Lactobacillus Strains Alleviated Hyperlipidemia and Liver Steatosis in Aging Rats via Activation of AMPK.

In this study, we hypothesized that different strains of Lactobacillus can alleviate hyperlipidemia and liver steatosis via activation of 5' adenosine monophosphate-activated protein kinase (AMPK), an enzyme that is involved in cellular energy homeostasis, in aged rats. Male rats were fed with a high-fat diet (HFD) and injected with D-galactose daily over 12 weeks to induce aging. Treatments included (n = 6) (i) normal diet (ND), (ii) HFD, (iii) HFD-statin (lovastatin 2 mg/kg/day), (iv) HFD-Lactobacillus fermentum DR9 (10 log CFU/day), (v) HFD-Lactobacillus plantarum DR7 (10 log CFU/day), and (vi) HFD-Lactobacillus reuteri 8513d (10 log CFU/day). Rats administered with statin, DR9, and 8513d reduced serum total cholesterol levels after eight weeks (p < 0.05), while the administration of DR7 reduced serum triglycerides level after 12 weeks (p < 0.05) as compared to the HFD control. A more prominent effect was observed from the administration of DR7, where positive effects were observed, ranging from hepatic gene expressions to liver histology as compared to the control (p < 0.05); downregulation of hepatic lipid synthesis and ß-oxidation gene stearoyl-CoA desaturase 1 (SCD1), upregulation of hepatic sterol excretion genes of ATP-binding cassette subfamily G member 5 and 8 (ABCG5 and ABCG8), lesser degree of liver steatosis, and upregulation of hepatic energy metabolisms genes AMPKα1 and AMPKα2. Taken altogether, this study illustrated that the administration of selected Lactobacillus strains led to improved lipid profiles via activation of energy and lipid metabolisms, suggesting the potentials of Lactobacillus as a promising natural intervention for alleviation of cardiovascular and liver diseases.

Lactobacillus sp. improved microbiota and metabolite profiles of aging rats.

Aging is closely associated with altered gut function and composition, in which elderly were reported with reduced gut microbiota diversity and increased incidence of age-related diseases. Probiotics have been shown to exert beneficial health-promoting effects through modulation of intestinal microflora biodiversity, thus the effects of probiotics administration on D-galactose (D-gal) senescence-induced rat were evaluated based on the changes in gut microbiota and metabolomic profiles. Upon senescence induction, the ratio of Firmicutes/ Bacteroidetes was significantly lowered, while treatment with Lactobacillus helveticus OFS 1515 and L. fermentum DR9 increased the ratio at the phylum level (P < 0.05). Study on the genus level showed that L. paracasei OFS 0291 and L. helveticus OFS 1515 administration reduced Bacteroides, which are prominently opportunistic pathogens while L. fermentum DR9 treated rats promoted the proliferation of Lactobacillus compared to the aged rats (P < 0.05). Probiotics treatment did not alter fecal short-chain fatty acid (SCFA) profile, but an increase in acetate was observed in the D-gal rats. The analysis of fecal water-soluble metabolites showed that D-gal induced senescence caused great impact on amino acids metabolism such as urocanic acid, citrulline, cystamine and 5-oxoproline, which could serve as potential aging biomarkers. Treatment with probiotics ameliorated these metabolites in a strain-specific manner, whereby L. fermentum DR9 promoted antioxidative effect through upregulation of oxoproline, whereas both L. paracasei OFS 0291 and L. helveticus OFS 1515 restored the levels of reducing sugars, arabinose and ribose similar to the young rats. D-gal induced senescence did cause significant immunological alteration in the colon of aged rats however, all probiotic strains demonstrated immunomodulatory properties as L. paracasei OFS 0291, L. helveticus OFS 1515 and L. fermentum DR9 alleviated proinflammatory cytokines TNF-α, IFN-γ and IL-1ß as well as IL-4 compared to the aged control (P < 0.05). Our study highlights the potential of probiotics as an anti-aging therapy through healthy gut modulation.

Lactobacillus plantarum DR7 improved upper respiratory tract infections via enhancing immune and inflammatory parameters: A randomized, double-blind, placebo-controlled study.

The aims of this study were to investigate the effects of Lactobacillus plantarum DR7 isolated from bovine milk against upper respiratory tract infections (URTI) and elucidate the possible mechanisms underlying immunomodulatory properties. The DR7 strain (9 log cfu/d) was administered for 12 wk in a randomized, double-blind, and placebo-controlled human study involving 109 adults (DR7, n = 56; placebo, n = 53). Subjects were assessed for health conditions monthly via questionnaires, and blood samples were evaluated for cytokine concentrations, peroxidation and oxidative stress, and gene expression in T cells and natural killer (NK) cells. The administration of DR7 reduced the duration of nasal symptoms (mean difference 5.09 d; 95% CI: 0.42-9.75) and the frequency of URTI (mean difference 0.32; 95% CI: 0.01-0.63) after 12 and 4 wk, respectively, compared with the placebo. The DR7 treatment suppressed plasma proinflammatory cytokines (IFN-γ, TNF-α) in middle-aged adults (30 to 60 yr old), while enhancing anti-inflammatory cytokines (IL-4, IL-10) in young adults (<30 yr old), accompanied by reduced plasma peroxidation and oxidative stress levels compared with the placebo. Young adults who received DR7 showed higher expression of plasma CD44 and CD117 by 4.50- and 2.22-fold, respectively, compared with the placebo. Meanwhile, middle-aged adults showed lower expression of plasma CD4 and CD8 by 11.26- and 1.80-fold, respectively, compared with the placebo, indicating less T-cell activation. In contrast, both young and middle-aged adults who received DR7 showed enhanced presence of nonresting and mature NK cells compared with those who received the placebo. We postulate that DR7 alleviated the symptoms of URTI by improving inflammatory parameters and enhancing immunomodulatory properties.

Constipation anti-aging effects by dairy-based lactic acid bacteria.

Constipation, which refers to difficulties in defecation and infrequent bowel movement in emptying the gastrointestinal system that ultimately produces hardened fecal matters, is a health concern in livestock and aging animals. The present study aimed to evaluate the potential effects of dairy-isolated lactic acid bacteria (LAB) strains to alleviate constipation as an alternative therapeutic intervention for constipation treatment in the aging model. Rats were aged via daily subcutaneous injection of D-galactose (600 mg/body weight [kg]), prior to induction of constipation via oral administration of loperamide hydrochloride (5 mg/body weight [kg]). LAB strains (L. fermentum USM 4189 or L. plantarum USM 4187) were administered daily via oral gavage (1 × 10 Log CFU/day) while the control group received sterile saline. Aged rats as shown with shorter telomere lengths exhibited increased fecal bulk and soften fecal upon administration of LAB strains amid constipation as observed using the Bristol Stool Chart, accompanied by a higher fecal moisture content as compared to the control (p < 0.05). Fecal water-soluble metabolite profiles showed a reduced concentration of threonine upon administration of LAB strains compared to the control (p < 0.05). Histopathological analysis also showed that the administration of LAB strains contributed to a higher colonic goblet cell count as compared to the control (p < 0.05). The present study illustrates the potential of dairy-sourced LAB strains as probiotics to ameliorate the adverse effect of constipation amid aging, and as a potential dietary intervention strategy for dairy foods including yogurt and cheese.

Effects of Potential Probiotic Strains on the Fecal Microbiota and Metabolites of D-Galactose-Induced Aging Rats Fed with High-Fat Diet.

Both aging and diet play an important role in influencing the gut ecosystem. Using premature senescent rats induced by D-galactose and fed with high-fat diet, this study aims to investigate the effects of different potential probiotic strains on the dynamic changes of fecal microbiome and metabolites. In this study, male Sprague-Dawley rats were fed with high-fat diet and injected with D-galactose for 12 weeks to induce aging. The effect of Lactobacillus plantarum DR7, L. fermentum DR9, and L. reuteri 8513d administration on the fecal microbiota profile, short-chain fatty acids, and water-soluble compounds were analyzed. It was found that the administration of the selected strains altered the gut microbiota diversity and composition, even at the phylum level. The fecal short-chain fatty acid content was also higher in groups that were administered with the potential probiotic strains. Analysis of the fecal water-soluble metabolites revealed that administration of L. plantarum DR7 and L. reuteri 8513d led to higher fecal content of compounds related to amino acid metabolism such as tryptophan, leucine, tyrosine, cysteine, methionine, valine, and lysine; while administration of L. fermentum DR9 led to higher prevalence of compounds related to carbohydrate metabolism such as erythritol, xylitol, and arabitol. In conclusion, it was observed that different strains of lactobacilli can cause difference alteration in the gut microbiota and the metabolites, suggesting the urgency to explore the specific metabolic impact of specific strains on the host.