Precision microbiome programming for therapeutic applications is limited by challenges in achieving reproducible colonic colonization. Previously, we created an exclusive niche in which to engraft engineered bacteria into diverse microbiota in mice by using a porphyran prebiotic. Building on this approach, we engineered conditional attenuation into a porphyran-utilizing strain of Phocaeicola vulgatus by replacing native essential gene regulation with a porphyran-inducible promoter to allow reversible engraftment. Engineering a five-gene oxalate degradation pathway into the reversibly engrafting strain resulted in a therapeutic candidate that reduces hyperoxaluria, a cause of kidney stones, in preclinical models. Our Phase 1/2a clinical trial demonstrated porphyran dose-dependent abundance and reversible engraftment in humans, reduction of oxalate in the urine, as well as genetic stability challenges to achieving long-term treatment.

Obesity is a complex disease that increases the risk of other pathologies. Its prevention and long-term weight loss maintenance are problematic. Gut microbiome is considered a potential obesity modulator. The objective of the present study was to summarize recent findings regarding the relationships between obesity, gut microbiota, and diet (vegetable/animal proteins, high-fat diets, restriction of carbohydrates), with an emphasis on dietary fiber and resistant starch. The composition of the human gut microbiome and the methods of its quantification are described. Products of the gut microbiome metabolism, such as short-chain fatty acids and secondary bile acids, and their effects on the gut microbiota, intestinal barrier function and immune homeostasis are discussed in the context of obesity. The importance of dietary fiber and resistant starch is emphasized as far as effects of the host diet on the composition and function of the gut microbiome are concerned. The complex relationships between human gut microbiome and obesity are finally summarized.

<h4>Background and aim</h4>The pursuit of sustainable alternatives to antibiotic growth promoters has intensified interest in spore-forming probiotics with fiber-degrading capabilities. This study aimed to isolate, characterize, and evaluate the safety and functional properties of <i>Bacillus</i> spp. from native Thai swine, focusing on strains with probiotic potential and enzymatic activity for application in livestock nutrition.<h4>Materials and methods</h4>Spore-forming <i>Bacillus</i> isolates were obtained from fecal samples of backyard-raised native pigs. Isolates were screened for acid and bile tolerance, autoaggregation, hydrophobicity, biofilm formation, adhesion to Caco-2 cells, antimicrobial activity, and co-aggregation with pathogens. Enzyme production (cellulase, xylanase, and pectinase), hemolytic activity, and antibiotic susceptibility were also assessed. The most promising strain, <i>Bacillus amyloliquefaciens</i> NL1.2, was subjected to <i>in vivo</i> safety and efficacy evaluations in a mouse model, including assessments of toxicity, histopathology, secretory immunoglobulin A (IgA) levels, and gut microbiome modulation through full-length 16S ribosomal RNA sequencing.<h4>Results</h4><i>B. amyloliquefaciens</i> NL1.2 exhibited robust probiotic traits including high acid (115.05%) and bile (75.16%) tolerance, strong autoaggregation (65.99%), moderate hydrophobicity (34.13%), and effective adhesion (2.0%) to intestinal epithelial cells. It produced fiber-degrading enzymes (cellulase: 0.015 U/mL; xylanase: 0.522 U/mL; and pectinase: 0.374 U/mL) showed antimicrobial activity against <i>Enterohemorrhagic Escherichia coli</i>, <i>Enteropathogenic E. coli</i>, and <i>Salmonella</i> Typhimurium, and was non-hemolytic and antibiotic-sensitive. <i>In vivo</i>, NL1.2 induced no adverse effects and significantly elevated intestinal secretory IgA levels (p < 0.05). Microbiome analysis revealed enrichment of beneficial taxa (e.g., <i>Bacteroidetes</i> and <i>Barnesiella</i>) and reduction of potentially pathogenic taxa (e.g., <i>Helicobacter</i> and <i>Deferribacteres</i>).<h4>Conclusion</h4><i>B. amyloliquefaciens</i> NL1.2 is a safe, multifunctional probiotic with fiber-degrading, immunomodulatory, and gut microbiota-modulating properties. Its origin from native swine and broad functional attributes highlights its potential as a next-generation feed additive for sustainable animal production.

Implantation and development of the gut flora in the newborn animal. The newborn mammal, germfree in the mother's uterus, steps in complex microbial environment as soon as born. Bacterial development in the digestive cavities of the newborn animal, from the environmental bacteria, occurs very quickly. Within three hours after birth a small microbial population is present in the piglet, baby mouse or human baby. Within twelve hours after birth, dominant microbial population of the newborn animal can be as important as that of the adult animal. In any case, this highest level is reached within 24 h after birth. Studying several animal species, one observes a certain diversity in the steps of establishment of the principal bacterial groups. For instance, facultative anaerobic bacteria appear before strictly anaerobic bacteria in the young mouse, whereas the opposite situation happens in the young hare. In the calf and the piglet, strictly and facultative bacteria establish approximatively at the same time. On day one after birth E. coli and Streptococci establish in the human infant, and also species belonging to genus Bacteroides and Bifidobacterium.

Lactic acid bacteria in the gut in normal and disordered states. The human gut flora is a complex and finely balanced ecosystem which plays an important protective role in humans. Although relatively stable, its composition may be altered in various disease states and by the administration of antimicrobial agents. Preparations containing viable lactic acid bacteria of human origin appear to have value in restoring normal microbial function and alleviating symptoms in some patients with gastrointestinal infection and other conditions. Published in Digestive diseases (Basel, Switzerland) (1992)