Iron deficiency remains the most prevalent micronutrient deficiency globally, driven in large part by the limited bioavailability of non-heme iron and compounded by dietary inhibitors, inflammation-mediated hepcidin regulation, and challenges associated with conventional iron supplementation. Health effects of prolonged iron deficiency include heart irregularities, weakened immunity, and cognitive impairment. Growing evidence highlights the gut microbiome as a key modulator of nutrient absorption, with probiotics emerging as a promising adjunctive strategy. Among these, the Lactiplantibacillus plantarum strain Lp299v (LP299V®, proprietary strain of Probi®) has demonstrated consistent efficacy in enhancing non-heme iron bioavailability through multiple complementary mechanisms, including luminal acidification via organic acid production, stabilization and chelation of soluble iron complexes, facilitation of ferric-to-ferrous reduction, and potential mitigation of inhibitors such as phytates. Additional effects on host physiology, such as improved intestinal barrier function, increased short-chain fatty acid production, and attenuation of inflammation, further support its role in optimizing iron uptake. The present review gives an overview of how probiotic strains may modulate iron absorption, and more specifically focuses on describing effects obtained with the Lp299v strain. Ten peer-reviewed clinical studies have described the effects of Lp299v for increasing iron absorption. Human isotope studies show that Lp299v increases fractional iron absorption by approximately 20–50% across diverse dietary contexts, while randomized controlled trials and meta-analyses indicate meaningful improvements in iron status, particularly in populations with elevated requirements such as women of reproductive age, pregnant women, and athletes. From the mechanistic studies combined with clinical evidence, results suggest that Lp299v functions as a bioavailability enhancer rather than a substitute for iron intake. Given its versatility in delivery formats, favorable safety profile, and applicability across a range of dietary patterns and socioeconomic settings, Lp299v represents a microbiome-informed approach to addressing the persistent global burden of iron deficiency that has great potential for widespread adoption. This review aims to describe the gut microbiome as an important determinant of micronutrient bioavailability, and, more specifically, to summarize the data supporting Lp299v as a key modulator of iron absorption.

The disparity between increased lifespan and healthy aging, marked by prevalent “inflammaging”, highlights the global challenge in care of older persons. This study explored the anti-inflammatory effects of Lactiplantibacillus plantarum HEAL9 (LpHEAL9), alone or combined with berries, on older volunteers with chronic low-grade inflammation (LGI). It was a randomized, double-blind, placebo-controlled trial, with a total of 66 volunteers (> 70 years old), randomly assigned, and equally distributed, to placebo, LpHEAL9 or LpHEAL9 + Berries group. After a 2-week run-in period, participants underwent a 4-week dietary intervention. Intake of LpHEAL9 showed a trend towards reduction in serum CRP but without reaching statistical significance. However, LpHEAL9 significantly decreased fecal calprotectin levels compared to placebo. LpHEAL9+Berries did not show any effect on inflammation. Both probiotic groups showed a trend in improving cognitive function albeit not reaching statistical significance. Our findings suggest that the probiotic strain L. plantarum HEAL9 has a modest impact on LGI in a healthy older population (ClinicalTrials.gov ID: NCT02342496).

Background: The usage of probiotics has expanded beyond the areas of gut and immune health improvement. Several studies have shown the positive impact associated between probiotics and stress, cognition, and mood; a relationship referred to as the gut–brain axis. Method: The aim of this exploratory study was to evaluate the effect of the probiotic strain Lactiplantibacillus plantarum HEAL9 (LPHEAL9) on the gut–brain axis in subjects with moderate stress. One hundred and twenty-nine subjects aged 21–52 years completed the study, randomized to consume either LPHEAL9 (n = 65) or placebo (n = 64) for 12 weeks. Results: Perceived stress and awakening cortisol were significantly reduced over time in both groups. A significant improvement in four cognition tests after consumption of LPHEAL9 compared to placebo was observed (rapid information processing test, numeric working memory test, paired associated learning, and word recall, p < 0.05). There was a tendency for a significantly better improvement in the LPHEAL9 group for three mood subscales (Confusion–Bewilderment, Anger–Hostility, and Depression–Dejection) and for fewer subjects with poor sleep in the LPHEAL9 group compared to placebo (p < 0.10). Conclusions: Intake of LPHEAL9 significantly improved cognitive functions compared to the placebo, potentially by ameliorating aspects of mood and sleep.

Introduction Iron deficiency during pregnancy is a global health problem and is associated with adverse pregnancy outcomes. The aim of this randomized, double-blind, placebo-controlled study was to evaluate the effect of Lactiplantibacillus plantarum 299v (Lp299v, 10(10) colony forming units), 4.2 mg iron, 12 mg ascorbic acid and 30 mu g folic acid (Lp) on iron status in healthy, non-anemic, pregnant Swedish women. Material and methods A total of 326 women were randomized to receive Lp (n = 161) or placebo (n = 165) twice daily from gestational week 10-12 until end of pregnancy or until the potential start of iron therapy. The primary endpoint was serum ferritin at week 28. Results Intake of Lp attenuated the decrease in serum ferritin from baseline to week 28 (p = 0.003) and week 35 (p < 0.001) and resulted in reduced prevalence of iron deficiency (59% vs 78%, p = 0.017) and iron deficiency anemia (7.4% vs 21%, p = 0.023) at week 35. Intake of Lp also resulted in beneficial effects on the soluble transferrin receptor (p = 0.011) and total body iron (p < 0.001) at week 35. Gestational length and birthweight were comparable between groups. The proportion of women reporting adverse events during the study was comparable between groups. Conclusions Intake of Lp from early pregnancy was safe, attenuated the loss of iron stores and improved iron status in healthy pregnant women.

Background Different microorganisms from the environment will begin to colonise the infant during and immediately after the delivery. It could be advantageous to influence the microbiome early on by giving infants probiotic bacteria. The aim of the study was to investigate the tolerance of two probiotic lactobacilli in infants. The effect on the microbiota was also followed. Methods Thirty-six healthy infants, aged 4–83 days at the start of the study, were given a daily supplementation of probiotics ( Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus rhamnosus 271, 10 9 CFU (colony-forming units)) or placebo for 8 weeks. Adverse events, growth parameters, the faecal microbiome and intestinal performance were followed. Results No differences between the groups in growth parameters, adverse events and intestinal performance were observed. The faecal levels of L. plantarum , L. rhamnosus and lactobacilli increased after the intake of probiotics and were significantly higher compared with the placebo group after 4 and 8 weeks of intake. The faecal microbial diversity was similar in the two groups at the end of the study. Conclusions The intervention with the probiotic formulation was well tolerated and increased the level of lactobacilli in the intestine. The developed probiotic formulation will be further evaluated for clinical efficacy in infants. Impact New data for the development of the gut function and the microbiome in breastfed and/or formula-fed young infants over time and the effect of adding two probiotic strains are presented. Lactiplantibacillus plantarum is a species that seldom has been analysed in infants, but it could be detected in 25% of the subjects before administration (mean age 41 days). Lactiplantibacillus plantarum and L. rhamnosus establish well in the intestine of infants and are well tolerated. The microbiota was positively affected by the intake of probiotics.

Iron deficiency during pregnancy is a global health problem and is associated with adverse pregnancy outcomes. The aim of this randomized, double-blind, placebo-controlled study was to evaluate the effect of Lactiplantibacillus plantarum 299v (Lp299v, 10 10 colony forming units), 4.2 mg iron, 12 mg ascorbic acid and 30 µg folic acid (Lp) on iron status in healthy, non-anemic, pregnant Swedish women. A total of 326 women were randomized to receive Lp ( n  = 161) or placebo ( n  = 165) twice daily from gestational week 10–12 until end of pregnancy or until the potential start of iron therapy. The primary endpoint was serum ferritin at week 28. Intake of Lp attenuated the decrease in serum ferritin from baseline to week 28 ( p  = 0.003) and week 35 ( p  ˂ 0.001) and resulted in reduced prevalence of iron deficiency (59% vs 78%, p  = 0.017) and iron deficiency anemia (7.4% vs 21%, p  = 0.023) at week 35. Intake of Lp also resulted in beneficial effects on the soluble transferrin receptor ( p  = 0.011) and total body iron ( p  ˂ 0.001) at week 35. Gestational length and birthweight were comparable between groups. The proportion of women reporting adverse events during the study was comparable between groups. Intake of Lp from early pregnancy was safe, attenuated the loss of iron stores and improved iron status in healthy pregnant women.

Iron is an essential micronutrient for oxygen transport and mitochondrial metabolism and is critical for physical performance. Compromised iron stores are more commonly found among athletes, and females are especially at risk. Iron deficiency is generally treated using oral iron supplements. However, only a small proportion of ingested iron is absorbed, necessitating higher intakes, which may result in adverse side effects, reduced compliance, and inefficient repletion of iron stores. The probiotic strain Lactobacillus plantarum 299v (Lp299v) significantly increases intestinal iron absorption in meal studies. The present study was conducted to explore the effects of 20 mg of iron with or without Lp299v on iron status, mood state, and physical performance. Fifty-three healthy non-anemic female athletes with low iron stores (ferritin < 30 μg/L) were randomized, and 39 completed the study. Intake of Lp299v with iron for four weeks increased ferritin levels more than iron alone (13.6 vs. 8.2 µg/L), but the difference between the groups was not significant (p = 0.056). The mean reticulocyte hemoglobin content increased after intake of Lp299v compared to control (1.5 vs. 0.82 pg) after 12 weeks, but the difference between the group was not significant (p = 0.083). The Profile of Mood States (POMS) questionnaire showed increased vigor with Lp299v vs. iron alone after 12 weeks (3.5 vs. 0.1, p = 0.015). No conclusive effects on physical performance were observed. In conclusion, Lp299v, together with 20 mg of iron, could result in a more substantial and rapid improvement in iron status and improved vigor compared to 20 mg of iron alone. A larger clinical trial is needed to further explore these findings as well as the impact of Lp299v on physical performance.

The intestine and the brain are connected via the brain-gut axis and the intestinal microbiota influences the immune activation and signaling molecules that are involved in the stress response. The aim of the study was to investigate if intake of the probiotic strain Lactiplantibacillus plantarum HEAL9 (LPHEAL9) for four weeks could counteract elevated cortisol and inflammation levels in subjects with chronic stress that are exposed to an acute stress test (Trier Social Stress Test, TSST). Seventy participants were included, and 63 participants completed the study (LPHEAL9, n = 32; placebo, n = 31). Cardiovascular reactivity and cortisol levels were affected by the TSST, but no differences between the groups were observed. Intake of LPHEAL9 did, however, result in significantly decreased plasma levels of two inflammatory markers (soluble fractalkine and CD163) compared to placebo. In conclusion, intake of LPHEAL9 for four weeks may reduce inflammatory markers coupled to acute stress in chronically stressed individuals.

As diets change in response to ethical, environmental, and health concerns surrounding meat consumption, fermentation has potential to improve the taste and nutritional qualities of plant-based foods. In this study, cauliflower, white beans, and a 50:50 cauliflower-white bean mixture were fermented using different strains of Lactobacillus plantarum . In all treatments containing cauliflower, the pH was reduced to <4 after 18 h, while treatments containing only white beans had an average pH of 4.8 after 18 h. Following fermentation, the riboflavin, folate, and vitamin B 12 content of the cauliflower-white bean mixture was measured, and compared against that of an unfermented control. The riboflavin and folate content of the mixture increased significantly after fermentation. Relative to control samples, riboflavin increased by 76–113%, to 91.6 ± 0.6 μg/100 g fresh weight, and folate increased by 32–60%, to 58.8 ± 2.0 μg/100 g fresh weight. For one bacterial strain, L. plantarum 299, a significant 66% increase in vitamin B 12 was observed, although the final amount (0.048 ± 0.013 μg/100 g fresh weight) was only a small fraction of recommended daily intake. Measurements of amino acid composition in the mixture revealed small increases in alanine, glycine, histidine, isoleucine, leucine, and valine in the fermented sample compared to the unfermented control.

Iron absorption from a bread meal, added an encapsulated iron‐containing supplement, may be increased if the lactic acid bacteria L. plantarum (DSM 9843) is present. The aim of this study was to investigate the mechanism by which L. plantarum increases iron absorption. We have previously shown that lactic fermentation of mixed vegetables increased iron absorption in humans and voltammetric studies revealed that the level of ferric iron [Fe 3+ (H 2 O) 6 ] was increased in the fermented vegetables, compared to unfermented control. In this study, we detected a similar increase in ferric iron in the in vitro digested bread meal containing the supplement with L. plantarum . In a co‐culture of intestinal Caco‐2 cells and mucus‐producing goblet cells (HT29 MTX E12), we observed that the ferric reductase Dcytb increased in the presence of L. plantarum ‐containing iron supplements while the production of mucin (muc5a1c) decreased independent of L. plantarum . This suggests that the L. plantarum ‐effect on iron absorption is mediated through enhancing the Fe 3+ /Dcytb system. Support or Funding Information The work was financially supported by Probi AB This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

The virtual version of the Trier Social Stress Test (V-TSST) is an effective and standardized tool for social stress induction. This study aimed to examine gut permeability and physiological and inflammatory markers of reactivity to acute psychosocial stress. Forty young men were classified as high-stressed (HIGHS) or low-stressed (LOWS) according to the Shirom-Melamed Burnout Questionnaire. Cardiovascular reactivity and gut dysfunction were studied along with cortisol, zonulin and cytokines. Gut permeability was shown to be affected within one hour after the psychosocial stress induction, and shown to be dependent on age. Interleukin-6 increased with time, most pronounced at the end of the one-hour recovery after V-TSST, and was positively correlated to age. HIGHS experienced more abdominal dysfunction compared to LOWS. In conclusion, this study is the first to show fluctuations in gut permeability after psychosocial stress induction. This was partly associated with changes in inflammatory markers.

Several human interventions have indicated that Lactobacillus plantarum 299v (L. plantarum 299v) increases intestinal iron absorption. The aim of the present study was to investigate possible effects of L. plantarum 299v on the mechanisms of iron absorption on the cellular level. We have previously shown that lactic fermentation of vegetables increased iron absorption in humans. It was revealed that the level of ferric iron [Fe (H2O)(5)](2+) was increased after fermentation. Therefore, we used voltammetry to measure the oxidation state of iron in simulated gastrointestinal digested oat and mango drinks and capsule meals containing L. plantarum 299v. We also exposed human intestinal co-cultures of enterocytes and goblet cells (Caco-2/HT29 MTX) to the supplements in order to study the effect on proteins possibly involved (MUC5AC, DCYTB, DMT1, and ferritin). We detected an increase in ferric iron in the digested meals and drinks containing L. plantarum 299v. In the intestinal cell model, we observed that the ferric reductase DCYTB increased in the presence of L. plantarum 299v, while the production of mucin (MUC5AC) decreased independently of L. plantarum 299v. In conclusion, the data suggest that the effect of L. plantarum 299v on iron metabolism is mediated through driving the Fe3+/DCYTB axis.

Background The probiotic strain Lactobacillus plantarum 299v has earlier been shown to increase iron absorption when added to foods. However, it is not known if the same probiotic strain in a freeze-dried format included in a capsule increases the iron absorption. Objective The aim of this study was to test the hypotheses that non-heme iron absorption from a light meal is promoted by a simultaneous intake of freeze-dried Lactobacillus plantarum 299v (Lp299v, DSM 9843). Study design With a single blinded placebo controlled sequential design, iron absorption from a light breakfast meal administered with or without capsules containing 1010 cfu freeze-dried Lp299v was studied in healthy female volunteers of fertile age. The methodology used was a double isotope technique (59Fe and 55Fe). Two studies were performed using the same protocol. Results In study 1, the absorption of iron from a meal without Lp299v was found to be 17.4 ± 13.4%, and from an identical meal with Lp299v was found to be 22.4 ± 17.3% (mean ± SD). This difference was statistically significant (p = 0.040, n = 14). In study 2, the absorption of iron from a meal without Lp299v was found to be 20.9 ± 13.1%, and from an identical meal with Lp299v found to be 24.5 ± 12.0% (mean ± SD, n = 28), which again was statistically significant (p = 0.003). Conclusion Freeze-dried Lp299v enhances the absorption of iron when administered together with a meal with a high iron bioavailability. Trial registration ClinicalTrials.gov Identifier: NCT02131870

OBJECTIVES:To determine if Lactobacillus plantarum DSM9843 (LP299V) reduces the frequency of antibiotic-associated loose/watery stools and gastrointestinal symptoms, and can be administered safely to children who are prescribed antibiotics. STUDY DESIGN:We performed a prospective, double-blind, randomized, placebo-controlled, multicenter, parallel-group study in children receiving outpatient antibiotic therapy in primary healthcare settings. The children were given LP299V/placebo during the antibiotic therapy and for 1 week after the end of treatment. The primary outcome measure was the incidence of at least 1 loose/watery stool (type 6 or 7 according to the Bristol Stool Form Scale). Gastrointestinal symptoms (abdominal pain, abdominal distention, vomiting, and flatulence) were followed up until 1 week after the last intake of the study product. RESULTS:A total of 438 children (male: 235, female: 203) aged 1-11 years (mean ± SD: 5.2 ± 2.7) were randomized to receive LP299V (N = 218) or placebo (N = 220). The incidence of loose/watery stools in the 2 study groups (LP299V and placebo) was similar, 39% vs 44.5% respectively (P = .26) as was the mean number of loose/watery stools (3.9 ± 3.5 vs 4.7 ± 6.3; P = .9). Antibiotic-associated diarrhea (defined as ≥3 loose/watery stools/24 hours starting from 2 hours after initiation of antibiotic treatment until the end of the study) occurred in 2.8% of the subjects receiving LP299V compared with 4.1% in the placebo arm (P = .4). The number of children with abdominal symptoms did not differ between the groups. CONCLUSIONS:No beneficial effect of LP299V compared with placebo was observed for the incidence of loose/watery stools, mean number of loose/watery stools, or the incidence of abdominal symptoms. LP299V had a satisfactory safety profile. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01940913.

BACKGROUND:A healthy Nordic diet is associated with improvements in cardiometabolic risk factors, but the effect on lipidomic profile is not known.OBJECTIVE:The aim was to investigate how a healthy Nordic diet affects the fasting plasma lipidomic profile in subjects with metabolic syndrome.METHODS:Men and women (n = 200) with features of metabolic syndrome [mean age: 55 y; body mass index (in kg/m2): 31.6] were randomly assigned to either a healthy Nordic (n = 104) or a control (n = 96) diet for 18 or 24 wk at 6 centers. Of the participants, 156 completed the study with plasma lipidomic measurements. The healthy Nordic diet consisted of whole grains, fruits, vegetables, berries, vegetable oils and margarines, fish, low-fat milk products, and low-fat meat. An average Nordic diet served as the control diet and included low-fiber cereal products, dairy fat-based spreads, regular-fat milk products, and a limited amount of fruits, vegetables, and berries. Lipidomic profiles were measured at baseline, week 12, and the end of the intervention (18 or 24 wk) by using ultraperformance liquid chromatography mass spectrometry. The effects of the diets on the lipid variables were analyzed with linear mixed-effects models. Data from centers with 18- or 24-wk duration were also analyzed separately.RESULTS:Changes in 21 plasma lipids differed significantly between the groups at week 12 (false discovery rate P < 0.05), including increases in plasmalogens and decreases in ceramides in the healthy Nordic diet group compared with the control group. At the end of the study, changes in lipidomic profiles did not differ between the groups. However, when the intervention lasted 24 wk, changes in 8 plasma lipids that had been identified at 12 wk, including plasmalogens, were sustained. There were no differences in changes in plasma lipids between groups with an intervention of 18 wk. By the dietary biomarker score, adherence to diet did not explain the difference in the results related to the duration of the study.CONCLUSIONS:A healthy Nordic diet transiently modified the plasma lipidomic profile, specifically by increasing the concentrations of antioxidative plasmalogens and decreasing insulin resistance-inducing ceramides. This trial was registered at clinicaltrials.gov as NCT00992641.