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      Probiotic Lactobacillus rhamnosus GG improves insulin sensitivity and offspring survival via modulation of gut microbiota and serum metabolite in a sow model

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          Abstract

          Background

          Sows commonly experience insulin resistance in late gestation and lactation, causing lower feed intake and milk production, which can lead to higher mortality rates in newborn piglets. The probiotic Lactobacillus rhamnosus GG (LGG) is known to improve insulin resistance. However, whether supplementing LGG can improve insulin sensitivity in sows and enhance lactation performance, particularly the early survival of offspring remains unclear. Hence, we explored the effects and mechanisms of supplementing LGG during late gestation and lactation on sow insulin sensitivity, lactation performance, and offspring survival. In total, 20 sows were randomly allocated to an LGG ( n = 10) and control group ( n = 10).

          Results

          In sows, LGG supplementation significantly improved insulin sensitivity during late gestation and lactation, increased feed intake, milk production and colostrum lactose levels in early lactation, and enhanced newborn piglet survival. Moreover, LGG treatment significantly reshaped the gut microbiota in sows, notably increasing microbiota diversity and enriching the relative abundance of insulin sensitivity-associated probiotics such as Lactobacillus, Bifidobacterium, and Bacteroides. Serum metabolite and amino acid profiling in late-gestation sows also revealed decreased branched-chain amino acid and kynurenine serum levels following LGG supplementation. Further analyses highlighted a correlation between mitigated insulin resistance in late pregnancy and lactation by LGG and gut microbiota reshaping and changes in serum amino acid metabolism. Furthermore, maternal LGG enhanced immunity in newborn piglets, reduced inflammation, and facilitated the establishment of a gut microbiota.

          Conclusions

          We provide the first evidence that LGG mitigates insulin resistance in sows and enhances offspring survival by modulating the gut microbiota and amino acid metabolism.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s40104-024-01046-z.

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          Most cited references62

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          Dose translation from animal to human studies revisited.

          As new drugs are developed, it is essential to appropriately translate the drug dosage from one animal species to another. A misunderstanding appears to exist regarding the appropriate method for allometric dose translations, especially when starting new animal or clinical studies. The need for education regarding appropriate translation is evident from the media response regarding some recent studies where authors have shown that resveratrol, a compound found in grapes and red wine, improves the health and life span of mice. Immediately after the online publication of these papers, the scientific community and popular press voiced concerns regarding the relevance of the dose of resveratrol used by the authors. The animal dose should not be extrapolated to a human equivalent dose (HED) by a simple conversion based on body weight, as was reported. For the more appropriate conversion of drug doses from animal studies to human studies, we suggest using the body surface area (BSA) normalization method. BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function. We advocate the use of BSA as a factor when converting a dose for translation from animals to humans, especially for phase I and phase II clinical trials.
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            Human gut microbes impact host serum metabolome and insulin sensitivity.

            Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.
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              Towards a better understanding of Lactobacillus rhamnosus GG - host interactions

              Lactobacillus rhamnosus GG (LGG) is one of the most widely used probiotic strains. Various health effects are well documented including the prevention and treatment of gastro-intestinal infections and diarrhea, and stimulation of immune responses that promote vaccination or even prevent certain allergic symptoms. However, not all intervention studies could show a clinical benefit and even for the same conditions, the results are not univocal. Clearly, the host phenotype governed by age, genetics and environmental factors such as the endogenous microbiota, plays a role in whether individuals are responders or non-responders. However, we believe that a detailed knowledge of the bacterial physiology and the LGG molecules that play a key role in its host-interaction capacity is crucial for a better understanding of its potential health benefits. Molecules that were yet identified as important factors governing host interactions include its adhesive pili or fimbriae, its lipoteichoic acid molecules, its major secreted proteins and its galactose-rich exopolysaccharides, as well as specific DNA motifs. Nevertheless, future studies are needed to correlate specific health effects to these molecular effectors in LGG, and also in other probiotic strains.
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                Author and article information

                Contributors
                ZFang@sicau.edu.cn
                Journal
                J Anim Sci Biotechnol
                J Anim Sci Biotechnol
                Journal of Animal Science and Biotechnology
                BioMed Central (London )
                1674-9782
                2049-1891
                2 July 2024
                2 July 2024
                2024
                : 15
                : 89
                Affiliations
                [1 ]Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, ( https://ror.org/0388c3403) 211 Huimin Road, Wenjiang District, Chengdu, 611130 China
                [2 ]GRID grid.80510.3c, ISNI 0000 0001 0185 3134, Key Laboratory of Agricultural Product Processing and Nutrition Health (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Food Science, , Sichuan Agricultural University, ; Ya’ an, 625014 China
                Author information
                http://orcid.org/0000-0003-1844-194X
                Article
                1046
                10.1186/s40104-024-01046-z
                11218078
                38951898
                202b1043-9e19-41b3-b5e4-9cbaf1eb7379
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 15 February 2024
                : 7 May 2024
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 31972603
                Award Recipient :
                Categories
                Research
                Custom metadata
                © Chinese Association of Animal Science and Veterinary Medicine 2024

                Animal science & Zoology
                gut microbiota,insulin resistance,lactobacillus rhamnosus gg,lactation performance,piglet,sow

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