JP-2022535761-A5 -

Dates

Publication Date

20230512

Application Date

20200603

Description

This invention was developed with government support under grant number GM123482 from the National Institutes of Health . The U.S. Government has certain rights to this invention. Sequence List In some embodiments, kits are provided that include, or alternatively consist essentially of, or otherwise comprise the compositions described herein and instructions for use in diagnostic, industrial, agricultural, or therapeutic applications. In certain embodiments, for example, the following items are provided: (Item 1) A method for preventing, delaying, or treating neurodevelopmental disorders or promoting neurodevelopment in a subject who is suffering from, susceptible to, or has suffered from neurodevelopmental disorders, comprising the step of administering to the subject an effective amount of a composition comprising microspheres, biofilm-forming probiotic bacteria and prebiotics, wherein the prebiotics comprises a nutrient supplement for the probiotic bacteria, and optionally, the subject is suffering from NEC or other conditions that similarly affect the brain, or sepsis and/or conditions that cause sepsis. (Item 2) A method for preventing, reducing, or delaying the activation of microglia in a subject, comprising the step of administering to the subject an effective amount of a composition comprising microspheres, biofilm-forming probiotic bacteria, and prebiotics, wherein the prebiotics comprises a nutrient supplement for the probiotic bacteria. (Item 3) The method according to item 2, wherein the thickness of the microglial cell body is reduced in the subject compared to the control subject. (Item 4) The method according to item 1 or 2, wherein the dendritic structures of microglia are thinned in the subject compared to a control subject. (Item 5) A method for increasing the expression of brain-derived neurotrophic factor (BDNF) in a subject, comprising the step of administering to the subject an effective amount of a composition comprising microspheres, biofilm-forming probiotic bacteria, and prebiotics, wherein the prebiotics comprises a nutrient supplement for the probiotic bacteria. (Item 6) The method according to item 5, wherein the increase is an increase compared to a control. (Item 7) The method according to item 5 or 6, wherein the increase in BDNF expression is an increase in expression within the hippocampus of the subject. (Item 8) A method for increasing the expression of Grin2A in a subject, comprising the step of administering to the subject an effective amount of a composition comprising microspheres, biofilm-forming probiotic bacteria, and prebiotics, wherein the prebiotics comprises a nutrient supplement for the probiotic bacteria. (Item 9) The method according to item 8, wherein the increase is an increase compared to a control. (Item 10) The method according to item 8 or 9, wherein the increase in Grin2A expression is an increase in expression within the prefrontal cortex of the subject. (Item 11) The method according to any one of items 1 to 10, wherein the microsphere further comprises a partial or complete biofilm coating on the outer surface of the microsphere. (Item 12) The method according to any one of items 1 to 11, wherein the bacteria and the prebiotics diffuse from inside the microsphere to the surface of the microsphere. (Item 13) The method according to any one of items 1 to 12, wherein the microspheres comprise a material selected from the group consisting of biodegradable polymers, non-degradable polymers, and metals, and the diameter of the microspheres is about 0.5 micrometers to about 1000 micrometers. (Item 14) The method according to any one of items 1 to 13, wherein the composition further comprises one or more of prebiophilic compounds, therapeutic agents or therapeutic agents, chemical reducing agents, molecules that promote adsorption, and molecules that support absorption. (Item 15) The method according to item 14, wherein the prebiofirmics include agents that support the formation and persistence of biofilms. (Item 16) The method according to item 15, wherein the prebiofermics is a DNA-binding polypeptide or protein, and/or a DNABII polypeptide or protein, or an equivalent thereof. (Item 17) The method according to any one of items 1 to 16, wherein the prebiotics include water-soluble carbohydrates, inulin, oligosaccharides, oligofructose, fructooligosaccharides, galactooligosaccharides, glucose, starch, maltose, maltodextrin, polydextrose, amylose, sucrose, fructose, lactose, isomaltulose, polyols, glycerol, carbonate, thiamine, choline, histidine, trehalose, nitrogen, sodium nitrate, ammonium nitrate, phosphorus, phosphate, hydroxyapatite, potassium, potassium, sulfur, homopolysaccharides, heteropolysaccharides, cellulose, chitin, vitamins, and combinations thereof. (Item 18) The method according to any one of items 1 to 17, wherein the composition further comprises a pharmaceutically acceptable carrier or biocompatible scaffold. (Item 19) The probiotic b