Protein research in millets: current status and way forward.

MAIN CONCLUSION: Millets' protein studies are lagging behind those of major cereals. Current status and future insights into the investigation of millet proteins are discussed. Millets are important small-seeded cereals majorly grown and consumed by people in Asia and Africa and are considered crops of future food security. Although millets possess excellent climate resilience and nutrient supplementation properties, their research advancements have been lagging behind major cereals. Although considerable genomic resources have been developed in recent years, research on millet proteins and proteomes is currently limited, highlighting a need for further investigation in this area. This review provides the current status of protein research in millets and provides insights to understand protein responses for climate resilience and nutrient supplementation in millets. The reference proteome data is available for sorghum, foxtail millet, and proso millet to date; other millets, such as pearl millet, finger millet, barnyard millet, kodo millet, tef, and browntop millet, do not have any reference proteome data. Many studies were reported on stress-responsive protein identification in foxtail millet, with most studies on the identification of proteins under drought-stress conditions. Pearl millet has a few reports on protein identification under drought and saline stress. Finger millet is the only other millet to have a report on stress-responsive (drought) protein identification in the leaf. For protein localization studies, foxtail millet has a few reports. Sorghum has the highest number of 40 experimentally proven crystal structures, and other millets have fewer or no experimentally proven structures. Further proteomics studies will help dissect the specific proteins involved in climate resilience and nutrient supplementation and aid in breeding better crops to conserve food security.

Drought resistance strategies in minor millets: a review.

MAIN CONCLUSION: The review discusses growth and drought-response mechanisms in minor millets under three themes: drought escape, drought avoidance and drought tolerance. Drought is one of the most prominent abiotic stresses impacting plant growth, performance, and productivity. In the context of climate change, the prevalence and severity of drought is expected to increase in many agricultural regions worldwide. Millets (coarse grains) are a group of small-seeded grasses cultivated in arid and semi-arid regions throughout the world and are an important source of food and feed for humans and livestock. Although minor millets, i.e., foxtail millet, finger millet, proso millet, barnyard millet, kodo millet and little millet are generally hardier and more drought-resistant than cereals and major millets (sorghum and pearl millet), understanding their responses, processes and strategies in response to drought is more limited. Here, we review drought resistance strategies in minor millets under three themes: drought escape (e.g., short crop cycle, short vegetative period, developmental plasticity and remobilization of assimilates), drought avoidance (e.g., root traits for better water absorption and leaf traits to control water loss), and drought tolerance (e.g., osmotic adjustment, maintenance of photosynthetic ability and antioxidant potential). Data from 'omics' studies are summarized to provide an overview of the molecular mechanisms important in drought tolerance. In addition, the final section highlights knowledge gaps and challenges to improving minor millets. This review is intended to enhance major cereals and millet per se in light of climate-related increases in aridity.

Impact of LAB Fermentation on the Nutrient Content, Amino Acid Profile, and Estimated Glycemic Index of Sorghum, Pearl Millet, and Kodo Millet.

INTRODUCTION: Millets, owing to their rich nutritional and low-to-moderate glycemic index values, are termed superfoods; however, some anti-nutritional factors, such as tannins, limit the absorption of micro and macronutrients. Non-thermal processing technologies, such as fermentation, can improve nutrient content and reduce these anti-nutritional factors. METHODS: The effect of a controlled submerged fermentation of whole grain sorghum, pearl millet, and dehusked Kodo millet using mixed lactic acid bacteria (LAB) culture in tofu whey-based media on the proximate, antioxidant, tannin content, vitamin B, amino acids profile and estimated glycemic index (eGI) of different millets were evaluated. RESULTS: The protein content (2-12.5%), carbohydrate content (2-13.6%), antioxidant activity (3-49%), vitamin B complex, amino acid profile (89-90%), and eGI of whole grain sorghum, pearl millet, and dehusked Kodo millet improved due to LAB-assisted submerged fermentation. In contrast, fat (4-15%), ash (56-67%), crude fiber (5-34%), minerals, tannin and resistant starch content decreased due to LAB fermentation. CONCLUSION: Controlled LAB fermentation can improve the nutritional quality of sorghum and millets while reducing anti-nutritional factors. This non-thermal process can be adopted industrially to produce more palatable and nutritionally superior millet products.

A comprehensive study on the impact of human hair fiber and millet husk ash on concrete properties: response surface modeling and optimization.

Revolutionizing construction, the concrete blend seamlessly integrates human hair (HH) fibers and millet husk ash (MHA) as a sustainable alternative. By repurposing human hair for enhanced tensile strength and utilizing millet husk ash to replace sand, these materials not only reduce waste but also create a durable, eco-friendly solution. This groundbreaking methodology not only adheres to established structural criteria but also advances the concepts of the circular economy, representing a significant advancement towards environmentally sustainable and resilient building practices. The main purpose of the research is to investigate the fresh and mechanical characteristics of concrete blended with 10-40% MHA as a sand substitute and 0.5-2% HH fibers by applying response surface methodology modeling and optimization. A comprehensive study involved preparing 225 concrete specimens using a mix ratio of 1:1.5:3 with a water-to-cement ratio of 0.52, followed by a 28 day curing period. It was found that a blend of 30% MHA and 1% HH fibers gave the best compressive and splitting tensile strengths at 28 days, which were 33.88 MPa and 3.47 MPa, respectively. Additionally, the incorporation of increased proportions of MHA and HH fibers led to reductions in both the dry density and workability of the concrete. In addition, utilizing analysis of variance (ANOVA), response prediction models were created and verified with a significance level of 95%. The models' R2 values ranged from 72 to 99%. The study validated multi-objective optimization, showing 1% HH fiber and 30% MHA in concrete enhances strength, reduces waste, and promotes environmental sustainability, making it recommended for construction.

Brown-top millet: an overview of breeding, genetic, and genomic resources development for crop improvement.

MAIN CONCLUSION: Brown-top millet is a lesser-known millet with a high grain nutrient value, early maturation, and drought tolerance that needs basic research to understand and conserve food security. Brown-top millet [Urochloa ramosa (L.)] is currently cultivated in some developing countries (especially in India) for food and fodder, although it is less known among the small millets. Like other millets, it contains macro- and micronutrients, vitamins, minerals, proteins, and fiber, all of which have rich health benefits. The nutritional importance and health benefits of brown-top millet are still unknown to many people due to a lack of awareness, wide cultivation, and research. Hence, this millet is currently overshadowed by other major cereals. This review article aims to present the nutritional, breeding, genetic, and genomic resources of brown-top millet to inform millet and other plant researchers. It is important to note that genetic and genomic resources have not yet been created for this millet. To date, there are no genomic and transcriptomic resources for brown-top millet to develop single nucleotide polymorphisms (SNP) and insertion/Deletions (InDels) for breeding studies. Furthermore, studies regarding nutritional significance and health benefits are required to investigate the exact nutritional contents and health benefits of the brown-top millet. The present review delves into the nutritional value and health advantages of brown-top millet, as supported by the available literature. The limitations of producing brown-top millet have been enumerated. We also cover the status of marker-assisted breeding and functional genomics research on closely related species. Lastly, we draw insights for further research such as developing omics resources and applying genome editing to study and improve brown-top millet. This review will help to start breeding and other molecular studies to increase the growth and development of this cereal.

Unlocking the potential of Kodo millet: reviving an indigenous super grain for tomorrow's nutrition.

Kodo millet (Paspalum scrobiculatum L.) is an underutilized crop that encompasses nutritional benefits and climate resilience, making it a viable option for future crop development with nutraceutical properties. The cultivation of this crop has ancient roots, where it was revered for its ability to thrive in times of famine and was a vital companion crop to rice. Dishes made with Kodo millet are highly palatable and can be easily integrated into mainstream rice-based dishes. Among all cereals, Kodo millet is distinguished by its gluten-free composition, high phosphorus content, and significant antioxidant potential, which contributes to a diet that may reduce cardiovascular disease risk. Often grown in rainfed zones by marginal farmers, Kodo millet is valued for its grain and fodder. This less demanding crop can tolerate both biotic and abiotic stress, allowing it to thrive in soils with low organic matter and with minimal inputs, making it an ideal dual-purpose crop for rainfed areas. Despite its nutritional and agricultural benefits, Kodo millet's popularity is hindered by challenges such as low yield, market demand, lodging at harvest, and poor dehulling recovery, which necessitate the development of high-yielding varieties through the latest breeding advancements. Systematic investment and concerted breeding efforts are essential to harness the full potential of this nutrient-dense crop. The absence of whole genome sequence for Kodo millet poses a barrier to uncovering novel genetic traits. Consequently, there is an imperative to establish a millet-based value chain that elevates these underutilized crops, shaping smart cropping patterns and enhancing nutritional profiles for sustainable diets. Accordingly, this review highlights the significance of Kodo millet and the impact of breeding to establish it as a smart food choice for the future.

The predominant lactic acid bacteria and yeasts involved in the spontaneous fermentation of millet during the production of the traditional porridge Hausa koko in Ghana.

Spontaneous fermentation of cereals like millet involves a diverse population of microbes from various sources, including raw materials, processing equipment, fermenting receptacles, and the environment. Here, we present data on the predominant microbial species and their succession at each stage of the Hausa koko production process from five regions of Ghana. The isolates were enumerated using selective media, purified, and phenotypically characterised. The LAB isolates were further characterised by 16S rRNA Sanger sequencing, typed using (GTG)5 repetitive-PCR, and whole genome sequencing, while 28S rRNA Sanger sequencing was performed for yeast identification. The pH of the millet grains ranged from mean values of 6.02-6.53 to 3.51-3.99 in the final product, depending on the processors. The mean LAB and yeast counts increased during fermentation then fell to final counts of log 2.77-3.95 CFU/g for LAB and log 2.10-2.98 CFU/g for yeast in Hausa koko samples. At the various processing stages, the counts of LAB and yeast revealed significant variations (p < 0.0001). The species of LAB identified in this study were Limosilactobacillus pontis, Pediococcus acidilactici, Limosilactobacillus fermentum, Limosilactobacillus reuteri, Pediococcus pentosaceus, Lacticaseibacillus paracasei, Lactiplantibacillus plantarum, Schleiferilactobacillus harbinensis, and Weissella confusa. The yeasts were Saccharomyces cf. cerevisiae/paradoxus, Saccharomyces cerevisiae, Pichia kudriavzevii, Clavispora lusitaniae and Candida tropicalis. The identification and sequencing of these novel isolates and how they change during the fermentation process will pave the way for future controlled fermentation, safer starter cultures, and identifying optimal stages for starter culture addition or nutritional interventions. These LAB and yeast species are linked to many indigenous African fermented foods, potentially acting as probiotics in some cases. This result serves as the basis for further studies into the technological and probiotic potential of these Hausa koko microorganisms.

The role of phenomics and genomics in delineating the genetic basis of complex traits in millets.

Millets, comprising a diverse group of small-seeded grains, have emerged as vital crops with immense nutritional, environmental, and economic significance. The comprehension of complex traits in millets, influenced by multifaceted genetic determinants, presents a compelling challenge and opportunity in agricultural research. This review delves into the transformative roles of phenomics and genomics in deciphering these intricate genetic architectures. On the phenomics front, high-throughput platforms generate rich datasets on plant morphology, physiology, and performance in diverse environments. This data, coupled with field trials and controlled conditions, helps to interpret how the environment interacts with genetics. Genomics provides the underlying blueprint for these complex traits. Genome sequencing and genotyping technologies have illuminated the millet genome landscape, revealing diverse gene pools and evolutionary relationships. Additionally, different omics approaches unveil the intricate information of gene expression, protein function, and metabolite accumulation driving phenotypic expression. This multi-omics approach is crucial for identifying candidate genes and unfolding the intricate pathways governing complex traits. The review highlights the synergy between phenomics and genomics. Genomically informed phenotyping targets specific traits, reducing the breeding size and cost. Conversely, phenomics identifies promising germplasm for genomic analysis, prioritizing variants with superior performance. This dynamic interplay accelerates breeding programs and facilitates the development of climate-smart, nutrient-rich millet varieties and hybrids. In conclusion, this review emphasizes the crucial roles of phenomics and genomics in unlocking the genetic enigma of millets.

Cold Plasma Treatment of Little Millet Flour: Impact on Bioactives, Antinutritional Factors and Functional Properties.

This study delves into the transformative effects of atmospheric cold plasma (CP) treatment on little millet flour (LMF), specifically exploring alterations in bioactive compounds, antinutritional factors, and functional properties. Foaming and emulsification properties experienced noteworthy enhancements with plasma treatment, manifesting in significant increases in foaming capacity (up to 51.47 ± 0.49%), foaming stability, emulsification ability, and emulsion stability (up to 47.02 ± 0.35%). The treatment also positively influenced water absorption index and swelling power. Antinutritional factors, including tannins and saponins, exhibited substantial reductions following plasma treatment. Saponin content, for instance, decreased by an impressive 58% after exposure to 20 kV for 20 min. Conversely, bioactive compounds such as phenolic content and antioxidant activity saw significant increases. Total phenolic content (TPC) rose from 527.54 ± 8.94 to 575.82 ± 3.58 mg GAE/100 g, accompanied by a remarkable 59% boost in antioxidant activity. Interestingly, plasma treatment did not exhibit a discernible effect on pasting properties. These findings collectively underscore the potential of atmospheric CP treatment as a novel and effective method for enhancing the functional and nutritional attributes of LMF, thereby opening new avenues for its application in food science and technology.

Long-term fertilization and manuring effects on the nexus between sulphur distribution and SOC in an Inceptisol over five decades under a finger millet-maize cropping system.

Our investigation revealed that alterations in sulphur (S) pools are predominantly governed by soil organic carbon (SOC), soil nitrogen (N), microbial biomass, and soil enzyme activities in sandy clay loam (Vertic Ustropept) soil. We employed ten sets of nutrient management techniques, ranging from suboptimal (50% RDF) to super-optimal doses (150% RDF), including NPK + Zn, NP, N alone, S-free NPK fertilizers, NPK + FYM, and control treatments, to examine the interrelation of S with SOC characteristics. Fourier-transform infrared (FT-IR) spectroscopy was utilized to analyze the functional groups present in SOC characterization across four treatments: 100% NPK, 150% NPK, NPK + FYM, and absolute control plots. Principal component analysis (PCA) was then applied to assess 29 minimal datasets, aiming to pinpoint specific soil characteristics influencing S transformation. In an Inceptisol, the application of fertilizers (100% RDF) in conjunction with 10 t ha-1 of FYM resulted in an increase of S pools from the surface to the subsurface stratum (OS > HSS > SO42--S > WSS), along with an increase in soil N and SOC. FT-IR spectroscopy identified cellulose and thiocyanate functional groups in all four plots, with a pronounced presence of carbohydrate-protein polyphenol, sulfoxide (S=O), and nitrate groups specifically observed in the INM plot. The PCA findings indicated that the primary factors influencing soil quality and crop productivity (r2 of 0.69) are SOC, SMBC, SMBN, SMBS, and the enzyme activity of URE, DHA, and AS. According to the study, the combined application of fertilizer and FYM (10 t ha-1) together exert a positive impact on sulphur transformation, SOC accumulation, and maize yield in sandy clay loam soil.

Major transcription factor families at the nexus of regulating abiotic stress response in millets: a comprehensive review.

Millets stand out as a sustainable crop with the potential to address the issues of food insecurity and malnutrition. These small-seeded, drought-resistant cereals have adapted to survive a broad spectrum of abiotic stresses. Researchers are keen on unravelling the regulatory mechanisms that empower millets to withstand environmental adversities. The aim is to leverage these identified genetic determinants from millets for enhancing the stress tolerance of major cereal crops through genetic engineering or breeding. This review sheds light on transcription factors (TFs) that govern diverse abiotic stress responses and play role in conferring tolerance to various abiotic stresses in millets. Specifically, the molecular functions and expression patterns of investigated TFs from various families, including bHLH, bZIP, DREB, HSF, MYB, NAC, NF-Y and WRKY, are comprehensively discussed. It also explores the potential of TFs in developing stress-tolerant crops, presenting a comprehensive discussion on diverse strategies for their integration.

Fermentation of millet bran with Bacillus natto: enhancement of bioactivity levels and the bioactivity of bran extract.

BACKGROUND: Millet bran (MB), a byproduct of millet production, is rich in functional components but it is underutilized. In recent years, researchers have shown that fermentation can improve the biological activity of cereals and their byproducts. This study used Bacillus natto to ferment millet bran to improve its added value and broaden the application of MB. The bioactive component content, physicochemical properties, and functional activity of millet bran extract (MBE) from fermented millet bran were determined. RESULTS: After fermentation, the soluble dietary fiber (SDF) content increased by 92.0%, the ß-glucan content by 164.4%, the polypeptide content by 111.4%, the polyphenol content by 32.5%, the flavone content by 16.4%, and the total amino acid content by 95.4%. Scanning electron microscopy revealed that the microscopic morphology of MBE changed from complete and dense blocks to loosely porous shapes after fermentation. After fermentation, the solubility, water-holding capacity, and viscosity significantly increased and the particle size decreased. Moreover, the glucose adsorption capacity (2.1 mmol g-1), glucose dialysis retardation index (75.3%), and α-glucosidase inhibitory (71.4%, mixed reversible inhibition) activity of the fermented MBE (FMBE) were greater than those of the unfermented MBE (0.99 mmol g-1, 32.1%, and 35.1%, respectively). The FMBE presented better cholesterol and sodium cholate (SC) adsorption properties and the adsorption was considered inhomogeneous surface adsorption. CONCLUSION: Fermentation increased the bioactive component content and improved the physicochemical properties of MBE, thereby improving its hypoglycemic and hypolipidemic properties. This study not only resolves the problem of millet bran waste but also encourages the development of higher value-added application methods for millet bran. © 2024 Society of Chemical Industry.

Morphology and chemical composition of Taiwan oil millet (Eccoilopus formosanus) epicuticular wax.

MAIN CONCLUSION: Taiwan oil millet has two types of epicuticular wax: platelet wax composed primarily of octacosanol and filament wax constituted essentially by the singular compound of octacosanoic acid. Taiwan oil millet (TOM-Eccoilopus formosanus) is an orphan crop cultivated by the Taiwan indigenous people. It has conspicuous white powder covering its leaf sheath indicating abundant epicuticular waxes, that may contribute to its resilience. Here, we characterized the epicuticular wax secretion in TOM leaf blade and leaf sheath using various microscopy techniques, as well as gas chromatography to determine its composition. Two kinds of waxes, platelet and filaments, were secreted in both the leaf blades and sheaths. The platelet wax is secreted ubiquitously by epidermal cells, whereas the filament wax is secreted by a specific cell called epidermal cork cells. The newly developed filament waxes were markedly re-synthesized by the epidermal cork cells through papillae protrusions on the external periclinal cell wall. Ultrastructural images of cork cell revealed the presence of cortical endoplasmic reticulum (ER) tubules along the periphery of plasma membrane (PM) and ER-PM contact sites (EPCS). The predominant wax component was a C28 primary alcohol in leaf blade, and a C28 free fatty acid in the leaf sheath, pseudopetiole and midrib. The wax morphology present in distinct plant organs corresponds to the specific chemical composition: platelet wax composed of alcohols exists mainly in the leaf blade, whereas filament wax constituted mainly by the singular compound C28 free fatty acids is present abundantly in leaf sheath. Our study clarifies the filament wax composition in relation to a previous study in sorghum. Both platelet and filament waxes comprise a protection barrier for TOM.

Effectiveness of Millet-Pulse-Groundnut Based Formulations in Improving the Growth of Pre-School Tribal Children in Telangana State, India.

A community-level nutritional intervention was implemented among tribal children (3 to 6 years of age) in Telangana, India. The one-year intervention involved six nutrient-rich formulations of millet-pulse-groundnut-based products suited to local taste preferences. Anthropometric measurements of height, weight, and mid-upper-arm circumference (MUAC) along with haemoglobin (Hb) levels were monitored at baseline and endline. The treatment group showed considerable gains in height (3.2 cm), weight (1.68 kg), and MUAC (0.33 cm) over the control group. The paired t-test indicated significant differences (p < 0.01) between the pre- and post-intervention anthropometric measurements. Positive shifts were observed in terms of wasting (WHZ; -1.2 ± 1.3 to -0.9 ± 1), stunting (HAZ; -1.8 ± 1.6 to -0.3 ± 1.3), and underweight (WAZ; -1.9 ± 1.2 to -0.7 ± 1) in the treatment group. The Hb levels in the treatment group also improved significantly from 9.70 ± 0.14 g/dL (moderately anaemic) to 11.08 ± 0.13 g/dL (non-anaemic). Post-intervention focus group discussions (FGDs) involving mothers and teachers confirmed these positive impacts. Thus, a nutritional intervention formulated using climate-resilient millets, pulses, and groundnuts promotes dietary diversity and improves the nutrition and health statuses of children.

Impact of milling on the nutrients and anti-nutrients in browntop millet (Urochloa ramosa) and its milled fractions: evaluation of their flour functionality.

BACKGROUND: Browntop millet has gained popularity in recent years owing to its nutritional superiority and health benefits. However, the usage of browntop millet flours as ingredients in composite flours and functional foods is constrained due to a lack of information regarding the grain composition and its flour functionality. Therefore, the distribution of nutrients, anti-nutrients in browntop millet milled fractions and their flour functionality was evaluated in comparison to whole grain flour. RESULTS: Bran fraction comprised the highest protein (13.7%) and fat contents (27%) among other fractions. Pearling of dehulled grains considerably reduced phytic acid, saponins and flatulence-causing oligosaccharides in pearled grain flours. Besides, this led to the enrichment of soluble fibre, minerals, phenolics and trypsin inhibitors in bran fraction. Milling also impacted flour functionality. Despite its lower water holding ability, dehulled grain flour exhibited significantly higher oil absorption capacity than whole grain flour due to the removal of fibre-rich hull fraction. Although emulsion (45.2%) and foaming capacities (12.5%) were superior in bran flour, foam stability was greater in pearled grain flours. CONCLUSION: These findings suggest the potential utilisation of browntop millet milled flours as ingredients in the development of distinct food formulations and as partial substitutes to wheat flour in confectionary and bakery products. © 2024 Society of Chemical Industry.

Prevention of high-fat-diet-induced obesity in mice by soluble dietary fiber from fermented and unfermented millet bran.

Obesity-related diabetes, cardiovascular disease, and hypertension pose many risks to human health. Thus, mice on a high-fat diet were gavaged with millet bran (unfermented/fermented) soluble dietary fiber (RSDF/FSDF, 500 mg·kg-1) for 10 weeks in current research, and then evaluated the various biological indicators. These findings revealed that RSDF and FSDF supplements could prevent fat synthesis by inhibiting sterol regulatory element-binding protein-1c gene expression. The RSDF supplements can also accelerate fat catabolism through enhanced the mRNA expression levels of adipose triglyceride lipase and peroxisome proliferator-activated receptor α. FSDF supplements can prevent obesity by decreasing 3-hydroxy-3-methyl-glutaryl-CoA reductase expression and increasing cholesterol 7α-hydroxylase expression. Moreover, FSDF also controls obesity development by lowering total cholesterol and low-density lipoprotein cholesterol levels in the blood, triglyceride, total cholesterol, and bile acid levels in the liver. Notably, FSDF supplements can promote Bacteroides and Prevotella propagation; excretive propionic acid binds to free fatty acid receptor 2/3 and then stimulates intestinal epithelial cells to generate glucagon-like-peptide-1 and peptide YY, which can reduce food and energy intake and ultimately prevent obesity. All evidence suggests that FSDF supplements play a crucial role in preventing obesity.

Biomolecular evidence for changing millet reliance in Late Bronze Age central Germany.

The Bronze Age of Central Europe was a period of major social, economic, political and ideological change. The arrival of millet is often seen as part of wider Bronze Age connectivity, yet understanding of the subsistence regimes underpinning this dynamic period remains poor for this region, in large part due to a dominance of cremation funerary rites, which hinder biomolecular studies. Here, we apply stable isotope analysis, radiocarbon dating and archaeobotanical analysis to two Late Bronze Age (LBA) sites, Esperstedt and Kuckenburg, in central Germany, where human remains were inhumed rather than cremated. We find that people buried at these sites did not consume millet before the Middle Bronze Age (MBA) (ca. 1600 BCE). However, by the early LBA (ca. 1300-1050 BCE) people consumed millet, often in substantial quantities. This consumption appears to have subsequently diminished or ceased around 1050-800 BCE, despite charred millet grains still being found in the archaeological deposits from this period. The arrival of millet in this region, followed by a surge in consumption spanning two centuries, indicates a complex interplay of cultural and economic factors, as well as a potential use of millet to buffer changes in aridity in a region increasingly prone to crop failure in the face of climate change today.

Comprehensive physiological, transcriptomic, and metabolomic analysis of the key metabolic pathways in millet seedling adaptation to drought stress.

Drought is one of the leading environmental constraints that affect the growth and development of plants and, ultimately, their yield and quality. Foxtail millet (Setaria italica) is a natural stress-resistant plant and an ideal model for studying plant drought resistance. In this study, two varieties of foxtail millet with different levels of drought resistance were used as the experimental material. The soil weighing method was used to simulate drought stress, and the differences in growth, photosynthetic physiology, metabolite metabolism, and gene transcriptional expression under drought stress were compared and analyzed. We aimed to determine the physiological and key metabolic regulation pathways of the drought-tolerant millet in resistance to drought stress. The results showed that drought-tolerant millet exhibited relatively stable growth and photosynthetic parameters under drought stress while maintaining a relatively stable level of photosynthetic pigments. The metabolomic, transcriptomic, and gene co-expression network analysis confirmed that the key to adaptation to drought by millet was to enhance lignin metabolism, promote the metabolism of fatty acids to be transformed into cutin and wax, and improve ascorbic acid circulation. These findings provided new insights into the metabolic regulatory network of millet adaptation to drought stress.