Bifidobacterium lactis CCT 7858 Improves Gastrointestinal Symptoms by Antibiotics Treatment: a Double-Blind, Randomized, Placebo-Controlled Trial.

Diarrhea is one of the most frequent side effects of antibiotic treatment and occurs in 25 to 40% of patients in use. One potential strategy to prevent this side effect is the concurrent use of probiotics. This study evaluated the efficacy of the strain Bifidobacterium lactis CCT 7858 in the prevention of diarrhea and improvement of gastrointestinal symptoms in hospitalized patients using antibiotics. This was a randomized, blinded, placebo-controlled clinical trial. This study included 104 patients in antibiotic treatment. Patients were randomized into two groups: placebo (maltodextrin) and intervention (strain Bifidobacterium lactis CCT 7858 at 9 × 1010 CFU concentration; GABBIA® Biotecnology, Santa Catarina, Brazil). Patients were supplemented depending on the duration of antibiotic therapy, and both were evaluated with scales in two moments: before and after treatment. We included 104 hospitalized patients. In follow-up, 38 (74.5%) of the B. lactis group have no reported diarrhea. In secondary outcomes, in five day strong abdominal distension was reported in 4 (7,3) placebo group and not reported in B. lactis. Abdominal noises, nausea, and vomiting were not registered in any group. B. lactis strain has been considered safe and with several benefits, including reduction of soft stools and gastrointestinal symptoms how abdominal noise, pain and distension, as well reduction of diarrhea.

Comparative effects of fresh and sterile fecal microbiota transplantation in an experimental animal model of necrotizing enterocolitis.

INTRODUCTION: Necrotizing Enterocolitis (NEC) is a serious intestinal disease that affects premature neonates, causing high mortality, despite the technological development in neonatal intensive care, with antibiotics, parenteral nutrition, surgery, and advanced life support. The correction of dysbiosis with fecal microbiome transplantation (FMT) has shown beneficial effects in experimental models of the disease. The different forms of administration and conservation of FMT and mixed results depending on several factors lead to questions about the mechanism of action of FMT. This study aimed to compare the effectiveness of fresh, sterile FMT and probiotic treatment under parameters of inflammation, oxidative stress, and tissue damage in a neonatal model of NEC. METHODS: One-day-old Wistar rats were used to induce NEC model. Animals were divided in five groups: Control + saline; NEC + saline; NEC + fresh FMT; NEC + sterile FMT and NEC+ probiotics. Parameters of inflammatory response and oxidative damage were measured in the gut, brain, and serum. It was also determined gut histopathological alterations. RESULTS: Proinflammatory cytokines were increased in the NEC group, and IL-10 levels decreased in the gut, brain, and serum. Fresh and sterile FMT decreased inflammation when compared to the use of probiotics. Oxidative and histological damage to the intestine was apparent in the NEC group, and both FMT treatments had a protective effect. CONCLUSION: Fresh and sterile FMT effectively reduced the inflammatory response, oxidative damage, and histological alterations in the gut and brain compared to an experimental NEC model.

Effects of different probiotic strains B. lactis, L. rhamnosus and L. reuteri on brain-intestinal axis immunomodulation in an endotoxin-induced inflammation.

The study evaluated the effects of supplementation with three different probiotic strains Bifidobacterium lactis (LACT GB™), Lactobacillus rhamnosus (RHAM GB™) and Lactobacillus reuteri (REUT GB™) on brain-intestinal immunomodulation in an animal model of LPS-induced inflammation. Fifty mice Balb/C were distributed into five groups: control; lipopolysaccharide (LPS); LPS + B. lactis (LACT GB™); LPS + L. rhamnosus (RHAM GB™); and LPS + L. reuteri (REUT GB™). The animals were supplemented with their respective probiotic microorganisms daily, for 30 days, at a concentration of 1 × 109 CFU/animal/day. After 30 days of supplementation, animals received the inflammatory insult by LPS (15 mg/kg). Behavioral tests, oxidative stress and inflammation were performed, as well as gut and brain histology. In the behavioral test, LPS + B. lactis group was less anxious than the other groups. Serum interleukin IL-1ß and IL-6 levels increased in all groups that received the LPS insult, and there was a reduction in inflammation in the supplemented groups when compared to the LPS group in brain and gut. There is a reduction in myeloperoxidase activity and oxidative stress in groups supplemented with probiotics. In intestine histological analysis occurs damage to the tissue integrity in the LPS group, in the other hand, occurs preservation of integrity in the probiotic supplemented animals. In the brain, infiltrates of perivascular inflammatory cells can be seen in the LPS group. The three probiotic studies showed efficient immunomodulating activity and ensured integrity of the intestinal barrier function, even after the severe insult by LPS. These results show the important role of probiotics in the gut-brain axis. Graphical abstract illustratively represents the gut-brain axis and how different probiotic strains influence the immunomodulatory response releasing different pro- and anti-inflammatory cytokines, and their role in the balance of dysbiosis.

Effects of obesity on neuroinflammatory and neurochemical parameters in an animal model of reserpine-induced Parkinson's disease.

Obesity is associated with low-grade chronic inflammation and oxidative stress, affecting the brain's reward system by decreasing dopaminergic neurotransmission. It is known that dopaminergic neurotransmission is also reduced in Parkinson's disease (PD), and high adiposity is considered a risk factor for the development of several neurodegenerative diseases, including PD. This study aimed to assess the effects of obesity on neuroinflammatory and neurochemical parameters in an animal model of reserpine-induced PD. The obese group showed increased inflammation and oxidative damage as well as inhibition of mitochondrial respiratory chain complexes I and II and DNA damage in the evaluated structures. The PD group did not show inflammation or mitochondrial dysfunction but exhibited oxidative damage in the hippocampus. The combination group (obesity + PD) showed reduced inflammation and oxidative stress and increased activity of complexes I and II of the mitochondrial respiratory chain in most of the analyzed structures. On the other hand, obesity + PD caused oxidative damage to proteins in the liver, prefrontal cortex, striatum, and cerebral cortex and oxidative stress in the hypothalamus, resulting in reduced catalase activity. Furthermore, the combination group showed DNA damage in blood, liver, and cerebral cortex. In conclusion, it was observed that the association of obesity and PD did not increase inflammation, oxidative stress, or mitochondrial dysfunction in most of the evaluated structures but increased oxidative damage and induced mechanisms that led to DNA damage in peripheral tissues and brain structures.

Microglial Cells Depletion Increases Inflammation and Modifies Microglial Phenotypes in an Animal Model of Severe Sepsis.

Sepsis-associated encephalopathy is highly prevalent and has impact both in early and late morbidity and mortality. The mechanisms by which sepsis induces brain dysfunction include neuroinflammation, disrupted blood-brain barrier, oxidative stress, and microglial activation, but the cellular and molecular mechanisms involved in these events are not completely understood. Our objective was to determine the effects of microglial depletion in the early systemic and brain inflammatory response and its impact in phenotypes expression in an animal model of sepsis. Animals were subjected to CLP, and depletion of microglial cells was accomplished by administration of (Lipo)-encapsulated clodronate and microglial repopulation by doxycycline. Clod-lip treatment was effective in decreasing microglia density in the hippocampus of animals. Pro-inflammatory cytokines were increased in the CLP+PBS, and liposomes administration increased even further these cytokines mainly 7 days, suggesting that microglial depletion exacerbates both local and systemic inflammation. In contrast, repopulation with doxycycline was able to revert the cytokine levels in both serum and cerebral structures on day 7 and 14 after repopulation. There were no differences in the correlation between M1 and M2 markers by real-time PCR, but immunohistochemistry showed significant increase in CD11b expression in CLP+PBS with greater expression in CLP + liposomes in the hippocampus. These results suggest that the depletion of microglia during severe sepsis development could be associated with early exacerbation of brain and systemic inflammation and repopulation is able to revert this condition, once a rapid neurological recovery is noticed until 7 days after sepsis.

The additive effect of aging on sepsis-induced cognitive impairment and neuroinflammation.

Systemic inflammation is emerging as a significant driver of cognitive decline in the aged and vulnerable brain. In sepsis survivors animals low-grade brain inflammation occurs, suggesting that sepsis is able to induce in microglia a primed-like state. The purpose of this study is to analyze the role of sepsis-induced brain inflammation in the progression of the physiological process of brain aging. Wistar rats 2month-old were subjected to sepsis and 60 and 90days after were submitted to the new object recognition test and brain was removed to the determination of cytokines, myeloperoxidase (MPO) activity, amyloid-beta peptide (Aß) and immunohistochemistry markers of microglial activation. In the hippocampus, from 60 to 90days there was an increase in TNF-α and IL-1ß levels in septic animals. This also occurred to the levels of IL-1ß and IL-6 in the prefrontal cortex. This was associated with persistent increased in microglial activation and Aß levels. In conclusion, neuroinflammation is persistent after sepsis and this could burst the usual inflammation that occurs during brain aging.