LACTOBACILLUS FERMENT LYSATE

The gut microbial ecosystem, which is a collection of the host-microbiota interactions and the inter-species interplay among bacteria-dominated microbiota, has become a research hotspot due to its contribution to host health in recent years. Lactobacillus, which has worldwide usage in fermented dairy products, has aroused increasing attention and becomes one of the commonly used probiotics given its promising applications in intestinal health and disease, though it occupies a relatively small proportion of the intestinal microbiota. In the review, we first update the current understanding of determinants of Lactobacillus abundance in the intestinal tract. We then review evidence from animal models to human trials that provided insights into Lactobacillus's applications in common intestinal disorders including the Helicobacter pylori infection, colorectal cancer, diarrhea, inflammatory bowel disease, and irritable bowel syndrome. Mechanisms underlying the probiotic role of Lactobacillus are finally discussed in five aspects: microbial interactions, the improvement of intestinal barrier function, the immunoregulation, the anticancer activity, and the metabolic regulation. This review aims to yield a profound understanding of how Lactobacillus will contribute to disease prevention and individualized therapies in future clinical practice, and to inspire novel microbial strategies utilizing both probiotics and their products in the fields of biology and medicine.

Digestive system diseases have evolved into a growing global burden without sufficient therapeutic measures. Lactobacillus reuteri ( L. reuteri ) is considered as a new potential economical therapy for its probiotic effects in the gastrointestinal system. We have provided an overview of the researches supporting various L. reuteri strains' application in treating common digestive system diseases, including infantile colic, diarrhea, constipation, functional abdominal pain, Helicobacter pylori infection, inflammatory bowel disease, diverticulitis, colorectal cancer and liver diseases. The summarized literature in this review was derived from databases including PubMed, Web of Science, and Google Scholar. The therapeutic effects of L. reuteri in digestive system diseases may depend on various direct and indirect mechanisms, including metabolite production as well as modulation of the intestinal microbiome, preservation of the gut barrier function, and regulation of the host immune system. These actions are largely strain-specific and depend on the activation or inhibition of various certain signal pathways. It is well evidenced that L. reuteri can be effective both as a prophylactic measure and as a preferred therapy for infantile colic, and it can also be recommended as an adjuvant strategy to diarrhea, constipation, Helicobacter pylori infection in therapeutic settings. While preclinical studies have shown the probiotic potential of L. reuteri in the management of functional abdominal pain, inflammatory bowel disease, diverticulitis, colorectal cancer and liver diseases, its application in these disease settings still needs further study. This review focuses on the probiotic effects of L. reuteri on gut homeostasis via certain signaling pathways, and emphasizes the importance of these probiotics as a prospective treatment against several digestive system diseases.

Lactobacillus iners , first described in 1999, is a prevalent bacterial species of the vaginal microbiome. As L. iners does not easily grow on de Man-Rogosa-Sharpe agar, but can grow anaerobically on blood agar, it has been initially overlooked by traditional culture methods. It was not until the wide application of molecular biology techniques that the function of L. iners in the vaginal microbiome was carefully explored. L. iners has the smallest genome among known Lactobacilli and it has many probiotic characteristics, but is partly different from other major vaginal Lactobacillus species, such as L. crispatus , in contributing to the maintenance of a healthy vaginal microbiome. It is not only commonly present in the healthy vagina but quite often recovered in high numbers in bacterial vaginosis (BV). Increasing evidence suggests that L. iners is a transitional species that colonizes after the vaginal environment is disturbed and offers overall less protection against vaginal dysbiosis and, subsequently, leads to BV, sexually transmitted infections, and adverse pregnancy outcomes. Accordingly, under certain conditions, L. iners is a genuine vaginal symbiont, but it also seems to be an opportunistic pathogen. Further studies are necessary to identify the exact role of this intriguing species in vaginal health and diseases.

Preterm birth, C-sections, antibiotics, and limited breastfeeding contribute to the increase in noncommunicable diseases. Our objective was to perform a descriptive review of probiotic use in pediatrics, focused on Lactobacillus rhamnosus GG. Certain probiotics have demonstrated to be effective in acute diarrhea and antibiotic-associated diarrhea. L. rhamnosus GG and Saccharomyces boulardii may shorten their duration and symptoms. L. reuteri DSM 17938 and L. rhamnosus GG were effective to manage infant colic. The use of this strain in infant formulas for cow's milk protein allergy may promote an earlier tolerance acquisition. In relation to the prevention of atopic dermatitis, the administration of L. rhamnosus GG during pregnancy reduced its development in the infant. The use of probiotics as adjuvants is a possibility to consider in current pediatric practice. El parto prematuro, las cesáreas, los antibióticos y la lactancia materna limitada contribuyen al aumento de enfermedades crónicas no transmisibles. El objetivo fue realizar una revisión descriptiva del uso de probióticos en pediatría, con foco en la cepa Lactobacillus rhamnosus GG. Ciertos probióticos han demostrado ser eficaces en la diarrea aguda y en la diarrea asociada a antibióticos. L. rhamnosus GG y Saccharomyces boulardii pueden acortar la duración y los síntomas. L. reuteri DSM 17938 y L. rhamnosus GG fueron efectivos para el abordaje del cólico del lactante. El uso de esta cepa en fórmulas infantiles para alergia a las proteínas de leche de vaca promovería la adquisición más temprana de tolerancia. En la prevención de dermatitis atópica, la administración de L. rhamnosus GG durante el embarazo redujo su manifestación en el bebé. El empleo de probióticos como coadyuvantes es una posibilidad para considerar en la práctica pediátrica actual.

The effects of probiotic interventions on colonization with resistant bacteria and early microbiome development in preterm infants remain to be clarified. To examine the efficacy of Bifidobacterium longum subsp infantis, Bifidobacterium animalis subsp lactis (BB-12), and Lactobacillus acidophilus (La-5) probiotics to prevent colonization with multidrug-resistant organisms or highly epidemic bacteria (MDRO+) and to shape the microbiome of preterm infants toward the eubiotic state of healthy full-term infants. The multicenter, double-blinded, placebo-controlled, group sequential, phase 3 Priming Immunity at the Beginning of Life (PRIMAL) randomized clinical trial, conducted from April 2018 to June 2020, included infants with gestational age of 28 to 32 weeks at 18 German neonatal units. Data analyses were conducted from March 2020 to August 2023. A total of 28 days of multistrain probiotics diluted in human milk/formula starting within the first 72 hours of life. Colonization with MDRO+ at day 30 of life (primary end point), late-onset sepsis and severe gastrointestinal complication (safety end points), and gut dysbiosis, ie, deviations from the microbiome of healthy, term infants (eubiosis score) based on 16-subunit ribosomal RNA and metagenomic sequencing. Among the 643 infants randomized until the stop of recruitment based on interim results, 618 (median [IQR] gestational age, 31.0 [29.7-32.1] weeks; 333 male [53.9%]; mean [SD] birth weight, 1502 [369] g) had follow-up at day 30. The interim analysis with all available data from 219 infants revealed MDRO+ colonization in 43 of 115 infants (37.4%) in the probiotics group and in 39 of 104 infants (37.5%) in the control group (adjusted risk ratio, 0.99; 95% CI, 0.54-1.81; P = .97). Safety outcomes were similar in both groups, ie, late-onset sepsis (probiotics group: 8 of 316 infants [2.5%]; control group: 12 of 322 infants [3.7%]) and severe gastrointestinal complications (probiotics group: 6 of 316 infants [1.9%]; control group: 7 of 322 infants [2.2%]). The probiotics group had higher eubiosis scores than the control group at the genus level (254 vs 258 infants; median scores, 0.47 vs 0.41; odds ratio [OR], 1.07; 95% CI, 1.02-1.13) and species level (96 vs 83 infants; median scores, 0.87 vs 0.59; OR, 1.28; 95% CI, 1.19-1.38). Environmental uptake of the B infantis probiotic strain in the control group was common (41 of 84 [49%]), which was highly variable across sites and particularly occurred in infants with a sibling who was treated with probiotics. Multistrain probiotics did not reduce the incidence of MDRO+ colonization at day 30 of life in preterm infants but modulated their microbiome toward eubiosis. German Clinical Trials Register: DRKS00013197.

Bacterial vaginosis (BV) is a common infection of the lower genital tract with a vaginal microbiome dysbiosis caused by decreasing of lactobacilli. Previous studies suggested that supplementation with live Lactobacillus may benefit the recovery of BV, however, the outcomes vary in people from different regions. Herein, we aim to evaluate the effectiveness of oral Chinese-origin Lactobacillus with adjuvant metronidazole (MET) on treating Chinese BV patients. In total, 67 Chinese women with BV were enrolled in this parallel controlled trial and randomly assigned to two study groups: a control group treated with MET vaginal suppositories for 7 days and a probiotic group treated with oral Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 as an adjuvant to MET for 30 days. By comparing the participants with Nugent Scores ≥ 7 and < 7 on days 14, 30, and 90, we found that oral administration of probiotics did not improve BV cure rates (72.73% and 84.00% at day 14, 57.14% and 60.00% at day 30, 32.14% and 48.39% at day 90 for probiotic and control group respectively). However, the probiotics were effective in restoring vaginal health after cure by showing higher proportion of participants with Nugent Scores < 4 in the probiotic group compared to the control group (87.50% and 71.43% on day 14, 93.75% and 88.89% on day 30, and 77.78% and 66.67% on day 90). The relative abundance of the probiotic strains was significantly increased in the intestinal microbiome of the probiotic group compared to the control group at day 14, but no significance was detected after 30 and 90 days. Also, the probiotics were not detected in vaginal microbiome, suggesting that L. gasseri TM13 and L. crispatus LG55 mainly acted through the intestine. A higher abundance of Prevotella timonensis at baseline was significantly associated with long-term cure failure of BV and greatly contributed to the enrichment of the lipid IVA synthesis pathway, which could aggravate inflammation response. To sum up, L. gasseri TM13 and L. crispatus LG55 can restore the vaginal health of patients recovering from BV, and individualized intervention mode should be developed to restore the vaginal health of patients recovering from BV. https://classic.clinicaltrials.gov/ct2/show/, identifier NCT04771728.