Wound healing is a multi-factorial response to tissue injury, aiming to restore tissue continuity. Numerous recent experimental and clinical studies clearly indicate that probiotics are applied topically to promote the wound-healing process. However, the precise mechanism by which they contribute to healing is not yet clear. Each strain appears to exert a distinctive, even multi-factorial action on different phases of the healing process. Given that a multi-probiotic formula exerts better results than a single strain, the pharmaceutical industry has embarked on a race for the production of a formulation containing a combination of probiotics capable of playing a role in all the phases of the healing process. Hence, the object of this review is to describe what is known to date of the distinctive mechanisms of each of the most studied probiotic strains in order to further facilitate research toward the development of combinations of strains and doses, covering the whole spectrum of healing. Eleven probiotic species have been analyzed, the only criterion of inclusion being a minimum of two published research articles.

/pdf/looking-for-the-ideal-probiotic-healing-regime-ccqwil5i.pdf

Looking for the Ideal Probiotic Healing Regime

Preterm infants are at risk of hypoxia and hyperoxia because of the immaturity of their respiratory and antioxidant systems, linked to increased morbidity and mortality. This study aimed to evaluate the efficacy of a single administration of the SLAB51 probiotic formula in improving oxygenation in respiratory distress syndrome (RDS)-affected premature babies, thus reducing their need for oxygen administration. Additionally, the capability of SLAB51 in activating the factor-erythroid 2-related factor (Nrf2) responsible for antioxidant responses was evaluated in vitro. In two groups of oxygen-treated preterm infants with similar SaO2 values, SLAB51 or a placebo was given. After two hours, the SLAB51-treated group showed a significant increase in SaO2 levels and the SaO2/FiO2 ratio, while the control group showed no changes. Significantly increased Nrf2 activation was observed in intestinal epithelial cells (IECs) exposed to SLAB51 lysates. In preterm infants, we confirmed the previously observed SLAB51's "oxygen-sparing effect", permitting an improvement in SaO2 levels. We also provided evidence of SLAB51's potential to enhance antioxidant responses, thus counteracting the detrimental effects of hyperoxia. Although further studies are needed to support our data, SLAB51 represents a promising approach to managing preterm infants requiring oxygen supplementation. 

SLAB51 Multi-Strain Probiotic Formula Increases Oxygenation in Oxygen-Treated Preterm Infants

Wound infections caused by opportunistic bacteria promote persistent infection and represent the main cause of delayed healing. Probiotics are acknowledged for their beneficial effects on the human body and could be utilized in the management of various diseases. They also possess the capacity to accelerate wound healing, due to their remarkable anti-pathogenic, antibiofilm, and immunomodulatory effects. Oral and topical probiotic formulations have shown promising openings in the field of dermatology, and there are various in vitro and in vivo models focusing on their healing mechanisms. Wound dressings embedded with prebiotics and probiotics are now prime candidates for designing wound healing therapeutic approaches to combat infections and to promote the healing process. The aim of this review is to conduct an extensive scientific literature review regarding the efficacy of oral and topical probiotics in wound management, as well as the potential of wound dressing embedding pre- and probiotics in stimulating the wound healing process.

Probiotics in Wound Healing

Probiotics and liver fibrosis: An evidence-based review of the latest research

Alzheimer’s disease (AD) is one of the major causes of dementia and its incidence represents approximately 60–70% of all dementia cases worldwide. Many theories have been proposed to describe the pathological events in AD, including deterioration in cognitive function, accumulation of β-amyloid, and tau protein hyperphosphorylation. Infection as well as various cellular molecules, such as apolipoprotein, micro-RNA, calcium, ghrelin receptor, and probiotics, are associated with the disruption of β-amyloid and tau protein hemostasis. This review gives an overview on the integrative cellular and signaling molecules that could play a complementary role in the dysregulation of β-amyloid and tau proteins. 

Overview of the Molecular Modalities and Signaling Pathways Intersecting with β-Amyloid and Tau Protein in Alzheimer’s Disease

Abstract Background Abnormal and deregulated skin wound healing associated with prolonged inflammation may result in dermal fibrosis. Since the current therapeutic strategies revealed unsatisfactory, the investigation of alternative approaches such as those based on the use of specific probiotic strains could provide promising therapeutic options. In this study, we aimed to evaluate whether the lysate from S. thermophilus could antagonize the fibrogenic effects of TGF-β1 in normal human dermal fibroblasts (NHDF). Methods NHDF were exposed to TGF-β1 to establish a fibrotic phenotype. Proliferation rate and cell number were measured using the IncuCyte® Live Cell Imager system and the trypan blue dye exclusion test. Phenoconversion markers (α-SMA and fibronectin) and collagen I levels were assessed by western blot and immunofluorescence. The mRNA levels of TGF-β1 were evaluated by RT-PCR. The Smad2/3 phosphorylation level as well as β-catenin and PPARγ expression, were assessed by western blot. The cell contractility function and migration of NHDF were studied using collagen gel retraction assay, and scratch wound healing assay, respectively. The effects of S. thermophilus lysate, alone or combined with TGF-β1, were evaluated on all of the above-listed parameters and markers associated with TGF-β1-induced fibrotic phenotype. Results Exposure to the S. thermophilus lysate significantly reduced the key mediators and events involved in the abnormal activation of myofibroblasts by TGF-β1 within the fibrotic profile. The S. thermophilus treatment significantly reduced cell proliferation, migration, and myo-differentiation. In addition, the treatment with probiotic lysate reduced the α-SMA, fibronectin, collagen-I expression levels, and affected the collagen contraction ability of activated dermal fibroblasts. Moreover, the probiotic targeted the TGF-β1 signaling, reducing Smad2/3 activation, TGF-β1 mRNA level, and β-catenin expression through the upregulation of PPARγ. Conclusion This is the first report showing that S. thermophilus lysate had a remarkable anti-fibrotic effect in TGF-β1-activated NHDF by inhibiting Smad signaling. Notably, the probiotic was able to reduce β-catenin and increase PPARγ levels. The findings support our point that S. thermophilus may help prevent or treat hypertrophic scarring and keloids. 

https://journal-inflammation.biomedcentral.com/counter/pdf/10.1186/s12950-022-00324-9

Efficacy of probiotic Streptococcus thermophilus in counteracting TGF-β1-induced fibrotic response in normal human dermal fibroblasts

Hypoxia-inducible factor-1α (HIF-1α), a central player in maintaining gut-microbiota homeostasis, plays a pivotal role in inducing adaptive mechanisms to hypoxia and is negatively regulated by prolyl hydroxylase 2 (PHD2). HIF-1α is stabilized through PI3K/AKT signaling regardless of oxygen levels. Considering the crucial role of the HIF pathway in intestinal mucosal physiology and its relationships with gut microbiota, this study aimed to evaluate the ability of the lysate from the multi-strain probiotic formulation SLAB51 to affect the HIF pathway in a model of in vitro human intestinal epithelium (intestinal epithelial cells, IECs) and to protect from lipopolysaccharide (LPS) challenge. The exposure of IECs to SLAB51 lysate under normoxic conditions led to a dose-dependent increase in HIF-1α protein levels, which was associated with higher glycolytic metabolism and L-lactate production. Probiotic lysate significantly reduced PHD2 levels and HIF-1α hydroxylation, thus leading to HIF-1α stabilization. The ability of SLAB51 lysate to increase HIF-1α levels was also associated with the activation of the PI3K/AKT pathway and with the inhibition of NF-κB, nitric oxide synthase 2 (NOS2), and IL-1β increase elicited by LPS treatment. Our results suggest that the probiotic treatment, by stabilizing HIF-1α, can protect from an LPS-induced inflammatory response through a mechanism involving PI3K/AKT signaling.

/pdf/bacterial-lysate-from-the-multi-strain-probiotic-slab51-2twj1rtj.pdf

Bacterial Lysate from the Multi-Strain Probiotic SLAB51 Triggers Adaptative Responses to Hypoxia in Human Caco-2 Intestinal Epithelial Cells under Normoxic Conditions and Attenuates LPS-Induced Inflammatory Response

Infantile colic is a functional gastrointestinal disorder in which a healthy infant displays paroxysms of intense crying or fussiness. Although this condition is self-limited, it causes significant distress for parents and may be linked to long-term health concerns for children. The microbiome of infants with colic has been correlated with increased dysbiosis or imbalance of commensal bacteria. This dysbiosis may ultimately lead to changes in infants’ immunological profiles, favoring markers linked to inflammation, including specific cytokines, calprotectin, and genetic markers. Therapeutic regimens such as probiotics may be helpful in modifying the gut microbial composition, thereby influencing the presence of inflammatory markers and potentially reducing colic symptoms in infants. This review provides a summary of the findings from 10 randomized, placebo-controlled, double-blinded studies conducted in the past five years with the aim of examining the potential therapeutic benefits of probiotics in infantile colic. The articles were selected through PubMed and Google Scholar using the keywords infantile colic, microbiome, probiotics, cytokines, dysbiosis, inflammatory markers, and lactobacilli. We summarize the results of these studies to explore the potential anti-inflammatory therapeutic benefits of single and multi-strain probiotic formulations on daily crying time and key inflammatory markers in infants with colic. The research largely shows the beneficial role of probiotics, largely of the lactobacillus genus, in the reduction of colic symptoms and the reduction of key inflammatory markers. However, some studies demonstrated an insignificant effect of certain probiotic strains in symptom management. Further research is necessary to better understand the anti-inflammatory properties of probiotics and determine the role this could have on the manifestation of colic in infants.

/pdf/the-therapeutic-benefits-of-single-and-multi-strain-2huta120.pdf

The Therapeutic Benefits of Single and Multi-Strain Probiotics on Mean Daily Crying Time and Key Inflammatory Markers in Infantile Colic

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Efficacy of probiotic Streptococcus thermophilus in counteracting TGF-β1-induced fibrotic response in normal human dermal fibroblasts

Bacterial Lysate from the Multi-Strain Probiotic SLAB51 Triggers Adaptative Responses to Hypoxia in Human Caco-2 Intestinal Epithelial Cells under Normoxic Conditions and Attenuates LPS-Induced Inflammatory Response

The Therapeutic Benefits of Single and Multi-Strain Probiotics on Mean Daily Crying Time and Key Inflammatory Markers in Infantile Colic