonstrated that L. rhamnosus reduces the Th17/Treg ratio through the Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway. L. rhamnosus can also induce mitochondrial pathway-dependent apoptosis of specific immune cells, particularly monocytes, without disturbing intestinal epithelial cells (IECs). These findings underscore the importance of Lactobacillus species for IBD treatment.
Both L. rhamnosus and L. salivarius protect mice from trinitrobenzene sulfonic acid (TNBS)-induced colitis. Mechanistically, both bacteria promoted DCs’ differentiation to a specific tolerogenic phenotype by neither inhibiting cytokines or chemokines production nor expressing co-stimulatory molecules to activate T-cells. These DCs exhibit anti-inflammatory properties by limiting the expression of pro-inflammatory mediators including interleukin-17 (IL-17) and IL-23 and overexpressing indoleamine 2, 3 dioxygenases (IDO).
Many Lactobacillus strains downregulate the production of pro-inflammatory mediators, such as IL-6, IL-1β, and tumor necrosis factor-α (TNF-α) in the inflamed tissues of colitis mice. The pattern recognition receptor (PRR) family was identified to play an important role in promoting the anti-inflammatory activity of various Lactobacillus strains.
L. rhamnosus secretes HM0539, a novel soluble protein that downregulates the expression of cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS). These factors inhibit the production of nitric oxide (NO) and prostaglandin E2 (PGE2), which are crucial inflammatory mediators in the GI tract.
Lactobacillus also increases the degradation of tissue-distributed inflammatory-related factors. Mice with colitis fed with L. casei exhibited improvement in their inflammation status.
Lactobacillus in IBD Treatment
Several probiotics, including various Lactobacillus strains, are designed for IBD patients. These fermented products provide anti-inflammatory effects and alleviate IBD manifestations.
In one experiment, single-strain Lactobacillus-fermented milk or cheese containing two Lactobacillus strains were fed to mice with colitis. All experimental groups exhibited modulation of intestinal and systemic inflammation, which successfully relieved severe symptoms.
Lactobacillus species protect against colonic oxidative stress and restore epithelial cell damage. Furthermore, as compared to a single strain, probiotics containing multiple strains of Lactobacillus, including L. gasseri, L. reuteri, and L. acidophilus, are associated with better therapeutic effectiveness in IBD patients.
Sybviotics, which are a combination of probiotics and prebiotics, along with vitamins and trace elements, offer positive results in IBD treatment. Lactobacillus interventions, particularly L. rhamnosus GG secreting p40, in combination with vitamin D, exhibit favorable results in IBD patients. In the future, more research is needed to evaluate the therapeutic efficacy of Lactobacillus in the treatment of IBD.
- Li, C., Peng, K., Xiao, S., et al. (2023) The role of Lactobacillus in inflammatory bowel disease: From actualities to prospects. Cell Death Discovery 9(1);1-12. doi:10.1038/s41420-023-01666-w