Lactulose — a sweet syrup that feeds good bacteria?

Aim of the study: Although medium and high doses of lactulose are used routinely for the treatment of constipation and hepatic encephalopathy, respectively, a wealth of evidence demonstrates that, at low doses, lactulose can also be used as a prebiotic to stimulate the growth of health-promoting bacteria in the gastrointestinal tract.

Results: SCFAs produced upon microbial fermentation of lactulose, the most abundant of which is acetate, are likely to contribute to immune regulation, which is important not only within the gut itself, but also systemically and for bone health. Low-dose lactulose has also been shown to enhance the absorption of minerals such as calcium and magnesium from the gut, an effect which may have important implications for bone health. This review provides an overview of the preclinical and clinical evidence published to date showing that low-dose lactulose stimulates the growth of health-promoting gut bacteria, inhibits the growth of pathogenic bacteria, increases the production of beneficial metabolites, improves mineral absorption, and has good overall tolerability. Implications of these data for the use of lactulose as a prebiotic are also discussed.

Aim of the study: Intestinal dysfunction is one of the common complications in the early stage of acute pancreatitis (AP), which often associates with bad outcome. Lactulose, as a prebiotic, has been widely used to improve gut health, yet its effect on AP is unclear.

Results: The intestinal dysfunction was prominently improved after 7 days of treatment with either lactulose or rhubarb. The serum levels of cytokines and gut permeability index were decreased after treatment, with stronger down-regulated degree in lactulose group than rhubarb. The potential beneficial genus Bifidobacterium was enriched in lactulose group, while pathogenic bacteria including Escherichia-Shigella and Neisseria were abundant in rhubarb group. Of note, the level of SCFAs was remarkably increased after treatment, with higher amount in lactulose group than rhubarb group. Lactulose could not only restore intestinal function but also regulate gut microbiota and promote the production of SCFAs.

Aim of the study: Gut microbiota have strong connections with health. Lactulose has been shown to regulate gut microbiota and benefit host health.

Results: In this study, the effect of short-term (3 week) intervention of lactulose on gut microbiota was investigated. Gut microbiota were detected from mouse feces by 16S rRNA high-throughput sequencing, and short chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry (GC-MS). Lactulose intervention enhanced the α-diversity of the gut microbiota; increased the abundance of hydrogen-producing bacteria Prevotellaceae and Rikenellaceae, probiotics Bifidobacteriaceae and Lactobacillaceae, and mucin-degrading bacteria Akkermansia and Helicobacter; decreased the abundance of harmful bacteria Desulfovibrionaceae and branched-chain SCFAs (BCFAs). These results suggest that lactulose intervention effectively increased the diversity and improved the structure of the intestinal microbiota, which may be beneficial for host health.

Aim of the study: Lactulose is a common laxative and has been widely applied to clinical treatment for constipation. This study aimed to explore the improving effect of lactulose on constipation through the mediation of gut microbiota and intestinal metabolites.

Results: The treatment of constipated mice with lactulose accelerated intestinal motility, suppressed inflammatory responses, protected gut barrier, and improved metabolisms of water and salt in the intestinal tract. These therapeutic effects were attributed to the reversed gut microbiota dysfunction, which conferred the benefit to the production of intestinal metabolites including bile acids, short-chain fatty acids, and tryptophan catabolites. Further, the depletion of intestinal flora from loperamide- or (loperamide + lactulose)-treated mice confirmed the significance of gut microbiota in the mediation of constipation. In summary, this study leads us to propose that lactulose may improve constipation through a prebiotic effect on gut microbiota and intestinal metabolites.

Aim of the study: Recently, we reported that lactulose, a synthetic disaccharide used to treat chronic constipation, improved the gut-renal axis in mice with adenine-induced CKD. However, the underlying mechanism remains unclear. Akkermansia muciniphila (AKK), a next-generation probiotic, mitigates multiorgan dysfunction, including kidney impairment, by modulating intestinal health.

Results: Lactulose administration significantly ameliorated renal impairment in CKD mice and improved intestinal barrier integrity by increasing intestinal mucosal thickness. In addition, lactulose modulated CKD-induced gut dysbiosis, thereby altering microbiota diversity and composition with a notable increase in AKK abundance. This was further supported by in vitro findings that demonstrated a significant increase in AKK proliferation upon lactulose treatment. Similar to lactulose, oral administration of AKK (both live and pasteurized forms) for 3 weeks attenuated renal damage in CKD mice. Moreover, both forms of AKK significantly improved intestinal barrier function by enhancing mucosal integrity. Our findings suggest that lactulose functions as an in vivo AKK inducer, exerting renoprotective effects by improving intestinal barrier function in CKD. These results highlight the potential of lactulose as a prebiotic therapeutic agent for CKD management.

Aim of the study: Lactulose is a disaccharide used in clinical practice since 1957 and has since been tested in the treatment of many human disorders, including chronic constipation, hepatic encephalopathy, and chronic kidney disease. Its mode of action is based on the lactulose fermentation by intestinal microbiota.

Results: Its mode of action is based on the lactulose fermentation by intestinal microbiota. Based on in silico, in vitro and in vivo studies we comprehensively review here the impact of lactulose on human gut/fecal and vaginal microbiota composition and both fecal and blood metabolomes. However, both in vitro and in vivo studies summarized in this review have revealed that the effects of lactulose on human microbiota composition are both patient- and dose-dependent. This highlights the need of heterogeneity indication in clinical trials.

Aim of the study: To evaluate the efficacy of lactulose in the treatment of elderly constipation patients with chronic renal insufficiency and its influence on renal function.

Results: Both lactulose and PEG could improve the symptoms of constipation, and no significant difference was observed (p = 0.995). After lactulose treatment for 4 weeks, the serum levels of creatinine, uric acid, and IL-6 reduced significantly (p < 0.050), but they remained unchanged after treatment with PEG for 4 weeks (p > 0.050). At the genus level, the abundance of Anaerofustis stercorihominis (related to the production of short-chain fatty acids) increased markedly (p < 0.050), and the abundance of Halomonadaceae (related to the production of uremic toxins), Eikenella (one of the opportunistic pathogenic bacteria), and Sphingomonas (related to nitrogen metabolism) reduced significantly after lactulose treatment. Lactulose can improve renal function, mild inflammation, and gut microbiota in these patients. We speculate that the improvement of renal function after lactulose treatment may be related to the improvement of gut microbiota and systemic mild inflammation.