The Effects of Recombinant Human Lactoferrin on Immune Activation and the Intestinal Microbiome Among Persons Living with Human Immunodeficiency Virus and Receiving Antiretroviral Therapy

Sortino, Ornella; Hullsiek, Katherine Huppler; Richards, Elizabeth; Rupert, Adam; Schminke, Andrea; Tetekpor, Namo; Quiñones, Mariam; Prosser, Rachel; Schacker, Tim; Sereti, Irini; Baker, Jason V.

doi:10.1093/infdis/jiz042

Cited by 21 publications

(23 citation statements)

References 15 publications

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“…[ 29 ] Generally, an adult can ingest 100 mg of Lf every day, accounting for 1/500 of total protein consumption. The Lf doses in clinical trials ranged from 200 to 3600 mg day −1 , [ 30–35 ] and mainly concentrated in 1 g day −1 , [ 31–34 ] which is equal to decuple daily dose. In the previous studies, the Lf intervention doses were usually very high, [ 12,19,21 ] whereas the effects of Lf at daily dose on disease prevention have not been fully determined.…”

Section: Discussionmentioning

confidence: 99%

Daily Dose of Bovine Lactoferrin Prevents Ethanol‐Induced Liver Injury and Death in Male Mice by Regulating Hepatic Alcohol Metabolism and Modulating Gut Microbiota

Liu

Qian

Yang

et al. 2021

Molecular Nutrition Food Res

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Scope Lactoferrin (Lf) possess a protective potential to liver, but whether it can prevent alcoholic liver injury (ALI) remains unclear. Methods and Results Four groups of male C57BL/6J mice are fed with different diets, namely, AIN‐93G diet for control (CON) and ethanol (EtOH) groups, and AIN‐93G diet with 0.4% and 4% casein replaced by Lf for low‐dose Lf (LLf) and high‐dose Lf (HLf) groups, respectively. ALI is induced by giving 20% ethanol ad libitum combined with four “binges”. Lf can remarkably decrease EtOH‐induced mortality. Lf promotes aldehyde dehydrogenase‐2 (ALDH2) expression and suppressing cytochrome P450 2E1 (CYP2E1) overexpression, resulting in the reduced hepatic superoxide and inflammation levels, which ultimately leads to the hepatic injury alleviation. However, HLf increases acetyl‐CoA carboxylase and fatty acid synthase protein levels, which suggests that excessive intake may weaken the beneficial effects of Lf. Moreover, LLf increases the relative abundances of Akkermansia and Lactobacillus. Additionally, the study shows that Lf likely exerts action in its digestive product forms rather than intact Lf molecular in normal condition. Conclusion LLf can ameliorate ALI, which is associated with the regulation of hepatic alcohol metabolism and the modulation of gut microbiota. However, excessive Lf intake may result in a diminished benefit.

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Section: Discussionmentioning

confidence: 99%

Daily Dose of Bovine Lactoferrin Prevents Ethanol‐Induced Liver Injury and Death in Male Mice by Regulating Hepatic Alcohol Metabolism and Modulating Gut Microbiota

Liu

Qian

Yang

et al. 2021

Molecular Nutrition Food Res

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show abstract

“…Integration with other omics platforms, such as proteomics and transcriptomics, would provide a more comprehensive snapshot of the biological impact of LF supplementation. Otherwise, LF supplementation also alters intestinal immunity [67] and alters intestinal flora [68,69], which may be related to bone health. Future work should include multi-omics validation of these results, focusing on changed metabolites which are related to bone formation in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 99%

Urinary Metabolic Profiling via LC-MS/MS Reveals Impact of Bovine Lactoferrin on Bone Formation in Growing SD Rats

Zhao

Ren

et al. 2020

Nutrients

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Lactoferrin (LF) exerts a promoting bone health function. The effects of LF on bone formation at the metabolic level have been less explored. Urinary metabolic profiling of growing Sprague-Dawley (SD) rats LF-supplemented (1000 mg/kg bw) for four weeks were explored by Liquid chromatography–tandem mass spectrometry (LC-MS/MS). The serum markers of bone formation and bone resorption, the bone mass, and the osteogenesis markers of femur were measured by an enzyme-linked immunosorbent assay, micro-computerized tomography, and immunohistochemistry, respectively. Compared with the control, LF supplementation improved bone formation (p < 0.05), reduced bone resorption (p < 0.05), enhanced femoral bone mineral density and microarchitecture (p < 0.05), and upregulated osteocalcin, osterix, and Runx-2 expression (p < 0.05) of femur. LF upregulated 69 urinary metabolites. KEGG and pathway enrichment analyses of those urinary metabolites, and the Person’s correlation analyses among those urinary metabolites and bone status revealed that LF impacted on bone formation via regulatory comprehensive pathways including taurine and hypotaurine metabolism, arginine and proline metabolism, cyanoamino acid metabolism, nitrogen metabolism, nicotinate and nicotinamide metabolism, and fatty acid biosynthesis. The present study indicated the metabolomics is a useful and practical tool to elucidate the mechanisms by which LF augments bone mass formation in growing animals.

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“…Notably, these studies controlling for MSM status account for only 33% (N = 16) of the total studies (N = 48) comparing HIV+ to HIV− patients published to date [29, 50-54, 56-58, 60-64, 68, 76, 83-85, 88-100]. Several other studies variably controlled for MSM status but had no HIV-control group [15,30,32,34,38,54,66,67,69,[101][102][103][104][105][106][107][108]. Thus, the majority of published studies to date have been insufficiently controlled for the critical variable of MSM status, limiting interpretation of the data.…”

Section: Hiv and The Gut Microbiome: No Consistent Hiv-linked Dysbiosis Identified Msm Status As A Confoundermentioning

confidence: 99%

HIV, Sexual Orientation, and Gut Microbiome Interactions

2020

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Recent studies have raised interest in the possibility that dysbiosis of the gut microbiome (i.e., the communities of bacteria residing in the intestine) in HIV-infected patients could contribute to chronic immune activation, and, thus, to elevated mortality and increased risk of inflammation-related clinical diseases (e.g., stroke, cardiovascular disease, cancer, long-bone fractures, and renal dysfunction) found even in those on effective antiretroviral therapy. Yet, to date, a consistent pattern of HIV-associated dysbiosis has not been identified. What is becoming clear, however, is that status as a man who has sex with men (MSM) may profoundly impact the structure of the gut microbiota, and that this factor likely confounded many HIVrelated intestinal microbiome studies. However, what factor associated with MSM status drives these gut microbiota-related changes is unclear, and what impact, if any, these changes may have on the health of MSM is unknown. In this review, we outline available data on changes in the structure of the gut microbiome in HIV, based on studies that controlled for MSM status. We then examine what is known regarding the gut microbiota in MSM, and consider possible implications for research and the health of this population. Lastly, we discuss knowledge gaps and needed future studies.

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The Effects of Recombinant Human Lactoferrin on Immune Activation and the Intestinal Microbiome Among Persons Living with Human Immunodeficiency Virus and Receiving Antiretroviral Therapy

Cited by 21 publications

References 15 publications

Daily Dose of Bovine Lactoferrin Prevents Ethanol‐Induced Liver Injury and Death in Male Mice by Regulating Hepatic Alcohol Metabolism and Modulating Gut Microbiota

Daily Dose of Bovine Lactoferrin Prevents Ethanol‐Induced Liver Injury and Death in Male Mice by Regulating Hepatic Alcohol Metabolism and Modulating Gut Microbiota

Urinary Metabolic Profiling via LC-MS/MS Reveals Impact of Bovine Lactoferrin on Bone Formation in Growing SD Rats

HIV, Sexual Orientation, and Gut Microbiome Interactions

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