Microbial network signatures of early colonizers in infants with eczema.

In this longitudinal cohort study, our results demonstrated that there are rhythmic changes in gut microbial network signatures in early life, and healthy infants adopt more complex and stable network structure in their gut microbiota than that of the infants with eczema.

Lactobacillus plantarum Lp3a improves functional constipation: evidence from a human randomized clinical trial and animal model.

Background: Functional constipation (FC) is a common gastrointestinal (GI) disorder characterized by symptoms of constipation without a clear physiologic or anatomic cause. Gut microbiome dysbiosis has been postulated to be a factor in the development of FC, and treatment with probiotic regimens, including strains of Lactobacillus plantarum (L. plantarum), has demonstrated efficacy in managing symptoms. To further understand the role of L. plantarum in GI health, we conducted an animal study and a randomized, double-blind, placebo-controlled clinical trial to evaluate the effect of a specific sub-strain, Lp3a, on FC. Methods: For the animal study, male Kunming mice were treated with doses of L. plantarum Lp3a ranging from 0.67 to 2.00 g/kg or an equivalent amount of placebo for 15 days prior to the induction of constipation via 20 mL/kg of 25% diphenoxylate solution. GI motility parameters including intestinal motion and stool amount were then assessed. In the human study, 120 patients with FC were randomized to treatment [L. plantarum Lp3a; 2×1.0×1010 (colony forming units; CFU) ×7 days] or control groups (n=60 each). The primary endpoint was survey information on FC signs/symptoms. Participants and observers were blinded to group allocation. A subset of 20 Lp3a treated patients underwent pre- and post-treatment 16 s ribosomal ribonucleic acid (rRNA) gene sequencing. Whole genome sequencing (WGS) of L. plantarum Lp3a was also performed. Results: Lp3a-treated mice showed significantly improved intestinal motion, reduced time to first defecation, and increased stool amounts. Similarly, patients in the treatment group (n=59) reported significant improvements in FC signs/symptoms compared to controls (n=58; all P<0.05). Although 16 s rRNA sequencing revealed no significant variations between pre- and post-treatment samples, WGS of Lp3a itself revealed several biological pathways that may underlie the relief of FC symptoms in animals and humans, including methane and fatty acid metabolism and bile acid biosynthesis. Conclusions: We found that the use of the novel probiotic sub-strain, L. plantarum Lp3a, led to clinically significant improvements in FC in both mice and humans, and identified the potential biological mechanisms underlying this activity.

A Novel Probiotic Formula, BIOCG, Protects Against Alzheimer's-Related Cognitive Deficits via Regulation of Dendritic Spine Dynamics.

BACKGROUND: The brain-gut-microbiome axis has emerged as an important pathway through which perturbations in the gut and/or microbial microenvironment can impact neurological function. Such alterations have been implicated in a variety of neuropsychiatric disorders, including depression, anxiety, and Alzheimer's Disease (AD) and the use of probiotics as therapy for these diseases remains promising. However, the mechanisms underlying the gut microenvironment's influence on disease pathogenesis and therapy remain unclear. OBJECTIVE: The objective of this study is to investigate the effect of a novel probiotic formula, BIOCG, on cognitive function and pathobiological mechanisms, including amyloid processing and dendritic spine dynamics, in a mouse model of AD. METHODS: BIOCG was administered for 3 months to 3xTg or 3xTg; Thy1-YFP AD mice and functional outcomes were assessed via behavioral testing and electrophysiology. Mechanisms relevant to AD pathogenesis including dendritic spine morphology and turnover, Amyloid Precursor Protein (APP) processing and microglial phenotype were also evaluated. Finally, we sequenced fecal samples following probiotic treatment to assess the impact on gut microbial composition and correlate the changes with the above described measures. RESULTS: Mice treated with BIOCG demonstrated preserved cognitive abilities and stronger Long- Term Potentiation (LTP), spontaneous Excitatory Postsynaptic Currents (sEPSC), and glutamate-induced LTPs, indicative of functional and electrophysiological effects. Moreover, we observed attenuated AD pathogenesis, including reduced Amyloid Beta (Aß) burden, as well as more mature dendritic spines in the BIOCG-treated. Our finding of changes in microglial number and phenotype in the treatment group suggests that this formulation may mediate its effects via attenuation of neuroinflammation. Sequencing data confirmed that the gut microbiome in treated mice was more varied and harbored a greater proportion of "beneficial" bacteria. CONCLUSION: Overall, our results indicate that treatment with BIOCG enhances microbial diversity and, through gut-brain axis interactions, attenuates neuroinflammation to produce histologic and functional improvement in AD pathogenesis.

Maternal Benzophenone Exposure Impairs Hippocampus Development and Cognitive Function in Mouse Offspring.

Benzophenones are widely supplemented in personal care products, but little is known about its neurodevelopmental toxicity. The previous epidemiological study discovered a negative correlation between maternal exposure to a benzophenone metabolite 4-hydroxybenzophenone (4HBP) and child's neurodevelopment, yet the causal relationship and detailed mechanism remain to be defined. Here, it is reported that prenatal, but not postnatal, exposure to environmentally relevant level of 4HBP impairs hippocampus development and causes cognitive dysfunction in offspring mice. Transcriptomic analyses reveal that 4HBP induces the endoplasmic reticulum stress-induced apoptotic signaling and inflammatory response in hippocampal neural stem cells. Mechanistically, 4HBP exposure activates protein kinase R-like ER kinase (PERK) signaling, which induces CHOP, inhibits IκB translation, and transactivates p65, thereby promoting inflammation and apoptosis on multiple levels. Importantly, genetic or pharmacological inhibition of PERK pathway significantly attenuates 4HBP-induced NFκB signaling and neurodevelopmental abnormalities in mice and in a human brain organoid model. The study uncovers the neurodevelopmental toxicity of BP and cautions its exposure during pregnancy.

Postsynthesis Strategy of Functional Zn-MOF Sensors for the Detection of ClO- and DPA.

Active species were introduced into MOFs to prepare multifunctional fluorescent probes by a stepwise postsynthetic modulation strategy. First, two-dimensional HPU-16 (HPU = Henan Polytechnic University; HPU-16 = Zn(L)2(H2O); HL = 2-(5-pyridin-4-yl-5H-[1,2,4]triazol-3-yl)-pyrazine) was transformed into three-dimensional HPU-17 ({Zn3(L)2(btc)2(H2O)}n) through a crystal dissolution-recrystallization process. Second, linker replacement was used to introduce -NH2 into the HPU-17 to generate functional NH2-HPU-17 via a single-crystal to single-crystal transformation. The functional amino groups caused NH2-HPU-17 to show a significant response to ClO-. Because of the interaction of amino groups and ClO-, the fluorescence of NH2-HPU-17 gradually changed from blue to yellow-green. More interestingly, NH2-HPU-17 could encapsulate Tb3+ and sensitize the visible-emitting characteristic fluorescence of Tb3+ in aqueous solution. Then, newly generated Tb3+@NH2-HPU-17 could serve as an effective probe for the determination of DPA. This work paves a new way for the design and modulation of ratiometric fluorescence probes for the selective and sensitive detection of special molecules.