L‐lactate promotes intestinal epithelial cell migration to inhibit colitis

Yu, Yu; Yang, Wenjing; Bilotta, Anthony J.; Zhao, Xiaojing; Cong, Yingzi; Li, Yanqing

doi:10.1096/fj.202100095r

Cited by 10 publications

(7 citation statements)

References 79 publications

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“…In humans, strains of lactic acid bacteria (LAB) exert health-promoting functions such as immunomodulatory improvement of intestinal integrity, resistance to pathogens, prevention of lactose intolerance, anticancer effects, reduction of depression and anxiety symptoms, anti-obesity and anti-diabetic activities, and decrease serum cholesterol levels (55). L-lactate in drinking water can suppress colitis induced by dextran sulfate sodium in mice, promoting epithelial cell migration and repair through the augment of mitochondrial ATP production (56). On the other hand, microbiota-derived lactate, DL-lactate, regulates gut epithelium development, whereas LAB lacking LDH fails to induce intestinal stem-cell regeneration (57).…”

Section: Sources and Metabolismmentioning

confidence: 99%

Role of Lactate in Inflammatory Processes: Friend or Foe

et al. 2022

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During an inflammatory process, shift in the cellular metabolism associated with an increase in extracellular acidification are well-known features. This pH drop in the inflamed tissue is largely attributed to the presence of lactate by an increase in glycolysis. In recent years, evidence has accumulated describing the role of lactate in inflammatory processes; however, there are differences as to whether lactate can currently be considered a pro- or anti-inflammatory mediator. Herein, we review these recent advances on the pleiotropic effects of lactate on the inflammatory process. Taken together, the evidence suggests that lactate could exert differential effects depending on the metabolic status, cell type in which the effects of lactate are studied, and the pathological process analyzed. Additionally, various targets, including post-translational modifications, G-protein coupled receptor and transcription factor activation such as NF-κB and HIF-1, allow lactate to modulate signaling pathways that control the expression of cytokines, chemokines, adhesion molecules, and several enzymes associated with immune response and metabolism. Altogether, this would explain its varied effects on inflammatory processes beyond its well-known role as a waste product of metabolism.

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Section: Sources and Metabolismmentioning

confidence: 99%

Role of Lactate in Inflammatory Processes: Friend or Foe

et al. 2022

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“…Another very common microbial metabolite, lactate, has been found to exhibit healing properties on the intestinal mucosa both in vitro and in vivo. Specifically, L-lactate treatment was found to promote the migration rate of murine intestinal epithelial cells by enhancing their mitochondrial ATP production and to ameliorate colitis in mice, by inducing the expression of Cdc42 and Pak1, two factors associated with intestinal epithelial cell migration [134]. These results suggest that the communication between the host and the microbiota does not depend just on cellular interactions, but reach deeper, as microbiota's secreted factors actively influence the host's cellular processes.…”

Section: Metabolite Effect Referencementioning

confidence: 89%

Probiotics in Intestinal Mucosal Healing: A New Therapy or an Old Friend?

Filidou¹,

Kolios²

2021

Pharmaceuticals

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Inflammatory bowel disease (IBD), Crohn’s disease, and ulcerative colitis are characterized by chronic and relapsing inflammation, while their pathogenesis remains mostly unelucidated. Gut commensal microbiota seem to be one of the various implicated factors, as several studies have shown a significant decrease in the microbiome diversity of patients with IBD. Although the question of whether microbiota dysbiosis is a causal factor or the result of chronic inflammation remains unanswered, one fact is clear; active inflammation in IBD results in the disruption of the mucus layer structure, barrier function, and also, colonization sites. Recently, many studies on IBD have been focusing on the interplay between mucosal and luminal microbiota, underlining their possible beneficial effect on mucosal healing. Regarding this notion, it has now been shown that specific probiotic strains, when administrated, lead to significantly decreased inflammation, amelioration of colitis, and improved mucosal healing. Probiotics are live microorganisms exerting beneficial effects on the host’s health when administered in adequate quantity. The aim of this review was to present and discuss the current findings on the role of gut microbiota and their metabolites in intestinal wound healing and the effects of probiotics on intestinal mucosal wound closure.

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“…During repair, epithelial cells undergo morphologic changes in shape, modify cell-cell contacts, and migrate collectively to reseal the barrier ( 1 ). Given the importance of polarized epithelial cell migration to achieve wound repair, we analyzed the influence of LTB 4 on directional migration of epithelial cells using DiPer software ( 20 ) ( 22 , 23 ). These analyses suggest that LTB 4 signaling regulates collective IEC migration through enhanced directional persistence and speed of cell movement.…”

Section: Discussionmentioning

confidence: 99%

Intestinal epithelial BLT1 promotes mucosal repair

Hayashi¹,

Muraleedharan²,

Oku³

et al. 2022

JCI Insight

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Acute and chronic intestinal inflammation is associated with epithelial damage, resulting in mucosal wounds in the forms of erosions and ulcers in the intestinal tract. Intestinal epithelial cells (IECs) and immune cells in the wound milieu secrete cytokines and lipid mediators to influence repair. Leukotriene B4 (LTB4), a lipid chemokine, binds to its receptor BLT1 and promotes migration of immune cells to sites of active inflammation, however a role for intestinal epithelial BLT1 during mucosal wound repair is not known. Here we report that BLT1 is expressed in IECs both in vitro and in vivo, where it functions as a receptor not only for LTB4 but also for another ligand Resolvin E1. Intestinal epithelial BLT1 expression is increased when epithelial cells are exposed to an inflammatory microenvironment. Using human and murine primary colonic epithelial cells, we reveal that LTB4-BLT1 pathway promotes epithelial migration and proliferation leading to accelerated epithelial wound repair. Furthermore, in vivo intestinal wound repair experiments in BLT1-deficient mice and bone marrow chimeras demonstrate an important contribution of epithelial BLT1 during colonic mucosal wound repair. Taken together, our findings show a novel pro-repair in IEC mechanism mediated by BLT1 signaling.

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L‐lactate promotes intestinal epithelial cell migration to inhibit colitis

Cited by 10 publications

References 79 publications

Role of Lactate in Inflammatory Processes: Friend or Foe

Role of Lactate in Inflammatory Processes: Friend or Foe

Probiotics in Intestinal Mucosal Healing: A New Therapy or an Old Friend?

Intestinal epithelial BLT1 promotes mucosal repair

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